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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
罗镧1△,印其友2△,施辉3*,陈金霞3,张志军4
0
(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)
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。
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
DOI:10.3724/SP.J.1008.2008.01046
投稿时间:2008-03-05修订日期:2008-06-16
基金项目: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
LUO Lan1△,YIN Qi-you2△,SHI Hui3*,CHEN Jin-xia3,ZHANG Zhi-jun4
(1.Department of Geratology,Affiliated Hospital of Nantong University,Nantong 226001,China*2.Department of Pediatric Surgery,Affiliated Hospital of Nantong University,Nantong 226001*3.Department of Nephrology,Affiliated Hospital of Nantong University,Nantong 226001*4.Department of Anatomy,Medical College of Nantong University,Nantong 226001)
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.
Key words:  diabetic nephropathy  Fas/Fas-L  real-time quantitative polymerase chain reaction  simvastatin