辛伐他汀对单肾切除糖尿病老龄鼠肾组织Fas/Fas-L基因表达的影响
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江苏省高校自然科学基金 (05KJD350164),南通大学自然科学基金(05Z094)


Effects of simvastatin on renal expression of Fas/Fas-L in aged diabetic rats after uninephrectomy
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Supported by Natural Science Fundation of Jiangsu Province(05KJD350164) and Nantong University(05Z094).

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    摘要:

    目的:探讨辛伐他汀对单肾切除糖尿病老龄SD大鼠肾脏凋亡相关基因Fas/Fas-L表达的影响。方法:单肾切除老龄SD大鼠分为肾切除对照组(C组)、糖尿病模型组(D组)、糖尿病辛伐他汀治疗组(S组)。12周后采用原位末端标记法检测各组肾组织细胞凋亡指数,使用实时荧光定量PCR和免疫荧光法,从转录和翻译水平观察各组大鼠肾皮质中凋亡相关基因Fas及Fas-L的变化规律。结果:D组相对C组细胞凋亡指数、Fas及Fas-L的蛋白表达水平和相对应的mRNA拷贝数均明显增高,S组相对D组减弱(P<0.05),Fas、Fas-L蛋白主要在肾小管表达。结论:Fas及Fas-L系统与DN发生发展相关,辛伐他汀可在分子水平调控Fas及Fas-L基因的转录和翻译,抑制细胞凋亡,发挥肾脏保护作用。

    Abstract:

    Objective:To explore the effects of hydroxy-methyl-glutaryl coenzymeA reductase inhibitor (HMG-CoA RI) simvastatin on renal expression of apoptosis related gene Fas/Fas-L in aged diabetic rats after uninephrectomy.Methods: Elderly uninephrectomized SD rats were randomly divided into uninephrectomized control group (group C),streptozocin(STZ)-induced diabetic model group( group D),and diabetes + simvastatin group (group S).The apoptosis indices in renal tisses of three groups were detected by terminal deoxynucleotide mediated nick end labeling 12 weeks later.Immunofluorescence and real-time quantitative PCR were employed to observe the expression changes of Fas/Fas-L genes at the transcription and translation levels.Results: Compared with group C,group D had significantly higher apoptosis index and expression level of Fas/Fas-L; the above parameters were lower in group S compared with those in group D (P<0.05).The expression of Fas/Fas-L protein was mainly in the renal tubules.Conclusion:Both Fas and Fas-L genes are associated with the development and progression of diabetic nephropathy in aged rats.Simvastatin can down-regulate the translation and transcription of the genes,inhibit cell apoptosis and protect the kidney.

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  • 收稿日期:2008-03-05
  • 最后修改日期:2008-06-16
  • 录用日期:2008-06-16
  • 在线发布日期: 2008-09-12
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