螺内酯对2型糖尿病大鼠心肌PTEN表达的影响

发布时间：2018-06-24 02:13

本文选题：糖尿病心肌病变 + PTEN　；参考：《石河子大学》2014年硕士论文

【摘要】：目的：通过检测螺内酯对2型糖尿病大鼠心肌组织第10号染色体缺失的磷酸酶和张力蛋白同源基因（PTEN）mRNA、蛋白表达水平的影响，进一步探讨非选择性醛固酮受体拮抗剂螺内酯治疗糖尿病心肌病变的作用及机制。方法：80只健康雄性SD大鼠随机分为2组，正常对照组（NC组，n=12）给予普通饲料喂养；糖尿病模型组（n=68）给予高脂高糖饲料喂养8周后，一次性腹腔注射链脲佐菌素（STZ）30mg/kg破坏部分胰岛β细胞，建立2型糖尿病大鼠模型。一周后测血糖，，造模成功的糖尿病大鼠随机分为两组，糖尿病对照组（DM组，n=11）和糖尿病螺内酯干预组（DS组，n=12），DS组给予螺内酯40mg/（kg d）灌胃，NC组和DM组分别灌胃等量蒸馏水。DM组和DS组继续高脂高糖饲料喂养。每两周监测体重、末梢血糖。螺内酯干预8周后实验结束，空腹麻醉采血检测总胆固醇（TC）、甘油三酯（TG）、空腹血糖（FBG）、糖化血红蛋白（GHbA1c）、血钾（K+）。石蜡包埋及液氮冻存心肌组织，采用免疫组织化学染色检测心肌组织PTEN、p-Akt（Ser473）蛋白的表达，采用RT-qPCR检测心肌组织PTEN mRNA的表达。结果：DM组和DS组TC、TG、FBG、GHbA1c水平均高于NC组（P＜0.01），而在两组间差异无统计学意义，三组之间血钾水平差异无统计学意义（P＞0.05）；DM组大鼠出现心肌肥大而DS组心肌病变明显减轻；DM组PTEN mRNA和蛋白的表达明显低于NC组（P＜0.01），DS组则高于DM组（P＜0.05）；DM组p-Akt（Ser473）蛋白表达明显高于NC组（P＜0.01），DS组则低于DM组（P＜0.05）。结论：螺内酯能通过上调心肌组织PTEN表达，抑制Akt磷酸化，减轻2型糖尿病大鼠心肌病变。
[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.
【学位授予单位】：石河子大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R587.2

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