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Hormonal and Metabolic Status of Male Rats with Metabolic Syndrome Model Induced by Interruption of Breastfeeding in the Early Postnatal Period 产后早期中断母乳喂养诱导的代谢综合征模型雄性大鼠的激素和代谢状况
Pub Date : 2022-10-17 DOI: 10.33647/2074-5982-18-3-67-71
A. Shpakov, V. Bondareva, K. Derkach
A short-term deprivation of rat pups from breastfeeding in the early postnatal period leads to MS at the age of 4-6 months. However, this neonatal MS model requires optimization and a detailed study into the metabolic and hormonal parameters of adult animals. The aim of the work was to study these parameters in adult male rats deprived of breast milk at the age of 19-21 days, which was achieved by treating lactating females with bromocriptine. Adult male rats showed an increased body weight and adipose tissue, impaired glucose tolerance, insulin resistance, and hyperleptinemia. These animals had reduced levels of testosterone, free thyroxine, and total triiodothyronine, with an increase in the thyroid-stimulating hormone. Thus, a short-term deprivation of breastfeeding in adult rats leads to the development of MS and endocrine dysregulations.
在产后早期短期剥夺大鼠幼崽的母乳喂养可导致4-6个月大的多发性硬化症。然而,这种新生儿MS模型需要优化和对成年动物代谢和激素参数的详细研究。这项工作的目的是在19-21日龄被剥夺母乳的成年雄性大鼠中研究这些参数,这是通过给哺乳期雌性大鼠服用溴隐亭来实现的。成年雄性大鼠表现出体重和脂肪组织增加,葡萄糖耐量受损,胰岛素抵抗和高瘦素血症。这些动物的睾酮、游离甲状腺素和总三碘甲状腺原氨酸水平降低,而促甲状腺激素水平升高。因此,短期剥夺成年大鼠的母乳喂养会导致MS的发展和内分泌失调。
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引用次数: 0
Dynamics of Changes in Acetylcholinesterase Activity in the Brain and Bood of Rats During Pharmacological Correction of Seizures Caused by Carbamate 氨基甲酸酯致癫痫药物纠正过程中大鼠脑和血乙酰胆碱酯酶活性的动态变化
Pub Date : 2022-10-17 DOI: 10.33647/2074-5982-18-3-27-31
A. S. Melekhova, L. G. Kubarskaya, A. Petrov, A. Bespalov, A. B. Verveda, A. V. Belskaya, M. Melnikova
To simulate a convulsive syndrome, phenylcarbamate was administered intraperitoneally at a dose of 1 mg/kg. Valproic acid aminoester (43 mg/kg), caramiphene (50 mg/kg), and diferidine (2 mg/kg) were investigated as potential anticonvulsant drugs. Blood and brain tissue for the determination of acetylcholinesterase (AСhE) were taken at 10, 30, 60 minutes, 6 and 24 hours after administration of the xenobiotic. In case of poisoning with reversible inhibitors of AChE and accumulation of acetylcholine in the CNS synapses (due to inhibition of AChE activity), only the initial manifestations of convulsive activity are caused, and other mechanisms not associated with AChE inhibition are responsible for the processes of further maintenance and recurrence of seizures.
为了模拟惊厥综合征,苯基氨基甲酸酯以1mg /kg的剂量腹腔注射。研究丙戊酸氨基酯(43 mg/kg)、焦米酚(50 mg/kg)和异苯胺(2 mg/kg)作为潜在的抗惊厥药物。在给药后10、30、60分钟、6和24小时取血和脑组织测定乙酰胆碱酯酶(AСhE)。如果使用可逆的AChE抑制剂和乙酰胆碱在中枢神经系统突触的积累中毒(由于AChE活性的抑制),只引起惊厥活动的初始表现,其他与AChE抑制无关的机制负责癫痫发作的进一步维持和复发过程。
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引用次数: 0
Proinsulin C-peptide Improves metabolic and Hormonal Parameters in Rats with Type 2 Diabetes Mellitus Having Normal but not Elevated Insulin Levels 胰岛素原c肽改善胰岛素水平正常但不升高的2型糖尿病大鼠的代谢和激素参数
Pub Date : 2022-10-17 DOI: 10.33647/2074-5982-18-3-90-94
K. Derkach, V. Bondareva, N. E. Basova, A. Shpakov
In type 2 diabetes mellitus (DM2), the impaired functions of the brain insulin system are associated with the weakened insulin transport through the blood-brain barrier due to insulin resistance. Insulin deficiency in the brain can be corrected by intranasal administration of insulin (II), whose effect may be enhanced by intranasal administration of C-peptide (ICP). In this work, we study the effect of treating hyperinsulinemic and normoinsulinemic DM2 rats with ICP (36 µg/rat/day), II (20 µg/rat/day) and ICP+II on metabolic and hormonal parameters. In normoinsulinemic DM2, ICP attenuated thyroid hormone deficiency and enhanced the restorative effects of II on glucose, insulin, and leptin sensitivity. In hyperinsulinemic DM2, ICP was ineffective, and its combination with II weakened the restorative effects of II. Thus, ICP and its combination with II are effective in restoring metabolic and hormonal parameters in normoinsulinemic, but not hyperinsulinemic, DM2.
在2型糖尿病(DM2)中,脑胰岛素系统的功能受损与胰岛素抵抗导致的胰岛素通过血脑屏障的转运减弱有关。脑内胰岛素缺乏症可以通过鼻内给药胰岛素(II)来纠正,其作用可以通过鼻内给药c肽(ICP)来增强。在这项工作中,我们研究了ICP(36µg/大鼠/天)、II(20µg/大鼠/天)和ICP+II治疗高胰岛素血症和正常胰岛素血症DM2大鼠对代谢和激素参数的影响。在正常胰岛素DM2水平下,ICP可减轻甲状腺激素缺乏,并增强II对葡萄糖、胰岛素和瘦素敏感性的恢复作用。在高胰岛素血症DM2中,ICP无效,与II合用削弱了II的恢复作用。因此,ICP及其联合II对恢复正常胰岛素水平的DM2的代谢和激素参数有效,但对高胰岛素水平的DM2无效。
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引用次数: 0
Antioxidant Effects of Modified-Release Peptide Extracts in Correcting Light Desynchronosis 修饰释放肽提取物在纠正光不同步中的抗氧化作用
Pub Date : 2022-10-17 DOI: 10.33647/2074-5982-18-3-50-57
A. V. Sharabanov, E. G. Batotsyrenova, V. Kashuro, M. T. Gasanov, Yu. V. Komov
This research was aimed at creating novel domestic medical preparations with a modified release of active peptide substances obtained from renewable sources of biological materials. These preparations can be used for the purposes of pharmacological correction of desynchronosis by the action of biologically active substances on the processes of lipid peroxidation and antioxidant protection of cells in order to increase the body's resistance to the negative effects of various stress factors. The conducted studies have confirmed the efficacy of modified-release peptide extracts when correcting the body's oxidative status in various types of desynchronosis.
本研究旨在创造一种新型的国产药物制剂,其活性肽物质的修饰释放来自可再生生物材料。这些制剂可通过生物活性物质对脂质过氧化过程的作用和细胞的抗氧化保护,用于药物纠正不同步的目的,以增加机体对各种应激因素的负面影响的抵抗力。所进行的研究证实了修饰释放肽提取物在纠正各种类型的不同步的身体氧化状态时的功效。
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引用次数: 1
Disorders in the Functional State of the Central Nervous System, Intestinal Peristalsis and Microbiocenosis in Experimental Barbiturate Poisoning 实验性巴比妥酸盐中毒的中枢神经系统功能状态紊乱、肠蠕动和微生物病
Pub Date : 2022-10-17 DOI: 10.33647/2074-5982-18-3-45-49
N. S. Tropskaya, E. Kislyakova, I. G. Vilkova, Yu. V. Gurman, O. S. Kislitsyna, A. V. Zerebtzov, Yelena Borodina, T. V. Chernen'kaya, T. S. Popova
Following a single administration of sodium thiopental in high doses (85 mg/kg intraperitoneally), the animals demonstrated the absence or weakening of reflexes at the levels of the spinal cord, medulla oblongata, bridge and midbrain and cerebral cortex over the period of one day. Other signs included a pronounced hypothermia, a decrease in the respiratory rate and a violation of its rhythm, a distinct tendency to bradycardia. On days 1-3 after the administration of sodium thiopental, a restoration of the respiratory rate, heart rate, body temperature, and the functional state of the central nervous system at various levels was observed, with the exception of the cerebral cortex. In the long term, following the administration of sodium thiopental for up to 21 days, a depression of the functional state of the central nervous system at the level of the cerebral cortex, violation of coordinated propulsive peristalsis of the small intestine and intestinal microbiocenosis were detected. Hence, in experimentally simulated barbiturate poisoning, not only is the suppression of the functions of the central nervous system observed, but also significant and prolonged restructuring of the functional state of the gastrointestinal tract.
在单次高剂量硫喷妥钠(85 mg/kg腹腔注射)后,动物在一天内表现出脊髓、延髓、桥、中脑和大脑皮层水平的反射缺失或减弱。其他症状包括明显的体温过低,呼吸频率降低,节律紊乱,明显的心动过缓倾向。在给予硫喷妥钠后第1-3天,观察到呼吸频率、心率、体温和中枢神经系统各水平功能状态的恢复,但大脑皮层除外。长期服用硫喷妥钠21天后,可观察到大脑皮层水平中枢神经系统功能状态下降,小肠协调推进性蠕动破坏,肠道微生物病。因此,在实验模拟巴比妥酸盐中毒中,不仅观察到中枢神经系统功能的抑制,而且还观察到胃肠道功能状态的显著和长期重构。
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引用次数: 1
Application of an Allosteric Agonist of the Luteinizing Hormone Receptor for Reducing the Effective Dose of Gonadotropin in the Treatment of Androgen Deficiency in Rats with Type 1 Diabetes 黄体生成素受体变构激动剂在降低促性腺激素有效剂量治疗1型糖尿病大鼠雄激素缺乏中的应用
Pub Date : 2022-10-17 DOI: 10.33647/2074-5982-18-3-72-78
A. Bakhtyukov, K. Derkach, V. Sorokoumov, A. Shpakov
In type 1 diabetes mellitus, the impaired testosterone synthesis in the testes leads to androgen deficiency. The long-term application of high gonadotropin doses for its correction decreases the sensitivity of luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptors in Leydig cells to the endogenous gonadotropins. The aim of this work was to study the effect of a 3-day treatment of male Wistar rats with streptozotocin type 1 diabetes with the 5-amino-N-tert-butyl-2-(methylsulfanyl)-4-(3-(nicotinamido) phenyl)thieno[2,3-d]pyrimidine-6-carboxamide allosteric LH/hCG receptor agonist (TP03, 15 mg/kg/day) on steroidogenic effects of a relatively low-dose hCG (10 IU/rat, single dose, s.c.). Pretreatment of diabetic rats with TP03 enhanced the stimulatory effect of hCG on testosterone levels, slightly modifying its effects on the expression of steroidogenic proteins (Star, Cyp11a1, Cyp17a1) and LH/hCG receptor (Lhr) genes. Thus, in type 1 diabetes, TP03 increases the steroidogenic effect of low-dose hCG, at the same time as maintaining its effect on the gene expression of LH/hCG receptor and steroidogenesis enzymes in the testes.
在1型糖尿病中,睾丸激素合成受损导致雄激素缺乏。长期应用高剂量的促性腺激素进行校正会降低间质细胞中促黄体生成素/人绒毛膜促性腺激素(LH/hCG)受体对内源性促性腺激素的敏感性。本研究的目的是研究用5-氨基- n -叔丁基-2-(甲基磺胺基)-4-(3-(烟酰胺)苯基)噻吩[2,3-d]嘧啶-6-羧酰胺变构LH/hCG受体激动剂(TP03, 15 mg/kg/天)治疗链脲霉素1型糖尿病雄性Wistar大鼠3天对相对低剂量hCG (10 IU/大鼠,单剂量,s.c)的甾体致生作用。TP03对糖尿病大鼠的预处理增强了hCG对睾酮水平的刺激作用,轻微改变了其对类固醇蛋白(Star、Cyp11a1、Cyp17a1)和LH/hCG受体(Lhr)基因表达的影响。因此,在1型糖尿病中,TP03在维持其对睾丸LH/hCG受体基因表达和类固醇生成酶的影响的同时,增加了低剂量hCG的类固醇生成作用。
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引用次数: 0
Evaluation of Single-Nucleotide Polymorphisms in Human Serum Albumin Associated with Alzheimer's Disease 与阿尔茨海默病相关的人血清白蛋白单核苷酸多态性的评价
Pub Date : 2022-10-16 DOI: 10.33647/2074-5982-18-3-14-17
E. Deryusheva, E. Litus
Human serum albumin (HSA) is a natural buffer for amyloid в peptide (Аβ), which is a key factor in the development of Alzheimer's disease (AD). An increase in HSA affinity to Аβ can be achieved via HSA saturation with low-molecular-weight ligands, such as serotonin or specific fatty acids. The conducted analysis of the genomic data of exomes (WES) associated with AD (ADSP database) revealed the presence of a single-nucleotide polymorphism of the HSA gene at the binding sites of ibuprofen, arachidonic and oleic acids. Research into the properties of the revealed genetic variants of HSA should be carried out to determine those variants that are susceptible to the modulatory action of HSA ligands, thus increasing its affinity to Aβ.
人血清白蛋白(HSA)是淀粉样蛋白肽(Аβ)的天然缓冲剂,是阿尔茨海默病(AD)发展的关键因素。通过低分子量配体(如5 -羟色胺或特定脂肪酸)饱和HSA,可以增加HSA对Аβ的亲和力。对AD相关外显子组(WES)的基因组数据(ADSP数据库)进行分析发现,HSA基因在布洛芬、花生四烯酸和油酸的结合位点存在单核苷酸多态性。对已发现的HSA遗传变异的性质进行研究,以确定哪些变异易受HSA配体的调节作用,从而增加其对Aβ的亲和力。
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引用次数: 0
The Effect of GABA on the Gut Microbiota During Metabolic Stress 代谢应激时GABA对肠道微生物群的影响
Pub Date : 2022-10-16 DOI: 10.33647/2074-5982-18-3-10-13
Yu. V. Gurman, N. S. Tropskaya, T. V. Chernen'kaya, T. S. Popova
The effect of gamma-aminobutyric acid (GABA) on the gut microbiota was evaluated in experiments on 47 rats with metabolic stress (MS) induced by food deprivation. MS was found to be associated with changes in the qualitative and quantitative composition of the caecum microbiota, including the redistribution of opportunistic flora, the growth of pathogenic microorganisms, as well as a decreased number of lactobacilli and bifidobacteria. Daily administration of GABA at a dose of 70 mg/kg during MS led to a decrease in the number of pathogens, thus leading to the restoration of normal eubionts in the cecum.
采用47只食物剥夺引起代谢应激(MS)的大鼠,研究了γ -氨基丁酸(GABA)对肠道菌群的影响。MS与盲肠菌群的定性和定量组成的变化有关,包括机会菌群的重新分布,致病微生物的生长,以及乳酸菌和双歧杆菌数量的减少。在MS期间,每天给药70 mg/kg的GABA导致病原体数量减少,从而导致盲肠中正常益生菌的恢复。
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引用次数: 0
Preparation of Bacterial Recombinant Myostatin to Induce the Synthesis of Myostatin-Specific Autoantibodies 细菌重组肌生长抑制素的制备诱导合成肌生长抑制素特异性自身抗体
Pub Date : 2022-10-16 DOI: 10.33647/2074-5982-18-3-22-26
E. Koloskova, V. Ezerskiy, O. Zhukova
The myostatin protein, belonging to the family of growth factors, represents a potential target for therapeutic effects in muscular system pathologies. However, this protein is characterized by other beneficial properties. Polymorphisms of the myostatin gene associated with the restriction of its functional activity are useful as genetic markers of meat productivity in farm animals. Blocking the action of myostatin in productive animals can be achieved by inducing the synthesis of specific autoantibodies using recombinant myostatin, possessing sufficient immunogenicity against myostatin as an antigen. A genetic construct was created and an E. coli producer strain with a high level of expression of recombinant myostatin was obtained.
肌生长抑制素蛋白属于生长因子家族,是肌肉系统病变治疗的潜在靶点。然而,这种蛋白质具有其他有益的特性。肌生长抑制素基因的多态性及其功能活性的限制可作为家畜肉品产量的遗传标记。通过利用重组肌生长抑制素诱导合成特异性自身抗体,可以阻断生产动物肌生长抑制素的作用,重组肌生长抑制素作为抗原具有足够的免疫原性。建立了一个基因结构,并获得了一个高水平表达重组肌生长抑制素的大肠杆菌生产菌株。
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引用次数: 1
Changes in the Gut Microbiota of Mice Under the Action of Ultrasonic-induced Stress 超声应激作用下小鼠肠道菌群的变化
Pub Date : 2022-10-16 DOI: 10.33647/2074-5982-18-3-18-21
S. Karabanov, A. Kibitkina
The effect of ultrasound-induced stress on the gut microbiota composition of C57BL/6 mice was studied. Under the action of this type of stress, the gut microbiota composition shifts towards firmicutes at the phylum level. At the family level, an increase in Lachnospiraceae by 67.43%, Rikenellaceae by 39.29%, as well as a decrease in Bacteroidaceae by 64.75% and Prevotellaceae by 38.51%. is observed. The most prominent changes under the action of stress were revealed at the genus level: out of 28 identified genera, significant changes were recorded in 13.
研究超声诱导应激对C57BL/6小鼠肠道菌群组成的影响。在这种应激作用下,肠道菌群组成在门水平上向厚壁菌群转变。在科水平上,毛螺科增加67.43%,里氏菌科增加39.29%,拟杆菌科减少64.75%,普氏菌科减少38.51%。是观察到的。在胁迫作用下,属水平的变化最为显著,28个已鉴定属中有13个发生了显著变化。
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引用次数: 0
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