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The study of platelet microparticles and P-selectin expression in patients with the peripheral arterial diseases 外周血动脉疾病患者血小板微粒与p -选择素表达的研究
Pub Date : 2023-05-22 DOI: 10.17816/maj296568
A. I. Ermakov, L. Gaikovaya, O. Sirotkina, T. Vavilova
BACKGROUND: High platelet reactivity leads to the progression of atherosclerosis and its complications. Activated platelets adhere to the site of endothelium damage on the vessel wall and initiate the formation of an arterial thrombus, followed by acute ischemia of the organ. Biochemical and cellular marker such as platelet microvesicles and P-selectin can be analyzed using flow cytometry, which is based on a specific antigen-antibody interaction. Patients with peripheral arterial disease are at significantly greater risk of cardiovascular and cerebrovascular complications than individuals of the same age and sex. The use of antiplatelet agents is an important part of pathogenetic therapy and prevention of cardiovascular diseases and their complications. AIM: This study was to evaluate the level of platelet microparticles and P-selectin expression in patients with peripheral arterial disease receiving antiplatelet therapy. MATERIALS AND METHODS: The study included 49 people, which included three study groups: patients with obliterating disease of the arteries of the lower extremities (n = 14) on the background of long-term use (more than 14 days) of double (75 mg clopidogrel and 100 mg Acetylsalicylic acid) antiplatelet therapy, patients with COVID-19 (n = 15), who made up the positive control group in the determination of microparticles of platelet origin, and healthy volunteers (n = 20) without signs of acute respiratory disease, without a history of cardiovascular and thromboembolic episodes, not taking antiplatelet drugs. The functional activity of platelets was assessed by two methods: using light aggregometry and analysis of P-selectin expression on platelet surface by flow cytometry. The number of platelets microparticles in blood plasma was also determined using flow cytometry. RESULTS: A significant decrease in platelet aggregation was found in patients with peripheral arterial disease taking antiplatelet agents, compared with controls by used light aggregometry. Similar changes were obtained when analyzing the expression of P-selectin on platelets. A higher percentage of platelets microparticles with the CD9+CD41+ phenotype was found in patients with severe inflammation compared with peripheral arterial disease patients treated with antiplatelet agents and compared with the healthy controls. CONCLUSIONS: Thus, our study reflects the consistency of the results of three different laboratory tests in assessing the platelets reactivity in patients with the peripheral arterial diseases taking antiplatelet drugs.
背景:高血小板反应性可导致动脉粥样硬化及其并发症的进展。活化的血小板粘附在血管壁上内皮损伤的部位,引发动脉血栓的形成,随后引起器官的急性缺血。生化和细胞标志物,如血小板微泡和p -选择素可以使用流式细胞术分析,这是基于特异性抗原-抗体相互作用。外周动脉疾病患者发生心脑血管并发症的风险明显高于相同年龄和性别的个体。抗血小板药物的使用是心血管疾病及其并发症的病理治疗和预防的重要组成部分。目的:观察外周动脉疾病患者接受抗血小板治疗后血小板微粒水平及p -选择素的表达。材料与方法:本研究纳入49人,分为三个研究组:消灭疾病患者下肢的动脉(n = 14)长期使用的背景(超过14天)双(氯吡格雷75毫克和100毫克阿司匹林)抗血小板治疗,患者COVID-19 (n = 15),组成阳性对照组的微粒测定血小板来源、和健康志愿者(n = 20)没有急性呼吸道疾病的迹象,没有心血管和血栓栓塞事件的历史,未服用抗血小板药物。采用光聚集法和流式细胞术检测血小板表面p -选择素的表达。用流式细胞术测定血浆中血小板微粒的数量。结果:与对照组相比,使用抗血小板药物的外周动脉疾病患者血小板聚集明显降低。在分析p -选择素在血小板上的表达时,也得到了类似的变化。与接受抗血小板药物治疗的外周动脉疾病患者和健康对照组相比,在严重炎症患者中发现CD9+CD41+表型的血小板微粒百分比更高。结论:本研究反映了三种不同实验室检测方法评估外周血管疾病患者服用抗血小板药物后血小板反应性的一致性。
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引用次数: 0
Reducing of the respiratory effects of dizocilpine by recombinant interleukin-1β in experiment 重组白细胞介素-1β降低二唑西平呼吸作用的实验研究
Pub Date : 2023-05-22 DOI: 10.17816/maj133602
T. Tumanova, Vladimir A. Merkurjev, G. Danilova, V. Aleksandrov
BACKGROUND: For a deeper understanding of the pathogenesis of COVID-19, it is necessary to study the mechanisms that implement the influence of pro-inflammatory cytokines on the processes of regulation of the external respiratory system. In experiments on anesthetized rats, the effect of the pro-inflammatory cytokine interleukin-1 on the respiratory effects of dizocilpine (MK-801), which has an inhibitory effect on neurotransmitter systems involved in the control of the respiratory system, was studied. It was considered that, first of all, dizocilpine is a highly effective non-competitive NMDA-type glutamate receptor blocker. AIM: The objectives of the study were to identify the effect of the influence of dizocilpine on the parameters of the breathing pattern and to assess the degree of change in this effect when dizocilpine was administered against the background of an elevated systemic level of interleukin-1. MATERIALS AND METHODS: The study was performed on 24 anesthetized tracheostomy spontaneously breathing rats. To register the volume-time parameters of external respiration, a pneumotachographic technique was used. In the process of processing the obtained results, the value of the recorded parameter was determined immediately before the introduction of MK-801 and 1 min after its introduction RESULTS: At a dosage of 0.1 mg/kg, dizocilpine was found to cause a reversible short-term decrease in respiratory rate, tidal volume, and minute respiratory volume. It has been shown that this effect of dizocilpine does not appear after intravenous administration of interleukin-1 (at a dosage of 2 g/kg). The results obtained confirm the assumption about the effect of an elevated systemic level of interleukin-1 on the state of neurotransmitter systems involved in the control of respiration. CONCLUSIONS: Based on the correlation of the obtained results with the literature data, an assumption was made about a change in the state of NMDA-type glutamate receptors under the influence of pro-inflammatory cytokines, which may be one of the mechanisms of cardiorespiratory dysfunctions observed in a systemic inflammatory reaction accompanied by hypercytokinemia.
背景:为了更深入地了解COVID-19的发病机制,有必要研究促炎细胞因子对外呼吸系统调节过程的影响机制。在麻醉大鼠实验中,研究了促炎细胞因子白细胞介素-1对二唑西平(MK-801)呼吸作用的影响,二唑西平对参与呼吸系统控制的神经递质系统有抑制作用。认为,首先,二唑西平是一种高效的非竞争性nmda型谷氨酸受体阻滞剂。目的:本研究的目的是确定二唑西平对呼吸模式参数的影响,并评估在全身白细胞介素-1水平升高的背景下给予二唑西平时这种影响的变化程度。材料与方法:采用24只气管切开术麻醉自主呼吸大鼠进行实验。为了记录体外呼吸的体积-时间参数,使用了气相摄影技术。在处理所得结果的过程中,分别在MK-801引入前和引入后1分钟测定记录参数的值。结果:0.1 mg/kg的剂量下,二唑西平可引起呼吸频率、潮气量和分钟呼吸量的可逆性短期降低。研究表明,静脉注射白细胞介素-1(剂量为2g /kg)后,二唑西平的这种作用不会出现。所获得的结果证实了关于白细胞介素-1系统水平升高对参与呼吸控制的神经递质系统状态的影响的假设。结论:基于所得结果与文献数据的相关性,我们假设nmda型谷氨酸受体在促炎细胞因子的影响下状态发生变化,这可能是全身性炎症反应伴高细胞因子血症时出现心肺功能障碍的机制之一。
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引用次数: 0
Visualisation of kupffer cells in the rat liver with poly- and monoclonal antibodies against microglial-specific protein Iba-1 用抗小胶质细胞特异性蛋白Iba-1的多克隆和单克隆抗体观察大鼠肝脏中的kupffer细胞
Pub Date : 2023-05-22 DOI: 10.17816/maj133649
I. A. Nikitina, V. Razenkova, O. V. Kirik, D. Korzhevskii
BACKGROUND: A necessary attribute of any study, which is related to the cell biology of various structural components of the digestive tract, is the usage of modern immunohistochemical methods. One of the most difficult objects are resident liver macrophages, or Kupffer cells. This determines the high significance to develop a reliable approach for Kupffer cells visualization. AIM: The aim of the study was to develop a protocol for the immunohistochemical research of Kupffer cells in rat liver using two types of primary antibodies against Iba-1, and to analyze the advantages and disadvantages of this approach, taking into account the use of zinc-ethanol-formaldehyde as a fixative. MATERIALS AND METHODS: The study was carried out on liver samples of adult Wistar rats (n = 5). Goat polyclonal and rabbit monoclonal antibodies against calcium-binding protein Iba-1 were used for the ligh microscopy immunohistochemistry assay of resident liver macrophages. RESULTS: Using two types of antibodies it was shown by quantitative analysis that rabbit monoclonal antibodies most completely reveal Iba-1-immunopositive structures compared to goat polyclonal antibodies. Fixation with zinc-ethanol-formaldehyde made it possible to reveal Iba-1-immunopositive cells in all studied rat liver samples. CONCLUSIONS: Iba-1 immunohistochemistry using rabbit monoclonal antibodies was considered as the most optimal immunohistochemical approach. Fixation with zinc-ethanol-formaldehyde preserves the antigenic epitopes and allows the effective use of different antibodies.
背景:任何与消化道各种结构成分的细胞生物学相关的研究的一个必要属性是使用现代免疫组织化学方法。其中最困难的对象之一是常驻肝巨噬细胞,或库普弗细胞。这决定了开发一种可靠的库普弗细胞可视化方法的重要性。目的:本研究的目的是建立一种使用两种抗Iba-1的一抗对大鼠肝脏库普弗细胞进行免疫组化研究的方案,并在考虑到使用锌乙醇甲醛作为固定剂的情况下,分析该方法的优缺点。材料与方法:采用成年Wistar大鼠肝脏标本(n = 5),采用山羊和兔抗钙结合蛋白Iba-1单克隆抗体进行常驻肝巨噬细胞的光镜免疫组化检测。结果:两种抗体的定量分析表明,兔单克隆抗体比山羊多克隆抗体更能完全显示iba -1免疫阳性结构。用锌-乙醇-甲醛固定可以在所有研究的大鼠肝脏样本中显示iba -1免疫阳性细胞。结论:采用兔单克隆抗体进行Iba-1免疫组化是最理想的免疫组化方法。用锌-乙醇-甲醛固定保存抗原表位,并允许有效地使用不同的抗体。
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引用次数: 0
The activity of the outstanding histologist academician A.A. Zavarzin as the commissioner of the tomsk group of laboratories of the Institute of Experimental Medicine in the period of the Great Patriotic War 伟大卫国战争时期,杰出的历史学家院士A.A.扎瓦津作为实验医学研究所托木斯克组实验室委员的活动
Pub Date : 2023-05-22 DOI: 10.17816/maj120166
D. Korzhevskii, O. V. Kirik
Academician A.A. Zavarzin (18861945) the founder of evolutionary histology and the creator of tissue parallelism theory, is known as an outstanding neurohistologist and organizer of the Department of General Morphology of the All-Union Institute of Experimental Medicine (AIEM). During the Great Patriotic War (World War II) A.A. Zavarzin was evacuated to Tomsk as part of the laboratories of the central part of AIEM (Moscow) and the Leningrad branch of AIEM (Leningrad). Some information about his scientific work in Tomsk is presented in the historical literature, however, up to the present, his organizational activities as a commissioner have not been known. Based on information from the archive of the Institute of Experimental Medicine (St. Petersburg), including previously unpublished materials from orders on personnel for 1941 and 1945 and those for the Tomsk Group of AIEM, this article presents new facts about the life and scientific and organizational activities of Academician A.A. Zavarzin during the Great Patriotic War. In the period from 1943 to 1944, he headed the Tomsk group of laboratories of the A.M. Gorky All-Union Institute of Experimental Medicine the main scientific medical institution in the country, on the basis of which the USSR Academy of Medical Sciences was organized in 1945.
扎瓦津院士(1886 - 1945)是进化组织学的创始人和组织平行理论的创造者,是一位杰出的神经组织学家,也是全联合实验医学研究所(AIEM)一般形态学部门的组织者。在卫国战争(第二次世界大战)期间,A.A.扎瓦津被疏散到托木斯克,作为AIEM(莫斯科)中部实验室和AIEM(列宁格勒)列宁格勒分部的一部分。关于他在托木斯克的科学工作的一些信息是在历史文献中提出的,然而,到目前为止,他作为委员的组织活动还不为人所知。本文根据实验医学研究所(圣彼得堡)档案馆的资料,包括1941年和1945年的人事命令和AIEM托木斯克小组的以前未发表的材料,介绍了伟大卫国战争期间扎瓦津院士的生活、科学和组织活动的新事实。1943年至1944年期间,他领导A.M.托木斯克实验室小组高尔基全联盟实验医学研究所是苏联主要的科学医疗机构,苏联医学科学院于1945年在其基础上成立。
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引用次数: 0
The effect of prolonged emotional and pain stress on the expression of the bdnf gene in the brain of rats with contrast excitability of the nervous system 长时间情绪和疼痛应激对神经系统对比兴奋性大鼠脑内bdnf基因表达的影响
Pub Date : 2023-05-22 DOI: 10.17816/maj119980
I. Shalaginova, T. Zachepilo, N. Dyuzhikova
BACKGROUND: The neurotrophic factor BDNF performs important functions in synaptic plasticity and functional activity of neurons, involve in the stress response and the pathogenesis of post-stress disorders. The specificity of post-stress changes in the bdnf mRNA level due to genetically determined features of excitability of the nervous system has not been studied. AIM: To study the level of bdnf mRNA in the prefrontal cortex, hippocampus and amygdala of rats of two strains with contrasting excitability of the nervous system in normal condition and at different times after prolonged emotional and painful stress exposure (after 24 hours, 7, 24, 60 days). MATERIALS AND METHODS: The study was carried out on adult male rats of two strains with a different level of excitability of the nervous system (HT high threshold and LT low threshold of excitability). As a model of chronic stress, a long-term emotional and painful exposure according to Hecht was used. The bdnf mRNA level was determined using quantitative real-time PCR. Changes in the level of bdnf mRNA in the prefrontal cortex, hippocampus and amygdala of control and experimental groups of rats of two strains were studied at different time points (24 hours, 7, 24 days, 2 months) after prolonged emotional and painful stress exposure. RESULTS: It was found that in highly excitable LT rats, a decrease in the expression of the bdnf gene in the prefrontal cortex occurs 24 hours and persists up to 7 days after exposure, in the hippocampus 2 months after exposure. In rats of the low-excitable HT strain, the decrease in bdnf mRNA was not detected. CONCLUSIONS: In highly excitable LT rats, prolonged emotional and painful stress causes a decrease in the expression of the bdnf gene in the prefrontal cortex and hippocampus. In low-excitable rats of the HT strain, no significant decrease in the mRNA level of this neurotrophin was found in any of the studied brain regions. The possible association of this specificity of changes in the level of bdnf mRNA with a greater severity of post-stress anxiety-like behavior disorders in highly excitable rats compared with low-excitable ones is discussed.
背景:神经营养因子BDNF在神经元突触可塑性和功能活动中发挥重要作用,参与应激反应和应激后障碍的发病机制。由于神经系统兴奋性的遗传决定特征,应激后bdnf mRNA水平变化的特异性尚未研究。目的:研究正常状态和长时间情绪和痛苦应激暴露后(24小时、7、24、60天)不同时间神经系统兴奋性对比的两品系大鼠前额叶皮层、海马和杏仁核中bdnf mRNA的表达水平。材料与方法:选取两种不同神经系统兴奋性水平(HT高兴奋性阈值和LT低兴奋性阈值)的成年雄性大鼠进行研究。根据Hecht的说法,长期的情绪和痛苦暴露被用作慢性压力的模型。采用实时荧光定量PCR检测bdnf mRNA水平。研究两品系对照组和实验组大鼠在长时间情绪和疼痛应激后不同时间点(24小时、7天、24天、2个月)前额叶皮层、海马和杏仁核中bdnf mRNA水平的变化。结果:在高兴奋性LT大鼠中,暴露24小时后前额皮质bdnf基因表达下降,持续7天,暴露2个月后海马bdnf基因表达下降。在低兴奋性HT菌株大鼠中,未检测到bdnf mRNA的减少。结论:在高兴奋性LT大鼠中,长时间的情绪和疼痛应激可导致前额叶皮层和海马中bdnf基因的表达降低。在HT菌株的低兴奋大鼠中,在研究的任何脑区均未发现该神经营养因子mRNA水平的显著降低。与低兴奋大鼠相比,高兴奋大鼠应激后焦虑样行为障碍的严重程度可能与bdnf mRNA水平变化的特异性相关。
{"title":"The effect of prolonged emotional and pain stress on the expression of the bdnf gene in the brain of rats with contrast excitability of the nervous system","authors":"I. Shalaginova, T. Zachepilo, N. Dyuzhikova","doi":"10.17816/maj119980","DOIUrl":"https://doi.org/10.17816/maj119980","url":null,"abstract":"BACKGROUND: The neurotrophic factor BDNF performs important functions in synaptic plasticity and functional activity of neurons, involve in the stress response and the pathogenesis of post-stress disorders. The specificity of post-stress changes in the bdnf mRNA level due to genetically determined features of excitability of the nervous system has not been studied. \u0000AIM: To study the level of bdnf mRNA in the prefrontal cortex, hippocampus and amygdala of rats of two strains with contrasting excitability of the nervous system in normal condition and at different times after prolonged emotional and painful stress exposure (after 24 hours, 7, 24, 60 days). \u0000MATERIALS AND METHODS: The study was carried out on adult male rats of two strains with a different level of excitability of the nervous system (HT high threshold and LT low threshold of excitability). As a model of chronic stress, a long-term emotional and painful exposure according to Hecht was used. The bdnf mRNA level was determined using quantitative real-time PCR. Changes in the level of bdnf mRNA in the prefrontal cortex, hippocampus and amygdala of control and experimental groups of rats of two strains were studied at different time points (24 hours, 7, 24 days, 2 months) after prolonged emotional and painful stress exposure. \u0000RESULTS: It was found that in highly excitable LT rats, a decrease in the expression of the bdnf gene in the prefrontal cortex occurs 24 hours and persists up to 7 days after exposure, in the hippocampus 2 months after exposure. In rats of the low-excitable HT strain, the decrease in bdnf mRNA was not detected. \u0000CONCLUSIONS: In highly excitable LT rats, prolonged emotional and painful stress causes a decrease in the expression of the bdnf gene in the prefrontal cortex and hippocampus. In low-excitable rats of the HT strain, no significant decrease in the mRNA level of this neurotrophin was found in any of the studied brain regions. The possible association of this specificity of changes in the level of bdnf mRNA with a greater severity of post-stress anxiety-like behavior disorders in highly excitable rats compared with low-excitable ones is discussed.","PeriodicalId":342669,"journal":{"name":"Medical academic journal","volume":"53 9","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"120857580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of beta-D-glucan on survival and hematopoietic parameters of mice after exposure to X-rays - d -葡聚糖对x射线照射后小鼠存活和造血参数的影响
Pub Date : 2023-05-22 DOI: 10.17816/maj114742
E. V. Murzina, G. A. Sofronov, A. Simbirtsev, N. Aksenova, G. G. Zagorodnikov, O. M. Veselova, Nataly-Adelgeida Zhirnova, E. V. Dmitrieva, Nicolay A. Klimov, Evgeniy V. Vorobeychikov
BACKGROUND: There is a high need for drugs to reduce the side effects of radiation exposure on people in extreme, military, marine, space medicine, at nuclear facilities, in hematology and oncology. AIM: To evaluate the antiradiation efficacy of beta-D-glucan derived from Oyster mushroom (Pleurotus ostreatus) after total body irradiation of mice in terms of survival and hematopoiesis. MATERIALS AND METHODS: The study was conducted on a mouse model of the acute radiation hematopoietic syndrome caused by exposure to X-rays. Radioprotective effect of intragastrically administered beta-D-glucan derived from Pleurotus ostreatus at a dose of 500 mg/kg was studied. The parameters of the 30-day survival of irradiated mice were analyzed using the KaplanMeyer method. Dose reduction factor of X-ray radiation was calculated to evaluate the radiomodifying effect. The hematopoiesis was assessed by the endogenous colony formation test and hematological parameters in irradiated mice. Statistical analysis was performed using the Statistica 8.0 software. RESULTS: The antiradiation efficacy of orally administered beta-D-glucan has been shown. DRF was 1.16 when the drug was administered 0.5 hours before irradiation and 1.06 during therapeutic use (after 1 or 2 hours). There was a decrease in weight loss in lethally irradiated mice and its faster recovery. Single oral administration of beta-D-glucan at a dose of 500 mg/kg stimulated the growth of splenic endogenous colony-forming units in mice on day 9 after total body irradiation at doses of 7 and 7.8 Gy, contributed to a decrease in the severity of leukopenia and thrombocytopenia. The antiradiation effect of beta-D-glucan was associated with an increase in the viability of bone marrow stem cells and a faster restoration of hematopoiesis. CONCLUSIONS: The results obtained indicate the possibility of using beta-D-glucan from P. ostreatus both before irradiation to increase the radioresistance and for early therapy of the hematopoietic syndrome of acute radiation sickness.
背景:在极端、军事、海洋、空间医学、核设施、血液学和肿瘤学领域,迫切需要药物来减少辐射暴露对人体的副作用。目的:评价平菇(Pleurotus ostreatus)中提取的β - d -葡聚糖对小鼠全身辐照后的生存和造血功能的影响。材料与方法:采用x射线致急性放射性造血综合征小鼠模型进行研究。研究了以500 mg/kg剂量灌胃平菇β - d -葡聚糖的辐射防护作用。采用kaplan - meyer法分析辐照小鼠30天存活参数。计算x射线辐照剂量减少因子,评价其辐照改性效果。用内源性菌落形成试验和血液学指标评价辐照小鼠的造血功能。采用Statistica 8.0软件进行统计分析。结果:口服β - d -葡聚糖具有抗辐射作用。辐照前0.5小时给药时DRF为1.16,治疗期间(1或2小时后)DRF为1.06。受致命辐射的小鼠体重减轻,恢复速度更快。单次口服500 mg/kg剂量的β - d -葡聚糖可刺激7 Gy和7.8 Gy全身照射后第9天小鼠脾内源性集落形成单位的生长,减轻白细胞减少和血小板减少的严重程度。β - d -葡聚糖的抗辐射作用与骨髓干细胞活力的增加和造血功能的更快恢复有关。结论:本研究结果提示,在放疗前使用山参β - d -葡聚糖可提高急性放射病造血综合征患者的放射抵抗力,并可用于早期治疗。
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引用次数: 0
The concept of endothelial transcytosis as a theoretical prerequisite for the development of prevention and treatment of atherosclerosis 内皮细胞吞噬的概念是动脉粥样硬化预防和治疗发展的理论前提
Pub Date : 2023-05-22 DOI: 10.17816/maj321958
N. S. Parfenova, D. Tanyanskiy
This part of the review focuses on the proposed involvement of the gut microbiota in the realization of the genetic risk of multiple sclerosis, the formation of the intestinal microbiome in early life, and provides data supporting the hypothesis that aberrant formation of the intestinal microbiota in early life may be a predisposing factor to multiple sclerosis.
本部分综述的重点是肠道微生物群参与多发性硬化症遗传风险的实现,以及生命早期肠道微生物群的形成,并提供数据支持早期肠道微生物群异常形成可能是多发性硬化症易感因素的假设。
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引用次数: 0
Experimental model of acute blood loss using rats for screening evalution of non-specific activity of infusion solutions 大鼠急性失血实验模型筛选评价输液液的非特异性活性
Pub Date : 2023-02-01 DOI: 10.17816/maj109574
I. Shperling, Aleksey V. Krupin, N. Arokina, O. Rogov
BACKGROUND: In accordance with the current regulations, preclinical evaluation of the effectiveness of plasma substitutes for acute blood loss is carried out mainly on large laboratory animals (dogs, pigs) using a wide range of methods for assessing the structural and functional state of organs and systems of a biological object. It requires large expenditure of material resources and time, which is impractical at the stage of screening the effectiveness of newly developed infusion agents. In this regard, an urgent task is to develop a standardized model of acute blood loss on small laboratory animals for screening evaluation of the specific activity of infusion solutions with a subsequent research involving large laboratory animals. It is advisable to use laboratory rats as a biological object as they are the most suitable of the group of small laboratory animals for similarity of physiological laboratory indicators with humans. AIM: To develop a model of acute blood loss using small laboratory animals for screening evaluation of specific infusion solution activity. MATERIALS AND METHODS: Experiments were carried out on rats of the Vistar line with a weight of 330 41 g. The animals were divided into 3 groups: 1 experimental (20 individuals with acute blood loss simulation without treatment), 2 experimental (20 individuals with acute blood loss simulation and its replacement with Rheopolyglucin), intact (10 individuals without modeling of blood loss). The study design included: general anesthesia (intramuscular injection Zoletil 100 and Xylazin 2% in a ratio of 1 : 5 at the rate of 0.01 ml/kg of weight), catheterization of the femoral artery followed by controlled hardware exfusion of blood at a rate of 0.5 ml/min until the establishment of persistent (for 2 minutes) arterial hypotension; hardware synchronous monitoring of mean arterial pressure (MAP) (by direct tonometry through the contralateral femoral artery); calculation of the percentage of blood loss from the estimated circulating blood volume (CBV) equal to 5% of the animals weight; heart rate (HR) (by electrocardiogram) during the first three hours after blood exfusion. In its capacity as a test drug Rheopolyglucin, which was administered through an arterial femoral catheter immediately after blood exfusion in volume and speed, equal to volume and speed of exfusion, was used. Additionally, for a comprehensive assessment of the mechanisms of maintaining hemodynamic parameters individual dynamic calculated indicators for each individual are proposed: the reduced shock volume of blood and the infusion efficiency indicator. RESULTS: All rats in the experimental group died, 25% of which 1720 minutes after blood exfusion, 75% in range from 45 to 90 minutes. Rheopoliglyukin infusion reduced the death of animals by up to 35% and delayed the average death time to 4555 minutes. A single exfusion of blood in rats resulted in loss of 79 ml of blood (4651% of circulating blood volume), which was a
背景:根据现行法规,血浆代用品治疗急性失血的有效性的临床前评估主要是在大型实验动物(狗、猪)身上进行的,使用多种方法来评估生物对象的器官和系统的结构和功能状态。这需要花费大量的物力和时间,这在筛选新开发的输液剂的有效性阶段是不切实际的。在这方面,当务之急是建立一个标准化的小实验动物急性失血模型,以筛选评估输液溶液的比活性,并在随后的大型实验动物研究中进行。建议使用实验大鼠作为生物学对象,因为它们是小型实验动物群中最适合与人类生理实验室指标相似的动物。目的:建立小动物急性失血模型,筛选评价输注液特异性活性。材料与方法:实验对象为Vistar系大鼠,体重330 - 41 g。将大鼠分为3组:1组(模拟急性失血20只,未经处理),2组(模拟急性失血20只,用流变葡聚糖替代),完整组(不模拟失血10只)。研究设计包括:全身麻醉(以0.01 ml/kg体重,以1:5的比例肌肉注射唑来替尔100和噻嗪2%),股动脉插管后以0.5 ml/min的速度有控制的硬体放血,直到建立持续(2分钟)动脉低血压;硬体同步监测平均动脉压(MAP)(通过对侧股动脉直接测压);从相当于动物体重5%的估计循环血容量(CBV)中计算失血量百分比;血流后3小时内心率(HR)(心电图)。流变葡聚糖作为试验药物,在血液排出后立即通过动脉股导管给药,其体积和速度与排出量和速度相等。此外,为了全面评估维持血流动力学参数的机制,我们提出了每个个体的单独动态计算指标:减少的血休克量和输注效率指标。结果:实验组大鼠全部死亡,其中25%在放血后1720分钟死亡,75%在45 ~ 90分钟死亡。Rheopoliglyukin输注可使动物死亡率降低35%,平均死亡时间延迟至4555分钟。大鼠单次放血导致血液损失79毫升(循环血容量的4651%),并伴有平均动脉压和心率下降。这些指标的增加体现了对循环血容量减少的补偿,包括输液。代偿无效的一个标志是平均动脉压随着心率的动态增加而轻微升高。研究证明,计算指标(给定的脑卒中血容量和输注效率指标)值的增加是有效补偿血流动力学疾病的基准,包括输注血流动力学药物的结果。结论:采用计算血休克减少量和输注效率指数的急性失血模型评价输注液在急性失血中的比活性是可取的。
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引用次数: 0
Mytilus edulis hydrolysate enhances proliferation and protects endothelial cells against hypochlorous acid-induced oxidative stress 紫贻贝水解液促进细胞增殖,保护内皮细胞免受次氯酸诱导的氧化应激
Pub Date : 2023-02-01 DOI: 10.17816/maj114811
E. Starikova, J. Mammedova, O. Porembskaya
BACKGROUND: Endothelial dysfunction underlies the pathogenesis of many socially significant diseases. The search for new original drugs for the treatment of this condition remains an important scientific and practical task. Anti-inflammatory, anticoagulant and antioxidant effects of bivalve mollusks from the family of mussels (Mytilus edulis) hydrolysate and its derivatives have been described in different model systems. AIM: The purpose of this study was to investigate the effect of M. edulis hydrolysate on the functional activity of EA.hy926 endothelial cell line. MATERIALS AND METHODS: The viability and metabolic activity of endothelial cells were studied in MTT-test. To investigate the proliferative activity, a test with staining of cells with crystal violet dye was used. The ability of the preparation to neutralize the toxic effect of HOCl and H2O2 was evaluated using fluorescent dyes and flow cytometry. RESULTS: It was found that the preparation did not have cytotoxicity and significantly increased the proliferation of endothelial cells in dilutions from 1:10 to 1:60. The preparation had a neutralizing effect against HOCl, and in all the studied dilutions significantly increased the viability of the endothelium. The preparation was not effective against H2O2, and increased H2O2 toxic effect in the maximal studied concentration. At the same time, the anti-inflammatory effect of M. edulis hydrolysate was not confirmed in this model system. The preparation had no effect on the IL-8 production and adhesion molecule CD54 (ICAM-1) and tissue factor CD146 the expression. CONCLUSIONS: The preparation of M. edulis hydrolysate enhances the proliferation of endothelial cells and is able to neutralize HOCl toxic effects.
背景:内皮功能障碍是许多社会重大疾病的发病机制的基础。寻找治疗这种疾病的新药仍然是一项重要的科学和实际任务。贝科(Mytilus edulis)水解产物及其衍生物的双壳类软体动物的抗炎、抗凝血和抗氧化作用已在不同的模型系统中被描述。目的:研究毛竹水解液对EA.hy926内皮细胞功能活性的影响。材料与方法:采用mtt法研究内皮细胞的活力和代谢活性。用结晶紫染色法观察细胞的增殖活性。采用荧光染料和流式细胞术评价该制剂对HOCl和H2O2的中和毒性作用。结果:该制剂在1:10 ~ 1:60稀释范围内无细胞毒性,内皮细胞增殖明显增加。该制剂对HOCl有中和作用,在所有稀释浓度下均能显著提高内皮细胞的活力。该制剂对H2O2无抑制作用,且在最大浓度下H2O2毒性作用增强。同时,在该模型系统中,未证实毛蕊支杆菌水解物的抗炎作用。该制剂对IL-8的产生及粘附分子CD54 (ICAM-1)和组织因子CD146的表达无影响。结论:毛竹水解液的制备能增强内皮细胞的增殖,并能中和HOCl的毒性作用。
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引用次数: 0
The difficult years of Leon Abgarovich Orbeli: 140th anniversary of his birth 莱昂·阿加洛维奇·奥尔贝利的艰难岁月:他诞辰140周年
Pub Date : 2023-02-01 DOI: 10.17816/maj115043
E. Zakharova
L.A. Orbeli was one of the outstanding Russian physiologists, who at different times worked in the Department of Physiology of the Imperial Institute of Experimental Medicine under I.P. Pavlov and in St. Petersburg Marine Hospital, headed the Department of Evolutionary Physiology of the All-Union Institute of Experimental Medicine and Biostation in Koltushi (later on the Institute of Evolutionary Physiology and Pathology of Higher Nervous Activity of USSR Academy of Medical Sciences). During the Stalinist repressions he actively defended his fellow scientists, petitioning for their release. How many people were saved by L.A. Orbeli during the Stalinist terror, no one knows today. Abgar Leonovich (15.05.193920.12.2022), grandson of Leon Abgarovich, public figure and scientist, estimates that he saved at least a hundred people. Among those saved was the future Nobel Prize winner for physiology or medicine, Konrad Lorenz. Thanks to Leon Abragovichs intercession, E.M. Kreps trial for counterrevolutionary activities ended with 5 years in a labour camp, and not the highest punishment for the scientist. Thanks to him, Kreps was able to return to his scientific activities. Such activity could not remain unpunished and after the Pavlov session Orbeli was dismissed from all posts, but in 1956 he became Director of the I.M. Sechenov Institute of Evolutionary Physiology. I.M. Sechenov Institute of Evolutionary Physiology, which he headed until his death in 1958. L.A. Orbeli was one of the first native humanist, for whom humanist activity was not less important than scientific. The article is based on report of senior researcher of FGBNU IEM E.T. Zakharova Orbeli and his time, made in Academy of Sciences (SPb, Universitetskaya Embankment, 5) 07.07.2022 at the workshop dedicated to memory of academician L.A. Orbeli, timed to 140th anniversary since his birth.
l.a Orbeli是杰出的俄罗斯生理学家之一,他曾在巴甫洛夫领导下的帝国实验医学研究所生理学系和圣彼得堡海洋医院工作过,担任科尔图西全联盟实验医学和生物站进化生理学系主任(后来是苏联医学科学院高级神经活动进化生理和病理研究所)。在斯大林主义镇压期间,他积极为他的科学家同行辩护,为他们的获释请愿。在斯大林恐怖时期,L.A. Orbeli救了多少人,今天没有人知道。公众人物和科学家Leon Abgarovich的孙子Abgar Leonovich(15.05.193920.12.2022)估计他至少救了100人。其中包括后来的诺贝尔生理学或医学奖得主康拉德·洛伦兹。由于Leon abragovich的调停,E.M. Kreps对反革命活动的审判以劳改营的5年结束,这并不是对这位科学家的最高惩罚。多亏了他,克雷普斯才能回到他的科学活动中去。这样的活动不能不受到惩罚,在巴甫洛夫会议之后,奥尔贝利被解除了所有职务,但在1956年,他成为了谢切诺夫进化生理学研究所的主任。谢切诺夫进化生理学研究所,他领导该研究所直到1958年去世。L.A. Orbeli是最早的本土人文主义者之一,对他来说,人文活动的重要性不亚于科学。本文基于FGBNU IEM高级研究员E.T. Zakharova Orbeli的报告及其时间,该报告于2022年7月7日在科学院(SPb, Universitetskaya Embankment, 5)在纪念L.A. Orbeli院士的研讨会上发表,恰逢他诞辰140周年。
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