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  

Effects of simvastatin on renal expression of Fas/Fas-L in aged diabetic rats after uninephrectomy

作　　者：罗镧[1] 印其友[2] 施辉[3] 陈金霞[3] 张志军[4] 

机构地区：[1]南通大学附属医院老年医学科,南通226001 [2]南通大学附属医院小儿外科,南通226001 [3]南通大学附属医院肾脏内科,南通226001 [4]南通大学医学院人体解剖教研室,南通226001

出　　处：《第二军医大学学报》2008年第9期1046-1051,共6页Academic Journal of Second Military Medical University

基　　金：江苏省高校自然科学基金(05KJD350164);南通大学自然科学基金(05Z094);Natural Science Fundation of Jiangsu Province(05KJD350164);Nantong University(05Z094)

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。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）-indueed 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.

关 键 词：糖尿病肾病 Fas/Fas—L 实时荧光定量聚合酶链反应 辛伐他汀 

分 类 号：R587.24[医药卫生—内分泌]