人参皂苷Re对糖尿病早期抗氧化和抗细胞凋亡作用的研究

发布时间：2018-11-08 12:43

【摘要】：DCM是糖尿病的主要慢性并发症之一，与糖尿病患者高发病率和死亡率密切相关。大量的研究结果表明，高血糖引起的氧化应激在DCM的众多发病机制中起重要作用，是DCM发生、发展的重要因素。而氧化应激通过调控细胞凋亡，促进心肌、血管损伤。目前人们对人参皂苷Re发挥心肌保护作用的认识，主要集中在抗缺血性心肌病的动物模型中，而对于糖尿病患者心肌是否也具有保护作用，目前还未见报道。本实验主要从人参皂苷Re对糖尿病大鼠心肌组织的抗氧化和抗细胞凋亡的作用入手，研究人参皂苷Re对糖尿病心肌病的心肌的保护作用。实验选用健康雄性Wistar大鼠50只，体重（160±20）g，随机分为四组，空白组（C组）10只，其余40只大鼠腹腔注射链脲佐菌素（STZ）35mg/kg制造糖尿病大鼠模型，以72h后随机血糖≥16.7mmol/L为造模成功，造模成功后将大鼠随机分为糖尿病模型组（DM组），人参皂苷Re组（Re组），吡格列酮组（P组），分别给予相应量的纯净水，人参皂苷Re25mg/（kg d），吡格列酮10mg/（kg d）灌胃，连续给药4周。4周后处死大鼠，分别检测血糖、血脂，血清和心肌组织中SOD活性和MDA含量以及心肌组织中Bcl-xl，caspase9表达，观察心肌结构改变。结果表明，Re组和P组均能够明显改善糖尿病大鼠多食、多饮、多尿症状，增加体重，改善大鼠生存质量，Re组和P组比较无统计学差异（P＞0.05）。与DM组比较，Re组和P组均能降低空腹血糖和血清总胆固醇，差异有统计学意义（P0.01），但两组空腹血糖和血清总胆固醇水平较C组高（P0.01），Re组和P组之间无统计学差异（P＞0.05）。与DM组比较，Re组和P组均能提高血清和心肌组织中SOD活性，降低MDA含量，差异有统计学意义（P0.01或P0.05），两组SOD活性较C组低，MDA含量较C组高（P0.05），但Re组和P组之间无统计学差异（P＞0.05）。心肌组织病理学观察显示：与DM组比较，Re组和P组都能够减轻心肌组织损伤程度，降低心肌胶原纤维及毛细血管周围胶原纤维含量，减少心肌细胞间质炎细胞浸润和心肌坏死程度；心肌凋亡相关蛋白表达结果显示，与DM组比较，Re组和P组均能明显减少凋亡蛋白caspase-9的表达，提高抗凋亡蛋白Bcl-xl的表达，差异有统计学意义（P0.01），但Re组和P组之间无统计学差异（P＞0.05）。人参皂苷Re能降低空腹血糖和血清总胆固醇；能显著提高血清和心肌组织中SOD活性，降低MDA含量；能改善心肌组织结构的损伤，减少心肌胶原纤维及毛细血管周围胶原纤维含量；能抑制caspase-9蛋白，提高Bcl-xl蛋白的表达，抑制心肌细胞凋亡，，提高心肌细胞存活率，发挥心肌保护作用。
[Abstract]:DCM is one of the main chronic complications of diabetes, which is closely related to the high morbidity and mortality of diabetes. A large number of studies have shown that oxidative stress induced by hyperglycemia plays an important role in the pathogenesis of DCM and is an important factor in the occurrence and development of DCM. Oxidative stress promotes myocardial and vascular injury by regulating cell apoptosis. At present, the recognition that ginsenoside Re plays a role in myocardial protection is mainly concentrated in the animal model of anti-ischemic cardiomyopathy, but it has not been reported that it can also protect the myocardium of diabetic patients. In this study, the protective effect of ginsenoside Re on diabetic cardiomyopathy was studied by studying the effects of ginsenoside Re on anti-oxidation and anti-apoptosis of myocardial tissue of diabetic rats. Fifty healthy male Wistar rats with body weight of (160 卤20) g were randomly divided into four groups: group C (n = 10) and group C (n = 10). The other 40 rats were injected intraperitoneally with streptozotocin (STZ) 35mg/kg) to produce diabetic rats. The rats were randomly divided into diabetic model group (DM group), ginsenoside Re group (Re group) and pioglitazone group (P group). Ginsenoside Re25mg/ (kg d), pioglitazone 10mg/ (kg d) was administered intragastrically for 4 weeks. Rats were killed after 4 weeks of administration. Blood glucose, blood lipid, SOD activity and MDA content in serum and myocardial tissue, and Bcl-xl, in myocardial tissue were detected respectively. The expression of caspase9 and the changes of myocardial structure were observed. The results showed that Re group and P group could significantly improve the symptoms of polydiet, polydrink, polyuria, increase body weight and improve the quality of life in diabetic rats. There was no significant difference between Re group and P group (P > 0. 05). Compared with DM group, Re group and P group could decrease fasting blood glucose and serum total cholesterol significantly (P0.01), but the fasting blood glucose and serum total cholesterol level of two groups were higher than that of C group (P0.01). There was no significant difference between Re group and P group (P > 0. 05). Compared with DM group, Re group and P group could increase SOD activity and decrease MDA content in serum and myocardium (P0.01 or P0.05). SOD activity in two groups was lower than that in C group, and MDA content was higher than that in C group (P0.05). But there was no significant difference between Re group and P group (P > 0. 05). Compared with DM group, Re group and P group could reduce the degree of myocardial injury and decrease the content of myocardial collagen fiber and pericapillary collagen fiber. Reduce the degree of myocardial interstitial inflammation cell infiltration and myocardial necrosis; The results of myocardial apoptosis-related protein expression showed that both Re and P groups could significantly decrease the expression of apoptotic protein caspase-9 and increase the expression of anti-apoptotic protein Bcl-xl compared with DM group (P0.01). But there was no significant difference between Re group and P group (P > 0. 05). Ginsenoside Re could decrease fasting blood glucose and serum total cholesterol, increase the activity of SOD in serum and myocardium, and decrease the content of MDA. It can improve the injury of myocardial tissue structure and reduce the content of myocardial collagen fiber and collagen fiber around capillaries. It can inhibit the expression of caspase-9 protein, increase the expression of Bcl-xl protein, inhibit cardiomyocyte apoptosis, improve the survival rate of cardiomyocytes, and play a role in myocardial protection.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R-332

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