氯沙坦和辛伐他汀对糖尿病大鼠BAX/BCL-2 mRNA的影响
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江苏省高校自然科学基金(05KJD350164)资助


Effects of losartan and simvastatin on BAX/BCL-2 mRNA in diabetic rats
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    摘要:

    目的:探讨氯沙坦和辛伐他汀对单肾切除糖尿病大鼠肾脏凋亡相关基因BAX/BCL-2 mRNA的影响。方法:单肾切除SD大鼠分为对照组(C组)、糖尿病模型组(D组)、辛伐他汀治疗组(S组)、氯沙坦治疗组(L组)。采用实时荧光定量PCR法检测各组大鼠治疗2、10周肾皮质中BAX/BCL-2的mRNA表达。结果: 比较各组BAX/BCL-2比值,2周S组明显高于其他组,10周D组明显高于其他组,D组10周较2周明显升高,S组10周较2周明显降低。结论:BAX/BCL-2在糖尿病肾病发生发展中起一定的作用。氯沙坦可能部分通过降低BAX/BCL-2比值,抑制糖尿病肾病晚期细胞凋亡,发挥肾脏保护作用。辛伐他汀对BAX/BCL-2比值有双相调节作用,早期可升高,晚期可降低。

    Abstract:

    Objective: To explore the effects of angiotensin Ⅱ type 1 receptor antagonist(AT1RA) losartan and hydroxy-methyl-glutaryl coenzymeA reductase inhibitor(HMG-CoA RI) simvastatin on transcription of BAX and BCL-2 genes of uninephrectomized diabetic rats. Methods:Uninephrectomized SD rats were randomly divided into control group(group C) and diabetic groups induced by STZ. The diabetic rats were randomly divided into three groups: group D treated with placebo, group L treated with losartan, group S treated with simvastatin. At the same time group C was treated with placebo. At the end of 2 weeks and 10 weeks, the expressions of BAX and BCL-2 were detected by real-time quantitative PCR. Results:After 2 weeks of treatment the ratio of BAX to BCL-2 mRNA in group S increased significantly as compared with group C, group D and group L(P < 0.01). After 10 weeks of treatment the ratio of BAX to BCL-2 mRNA in group D was the highest among four groups(P < 0.01). The ratio of BAX to BCL-2 in group D was significantly increased after 10 weeks compared with 2 weeks(P < 0.01). At the same time the ratio of BAX to BCL-2 mRNA in group S was significantly reduced after 10 weeks, compared with 2 weeks(P < 0.01). Conclusion: Both BCL-2 and BAX play a role in the occurrence and progression of diabetic nephropathy. Losartan might inhibit the apoptosis of kidney through decreasing the ratio of BAX to BCL-2. Simvastatin could increase the ratio of BAX to BCL-2 at the early stage and decrease it at the advanced stage.

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罗 镧,施 辉,印其友.氯沙坦和辛伐他汀对糖尿病大鼠BAX/BCL-2 mRNA的影响[J].南京医科大学学报(自然科学版),2006,(12):1173-1178

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  • 收稿日期:2006-07-28
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