【摘要】：DCM是糖尿病的主要慢性并發(fā)癥之一，與糖尿病患者高發(fā)病率和死亡率密切相關(guān)。大量的研究結(jié)果表明，高血糖引起的氧化應(yīng)激在DCM的眾多發(fā)病機(jī)制中起重要作用，是DCM發(fā)生、發(fā)展的重要因素。而氧化應(yīng)激通過調(diào)控細(xì)胞凋亡，促進(jìn)心肌、血管損傷。目前人們對人參皂苷Re發(fā)揮心肌保護(hù)作用的認(rèn)識，主要集中在抗缺血性心肌病的動物模型中，而對于糖尿病患者心肌是否也具有保護(hù)作用，目前還未見報(bào)道。本實(shí)驗(yàn)主要從人參皂苷Re對糖尿病大鼠心肌組織的抗氧化和抗細(xì)胞凋亡的作用入手，研究人參皂苷Re對糖尿病心肌病的心肌的保護(hù)作用。 實(shí)驗(yàn)選用健康雄性Wistar大鼠50只，體重（160±20）g，隨機(jī)分為四組，空白組（C組）10只，其余40只大鼠腹腔注射鏈脲佐菌素（STZ）35mg/kg制造糖尿病大鼠模型，以72h后隨機(jī)血糖≥16.7mmol/L為造模成功，造模成功后將大鼠隨機(jī)分為糖尿病模型組（DM組），人參皂苷Re組（Re組），吡格列酮組（P組），分別給予相應(yīng)量的純凈水，人參皂苷Re25mg/（kg d），吡格列酮10mg/（kg d）灌胃，連續(xù)給藥4周。4周后處死大鼠，分別檢測血糖、血脂，血清和心肌組織中SOD活性和MDA含量以及心肌組織中Bcl-xl，caspase9表達(dá)，觀察心肌結(jié)構(gòu)改變。 結(jié)果表明，Re組和P組均能夠明顯改善糖尿病大鼠多食、多飲、多尿癥狀，增加體重，改善大鼠生存質(zhì)量，Re組和P組比較無統(tǒng)計(jì)學(xué)差異（P＞0.05）。與DM組比較，Re組和P組均能降低空腹血糖和血清總膽固醇，差異有統(tǒng)計(jì)學(xué)意義（P0.01），但兩組空腹血糖和血清總膽固醇水平較C組高（P0.01），Re組和P組之間無統(tǒng)計(jì)學(xué)差異（P＞0.05）。與DM組比較，Re組和P組均能提高血清和心肌組織中SOD活性，降低MDA含量，差異有統(tǒng)計(jì)學(xué)意義（P0.01或P0.05），兩組SOD活性較C組低，MDA含量較C組高（P0.05），但Re組和P組之間無統(tǒng)計(jì)學(xué)差異（P＞0.05）。心肌組織病理學(xué)觀察顯示：與DM組比較，Re組和P組都能夠減輕心肌組織損傷程度，降低心肌膠原纖維及毛細(xì)血管周圍膠原纖維含量，減少心肌細(xì)胞間質(zhì)炎細(xì)胞浸潤和心肌壞死程度；心肌凋亡相關(guān)蛋白表達(dá)結(jié)果顯示，與DM組比較，Re組和P組均能明顯減少凋亡蛋白caspase-9的表達(dá)，提高抗凋亡蛋白Bcl-xl的表達(dá)，差異有統(tǒng)計(jì)學(xué)意義（P0.01），但Re組和P組之間無統(tǒng)計(jì)學(xué)差異（P＞0.05）。 人參皂苷Re能降低空腹血糖和血清總膽固醇；能顯著提高血清和心肌組織中SOD活性，降低MDA含量；能改善心肌組織結(jié)構(gòu)的損傷，減少心肌膠原纖維及毛細(xì)血管周圍膠原纖維含量；能抑制caspase-9蛋白，提高Bcl-xl蛋白的表達(dá)，抑制心肌細(xì)胞凋亡，，提高心肌細(xì)胞存活率，發(fā)揮心肌保護(hù)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 鹵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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R-332

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