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Impaired Expression of Mu- and Kappa-Opioid Receptor mRNA in the Midbrain of Rats with Prenatal Alcohol Intoxication 产前酒精中毒大鼠中脑Mu-和kappa -阿片受体mRNA表达受损
Pub Date : 2022-12-12 DOI: 10.33647/2074-5982-18-4-112-122
V. Kokhan, P. Anokhin, E. P. Pakhlova, N. Sarycheva, I. Shamakina
Disruption of normal epigenetic reprogramming during the prenatal period under the influence of exogenous factors affects fetus development and adult phenotype formation. The mechanisms through which determinants, such as maternal alcohol intake, contribute to the formation of an alcohol-vulnerable phenotype later in life still remain unclear. In this paper, we suggest that alteration in the reinforcing properties of ethanol in prenatally alcohol-exposed subjects may be associated with transcriptional dysregulation of the brain opioid receptor genes. We compared voluntary alcohol intake and levels of mRNA coding for μ- (MOP) and κ-opioid (KOP) receptors in the mesolimbic areas of adult male offspring of the female Wistar rats having received 10% ethanol as the only source of liquid throughout pregnancy or water (control). We found that prenatally alcohol exposed rats had higher alcohol preference on PND60 (free-choice paradigm) and lower mRNA expression for both MOP and KOP in the midbrain compared to the control. This suggests a potential link between prenatal alcohol, dysfunction of the brain opiate system and adult vulnerability for alcohol use disorder.
在外源因素的影响下,产前正常表观遗传重编程的中断会影响胎儿发育和成人表型的形成。决定因素(如母亲酒精摄入量)在生命后期形成酒精易感表型的机制仍不清楚。在这篇论文中,我们认为在产前酒精暴露的受试者中,乙醇增强特性的改变可能与脑阿片受体基因的转录失调有关。我们比较了雌性Wistar大鼠成年雄性后代的自愿酒精摄入量和中边缘区μ- (MOP)和κ-阿片样物质(KOP)受体mRNA编码水平,雌性Wistar大鼠在怀孕期间只饮用10%乙醇或水(对照组)。我们发现,与对照组相比,产前酒精暴露大鼠对PND60(自由选择范式)有更高的酒精偏好,中脑MOP和KOP的mRNA表达较低。这表明产前酒精、大脑阿片系统功能障碍和成人酒精使用障碍之间存在潜在联系。
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引用次数: 0
Ultrastructural Characteristics of Axodendritic and Axosomatic Synapses in the Orbitofrontal Cortex of White Laboratory Rats Associated with Low-Protein Food after Acute Sound Exposure 急性声音暴露后低蛋白食物对实验鼠眼窝额叶皮层轴突突触和轴躯体突触超微结构的影响
Pub Date : 2022-12-12 DOI: 10.33647/2074-5982-18-4-94-101
M. Sultanly
This paper investigates the state of axodendritic (ADS) and axosomatic (ASS) synapses in orbitofrontal cortex (OFC) layers I-IV of adult white laboratory rats associated with balanced and low-protein food after acute sound exposure. Experiments were performed on 64 white non-linear sexually mature laboratory male rats weighing 180–230 g (eight intact, 56 experimental). After a continuous call with an intensity of 120 db for 120 seconds, 56 rats were divided into two groups: those receiving balanced (control – 28) and low-protein food (basic – 28). Each of these two groups was divided into two subgroups: stress-resistant (12 animals in each) and stress-unstable animals (16 animals in each). Water intake was unlimited. The animals were removed from the experiment on the 10th, 20th, 30th, and 40th day after sound exposure. Along with histological and immunohistochemical analysis, the samples of OFC layers I–IV were studied by transmission electron microscopy. Electron microscopic changes in the structure of ADS and ASS were found in all OFC layers. Violations of the fine structure of both the presynaptic and postsynaptic poles were noted. The maximum severity of ultrastructural changes was observed in the ADS of the surface (I, molecular), outer granular (II), pyramidal (III), and inner granular (IV) OFC layers. ASS disorganization was noted mainly in contacts, the postsynaptic pole of which was formed by the bodies of small pyramidal neurons of layer III, as well as pyramidal and stellate neurons of layer IV of the OFC. During all periods of observation, violations of fine organization were most pronounced in stress-unstable animals of the main experimental group, especially on the 10th and 20th day after exposure. Acute sound exposure initiates disturbances in the fine organization of axodendritic and axosomatic synapses in OFC layers I–IV of white laboratory rats. Focal destruction of a part of the noted synapses in rats with a low-protein diet after acute auditory stress is irreversible.
本文研究了平衡和低蛋白食物对成年白实验大鼠急性声音暴露后眼眶额叶皮质(OFC) I-IV层轴突突触(ADS)和轴体突触(ASS)的影响。实验对象为64只体重180 ~ 230 g的非线性性成熟实验室雄性大鼠(完整大鼠8只,实验大鼠56只)。在持续120秒120分贝强度的叫声后,56只大鼠被分成两组:接受平衡食物(对照组- 28)和低蛋白食物(基本- 28)。这两组中的每一组又分为两个亚组:抗压力动物(每组12只)和压力不稳定动物(每组16只)。水的摄入量是无限的。动物在声音暴露后第10、20、30、40天退出实验。结合组织学和免疫组织化学分析,透射电镜对OFC I-IV层样品进行了研究。在所有OFC层中均发现了ADS和ASS结构的电镜变化。突触前和突触后两极的精细结构都被破坏了。超微结构变化最严重的是表面(I,分子)、外颗粒(II)、锥体(III)和内颗粒(IV) OFC层的ADS。突触失序主要发生在接触区,其突触后极由OFC第3层小锥体神经元体以及OFC第4层锥体和星状神经元体构成。在所有观察期内,主实验组应激不稳定动物的精细组织破坏最为明显,特别是在暴露后第10天和第20天。急性声暴露可引起大鼠OFC I-IV层轴突突触和轴体突触精细组织的紊乱。低蛋白饮食对大鼠急性听觉应激后部分突触的局部破坏是不可逆的。
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引用次数: 0
Blockade of Rabbit Cardiomyocyte Calcium Channels Restores the Activity of Enzyme-Substrate Complexes of the Respiratory Chain in a Model of Vibration-Mediated Hypoxia 在振动介导的缺氧模型中,阻断兔心肌细胞钙通道恢复呼吸链酶-底物复合物的活性
Pub Date : 2022-12-11 DOI: 10.33647/2074-5982-18-4-63-73
V. V. Vorobieva, O. S. Levchenkova, P. Shabanov
The effect of nifedipine, a calcium channel blocker (CCB), at a dose of 7.5 mg/kg on the energy metabolism of rabbit cardiomyocytes was evaluated in a vibration-mediated model of cellular hypoxia (56 sessions of vibration 44 Hz, amplitude 0.5 mm). The energy metabolism of native heart mitochondria in a 30% tissue homogenate was assessed using a polarographic method, by recording the rate of oxygen uptake by mitochondria at 37°C in 1 ml of a saline incubation medium, equilibrated with atmospheric oxygen. In the animals exposed to vibration against the background of CCB, the rate of endogenous respiration (Ve) remained at the level of intact animals, with the amytal sensitivity increasing by 39% (p<0.05) and the malonate sensitivity decreasing by 40% (p<0.05). The malate oxidase activity at rest increased, and hyperactivation of the endogenous succinic acid oxidation system decreased as compared to the indices of the animals exposed to vibration without pharmacological protection. The observed results indicate the cardioprotective effect of nifedipine, which prevented the development of cardiomyocyte necrosis.
采用振动介导的细胞缺氧模型(振动56次,频率44 Hz,振幅0.5 mm),研究了7.5 mg/kg剂量硝苯地平对兔心肌细胞能量代谢的影响。采用极谱法评估天然心脏线粒体在30%组织匀浆中的能量代谢,方法是在37°C下,在1ml生理盐水培养液中记录线粒体的摄氧量,并与大气氧气平衡。在CCB背景下振动暴露的动物,内源性呼吸速率(Ve)保持在正常动物水平,戊醛敏感性提高39% (p<0.05),丙二酸敏感性降低40% (p<0.05)。与无药物保护的振动组相比,静息时苹果酸氧化酶活性增加,内源性琥珀酸氧化系统的超激活降低。结果表明硝苯地平对心肌细胞坏死具有明显的保护作用。
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引用次数: 1
Evaluation of the Efficiency of Phenol-Containing Complexes Extracted from Different Parts of Sorbus Aucuparia L. in an Oncological Experiment 荆芥不同部位含酚配合物在肿瘤实验中的作用评价
Pub Date : 2022-12-11 DOI: 10.33647/2074-5982-18-4-74-85
O. Rybalkina, T. Razina, E. A. Kiseleva, G. I. Kalinkina, N. V. Isaikina, E. Zueva, V. V. Zhdanov
Mountain ash (Sorbus aucuparia L.) is a prominent representative of phenolic medicinal plants. A widespread and cultivated plant, it has a sufficient raw material base not only of fruits, but also of other parts of the plant (leaves, flowers); it is a promising source of biologically active complexes for the development of new medical drugs. In the work, the content of the main groups of phenolic compounds in plant extracts from fruits, leaves and flowers of S. aucuparia L. was determined. Extracts were obtained using the original technology with acidified 95% ethanol. The content of the sum of phenolic compounds was determined, as well as the content of anthocyanins, flavonoids, phenolic acids, tannins. The effect of these phenol-containing complexes on the development of transplanted tumors (Lewis lung carcinoma, lung cancer-67) and the effectiveness of cyclophosphane treatment were studied. It was revealed that the use of plant complexes leads to a significant inhibition of the development of metastases in the lungs, as well as an increase in the antitumor and anti-metastatic activity of cyclophosphane in combined treatment. The new data obtained are of interest for further study of these phenol-containing complexes in order to create drugs based on them to increase the effectiveness of chemotherapy for malignant neoplasms.
山灰(Sorbus aucuparia L.)是酚类药用植物的杰出代表。作为一种广泛种植的植物,它不仅有果实,而且有植物的其他部分(叶、花)的充足原料基础;它是一种很有前途的生物活性配合物的来源,可用于开发新的药物。测定了金针桃果实、叶片和花的提取物中主要酚类化合物的含量。采用原始工艺,酸化95%乙醇提取提取物。测定了其总酚类化合物的含量,以及花青素、黄酮类、酚酸、单宁的含量。研究了这些含酚复合物对移植肿瘤(Lewis肺癌、肺癌)发展的影响以及环磷酰胺治疗的效果。结果表明,使用植物复合物可显著抑制肺转移的发展,并且在联合治疗中增加环磷酰胺的抗肿瘤和抗转移活性。所获得的新数据对于进一步研究这些含酚复合物,以创造基于它们的药物来提高恶性肿瘤化疗的有效性具有重要意义。
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引用次数: 0
Content of Biologically Active Substances in the Musk of Siberian Musk Deer Depending on Food Spectrum of Animal Nutrition 基于动物营养食物谱的西伯利亚麝麝香中生物活性物质含量研究
Pub Date : 2022-12-11 DOI: 10.33647/2074-5982-18-4-24-38
А . М . Зубалий, М . С . Нестеров, В . Н . Каркищенко, Дмитрий Вадимович Хвостов, Р . А . Агельдинов, С . В . Огнев, A. Zubalii, M. S. Nesterov, V. Karkischenko, D. Khvostov, R. Ageldinov, Sergey V. Ognev
The content of biologically active substances in the gland secretion of Siberian musk deer obtained in vivo was studied by gas chromatography-mass spectrometry using derivatization by silylation. The musk chemical composition of animals held under natural conditions and in captivity was compared. The food spectrum of Siberian musk deer was found to affect the content of biologically active components in the musk, primarily of androsteroid substances. The results of evaluating the content of musk components exhibiting the most pronounced biological effects are presented. An increase in the diversity of food spectrum was established to improve the qualitative composition of biologically active substances in the musk obtained from the adult males of Siberian musk deer held in captivity.
采用硅基衍生化气相色谱-质谱联用技术,研究了在体麝腺体分泌物中生物活性物质的含量。比较了自然饲养和人工饲养动物麝香的化学成分。研究发现,西伯利亚麝的食物谱会影响麝香中生物活性成分的含量,主要是雄性激素物质。介绍了麝香中生物效应最显著的成分含量的测定结果。增加了食物谱的多样性,以改善从圈养的成年雄性西伯利亚麝中获得的麝香中生物活性物质的定性组成。
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引用次数: 0
Analysis of Variations in the Basic Indicators of Mini Pigs under Extreme Physical Exertion 极限运动条件下迷你猪基本指标变化分析
Pub Date : 2022-12-11 DOI: 10.33647/2074-5982-18-4-39-47
N. Stankova, O. V. Alimkina, I. A. Pomytkin, V. Karkischenko
Extreme physical exertion (work to failure) was simulated in untrained mini pigs. The results of complete blood tests, lactate measurements and clinical urine analysis revealed variations in the basic parameters of animals similar to those observed in people after extreme exertion.
在未经训练的迷你猪中模拟极端体力消耗(工作到失败)。完整的血液测试、乳酸测量和临床尿液分析的结果显示,在极端运动后,动物的基本参数发生了与人类相似的变化。
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引用次数: 0
Embryological Aspects of Creating a New Humanized Transgenic Mouse Line with an Integrated Human Gene HLA A*02:01:01:01 构建整合人HLA - a基因的人源化转基因小鼠的胚胎学研究
Pub Date : 2022-12-11 DOI: 10.33647/2074-5982-18-4-10-23
E. S. Savchenko, N. S. Ogneva, N. Karkischenko
The accumulation of scientific data in the field of pharmacogenetics requires the creation of adequate biomodels to reflect the immunogenetic characteristics of different population groups. We have obtained the ancestors of a new humanized transgenic mouse line carrying the human HLA-A*02:01:01:01 gene, which is characteristic of the Russian population. The new biomodels was created using the pronuclei microinjection method of a linearized fragment of genetically engineered DNA construct into zygotes, followed by overnight cultivation in CO2 incubator and transfer of potentially modified embryos at the stage of two 4.0 blastomere to pseudopregnant foster females. A total of 91 living offspring were obtained and analyzed, with 18 pups carrying the target genome modification. The resulting transgenic animals were used to create a new line of mouse biomodels carrying the human HLA-A*02:01:01:01 gene.
药物遗传学领域科学数据的积累需要创建足够的生物模型来反映不同人群的免疫遗传学特征。我们获得了一种新的携带人类HLA-A*02:01:01基因的人源化转基因小鼠系的祖先,这是俄罗斯人群的特征。新的生物模型采用原核微注射方法,将线性化的基因工程DNA片段注入受精卵中,然后在CO2培养箱中过夜培养,并将两个4.0卵裂球阶段的潜在修饰胚胎转移到假怀孕的寄养雌性中。共获得并分析了91只活着的后代,其中18只幼崽携带目标基因组修饰。由此产生的转基因动物被用来创造一种新的携带人类HLA-A*02:01:01基因的小鼠生物模型。
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引用次数: 1
Experimental Evaluation of the Effectiveness and Safety of a New Propandic Acid Derivative Exhibiting Cardiotropic Action 一种新型亲心性丙二酸衍生物的有效性和安全性的实验评价
Pub Date : 2022-10-18 DOI: 10.33647/2074-5982-18-3-109-112
D. Ivkin, A. A. Karpov
An entire cycle of preclinical studies of 4-[(3-ethoxy-3-oxopropanoyl)amino]benzoic acid (etmaben) exhibiting cardiotropic action was carried out. Its potential action mechanism and pharmacological effects, general toxic effects in acute and chronic experiments, specific types of toxicity (allergenicity, immunotoxicity, reproductive toxicity, mutagenicity), and pharmacokinetics were studied. The drug was found to have a pronounced cardiotropic effect and a positive safety profile, which justifies the launch of phase I clinical trials.
4-[(3-乙氧基-3-氧丙基)氨基]苯甲酸(etmaben)具有致心作用的临床前研究进行了一整个周期。研究了其潜在的作用机制和药理作用、急性和慢性实验中的一般毒性作用、特定毒性类型(致敏性、免疫毒性、生殖毒性、致突变性)和药代动力学。该药物被发现具有明显的心性作用和积极的安全性,这证明了开展I期临床试验的理由。
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引用次数: 0
Evaluation of the Effect of Phyto-Adaptogens on the Performance Capability of Outbred Female Mice 植物适应原对远交种雌性小鼠生产性能影响的评价
Pub Date : 2022-10-18 DOI: 10.33647/2074-5982-18-3-99-103
Y. S. Alekseeva, Yu. N. Meshcheryakova, Ya. V. Shmakova, V. Bolotova
The effect of Eleutherococcus senticosus, Rhaponticum carthamoides and Schisandra chinensis extracts in doses of 10, 25, 50 and 75 mg/kg were studied. The actoprotective activity the studied adaptogens was assessed on outbred female mice in a forced swim test with a load of 10% of the animal's body weight. Dry extracts of Eleutherococcus senticosus (50 mg/kg), Rhaponticum carthamoides (10 mg/kg) and Schisandra chinensis (25 mg/kg) were found to exhibit the most pronounced actoprotective activity.
研究了10、25、50和75 mg/kg剂量下刺痛棘球蚴、红花Rhaponticum carthamoides和五味子提取物的作用。研究的适应原对远交系雌性小鼠的活性保护活性进行了评估,并在动物体重10%的负荷下进行了强迫游泳试验。结果表明,刺棘球绦虫(50 mg/kg)、红花Rhaponticum carthamoides (10 mg/kg)和五味子(25 mg/kg)的干提取物具有最显著的活性保护作用。
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引用次数: 0
Effect of Saccharina latissima Extract on the Antioxidant System Parameters of Rat Blood After Exposure to Carbendazim 糖精提取物对多菌灵作用后大鼠血液抗氧化系统参数的影响
Pub Date : 2022-10-18 DOI: 10.33647/2074-5982-18-3-113-117
M. Melnikova, V. Kashuro, E. G. Batotsyrenova, L. G. Kubarskaya, E. A. Zolotoverkhaia, T. A. Kolbasova, O. Vakunenkova, A. Gladchuk
An experimental study of antioxidant parameters in rats after exposure to carbendazim was carried out to study the effect of their pharmacological correction by an intragastric administration of Saccharina latissima extract at a dose of 250 mg/kg for 14 days. The extract under study was found to reduce the activity of lipid peroxidation and promote the neutralization of hydrogen peroxide.
本实验研究了多菌灵对大鼠抗氧化参数的影响,研究了糖精提取物以250 mg/kg剂量灌胃14 d对其药理校正的影响。所研究的提取物可以降低脂质过氧化活性,促进过氧化氢的中和。
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引用次数: 0
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