本文選題：糖尿病心肌病變 + PTEN　； 參考：《石河子大學(xué)》2014年碩士論文

【摘要】：目的：通過檢測(cè)螺內(nèi)酯對(duì)2型糖尿病大鼠心肌組織第10號(hào)染色體缺失的磷酸酶和張力蛋白同源基因（PTEN）mRNA、蛋白表達(dá)水平的影響，進(jìn)一步探討非選擇性醛固酮受體拮抗劑螺內(nèi)酯治療糖尿病心肌病變的作用及機(jī)制。 方法：80只健康雄性SD大鼠隨機(jī)分為2組，正常對(duì)照組（NC組，n=12）給予普通飼料喂養(yǎng)；糖尿病模型組（n=68）給予高脂高糖飼料喂養(yǎng)8周后，一次性腹腔注射鏈脲佐菌素（STZ）30mg/kg破壞部分胰島β細(xì)胞，建立2型糖尿病大鼠模型。一周后測(cè)血糖，，造模成功的糖尿病大鼠隨機(jī)分為兩組，糖尿病對(duì)照組（DM組，n=11）和糖尿病螺內(nèi)酯干預(yù)組（DS組，n=12），DS組給予螺內(nèi)酯40mg/（kg d）灌胃，NC組和DM組分別灌胃等量蒸餾水。DM組和DS組繼續(xù)高脂高糖飼料喂養(yǎng)。每?jī)芍鼙O(jiān)測(cè)體重、末梢血糖。螺內(nèi)酯干預(yù)8周后實(shí)驗(yàn)結(jié)束，空腹麻醉采血檢測(cè)總膽固醇（TC）、甘油三酯（TG）、空腹血糖（FBG）、糖化血紅蛋白（GHbA1c）、血鉀（K+）。石蠟包埋及液氮凍存心肌組織，采用免疫組織化學(xué)染色檢測(cè)心肌組織PTEN、p-Akt（Ser473）蛋白的表達(dá)，采用RT-qPCR檢測(cè)心肌組織PTEN mRNA的表達(dá)。 結(jié)果：DM組和DS組TC、TG、FBG、GHbA1c水平均高于NC組（P＜0.01），而在兩組間差異無統(tǒng)計(jì)學(xué)意義，三組之間血鉀水平差異無統(tǒng)計(jì)學(xué)意義（P＞0.05）；DM組大鼠出現(xiàn)心肌肥大而DS組心肌病變明顯減輕；DM組PTEN mRNA和蛋白的表達(dá)明顯低于NC組（P＜0.01），DS組則高于DM組（P＜0.05）；DM組p-Akt（Ser473）蛋白表達(dá)明顯高于NC組（P＜0.01），DS組則低于DM組（P＜0.05）。 結(jié)論：螺內(nèi)酯能通過上調(diào)心肌組織PTEN表達(dá)，抑制Akt磷酸化，減輕2型糖尿病大鼠心肌病變。
[Abstract]:Objective: to investigate the effect of spironolactone on the expression of phosphatase and tension protein homologous gene (PTEN) mRNAs in myocardium of type 2 diabetic rats. To investigate the effect and mechanism of nonselective aldosterone receptor antagonist spironolactone on diabetic cardiomyopathy. Methods 80 healthy male Sprague-Dawley rats were randomly divided into two groups: the normal control group (NC group) was fed with normal diet, the diabetic model group (NN68) was fed with high-fat and high-sugar diet for 8 weeks, and the diabetic model group (NN68) was fed with high fat and high sugar diet for 8 weeks. Streptozotocin (STZ) 30mg/kg was injected intraperitoneally to destroy some islet 尾 cells and to establish type 2 diabetic rat model. One week later, the diabetic rats were randomly divided into two groups. The diabetic control group (DM group) and the diabetic spironolactone intervention group (DS group) were treated with spironolactone 40mg/ (kg d) intragastric perfusion. The NC group and the DM group were fed with the same amount of distilled water. DM group and DS group were fed with high fat and high sugar diet respectively. Body weight and peripheral blood sugar were monitored every two weeks. Total cholesterol (TC), triglyceride (TG), fasting blood glucose (FBG), glycosylated hemoglobin (GHbA1c) and serum potassium (K) were measured after 8 weeks of intervention with spironolactone. The expression of PTEN p-Akt (Ser473) protein in myocardial tissue was detected by immunohistochemical staining, and the expression of PTEN mRNA in myocardial tissue was detected by RT-qPCR. Results compared with NC group, the levels of TCG-FBGnGHbA1c in the two groups were higher than those in the control group (P < 0.01), but there was no significant difference between the two groups. There was no significant difference in serum potassium level between the three groups (P > 0.05). The myocardial hypertrophy was found in the DM group and the cardiomyopathy in the DS group was alleviated. The expression of PTEN mRNA and protein in DM group was significantly lower than that in NC group (P < 0. 01). The expression of p-Akt (Ser473) protein in DM group was significantly higher than that in NC group (P < 0. 01), and the expression of p-Akt (Ser473) protein in DS group was lower than that in DM group (P < 0. 05). Conclusion: spironolactone can inhibit Akt phosphorylation by upregulating the expression of PTEN in myocardium and attenuate cardiomyopathy in type 2 diabetic rats.
【學(xué)位授予單位】：石河子大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R587.2

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