贵州医科大学学报

2008, No.133(04) 380-384

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辛伐他汀对糖尿病大鼠肾脏活化蛋白-1表达的影响
Effects of Simvastatin on Expression of Activator Protein-1 in Renal Tissues of Diabetic Rats

曾家顺;李龙;莫英曼;
ZENG Jiashun,LI Long,MO Yingman (Department of Nephrology,The Affiliated Hospital of Guiyang Medical College,Guiyang 550004,Guizhou,China)

摘要(Abstract):

目的:研究活化蛋白-1(AP-1)在糖尿病大鼠肾脏中的分子机制,探讨辛伐他汀对AP-1的影响及机制。方法:大鼠随机分成正常对照组(C组)、糖尿病组(DM组)和辛伐他汀治疗组(DS组),用原位杂交方法检测各组肾组织AP-1(c-jun mRNA)的表达,免疫组织化学法检测各组肾组织巨噬细胞炎症蛋白-1α(MIP-1α)及纤维连接蛋白(FN)的表达,生化法测定各组血糖、总胆固醇、甘油三酯、肌酐及24 h尿蛋白。结果:DM组AP-1的活性和MIP-1α的表达明显高于C组(P<0.01),DS组AP-1活性降低、MIP-1α和FN低表达(P<0.01)、24 h尿蛋白排泄减少(P<0.01)、改善肾功能指标及肾组织病理学损害。结论:AP-1在糖尿病肾病发生发展中具有重要作用,辛伐他汀抑制AP-1活性可能是其非降脂性肾脏保护的机制之一。
Objective: To study the molecular mechanism of activator protein-1(AP-1) in renal tissues of diabetic rats,and to investigate the effects of simvastatin on AP-1 and its protection to kidney during the development of diabetic nephropathy(DN).Methods: SD male rats were randomly divided into three groups: normal control group(C),diabetic group(DM),and simvastatin treated group(DS).The expression of AP-1(c-jun mRNA)in renal tissues was measured with in situ hybridization.The expressions of macrophage inflammatory protein-1α(MIP-1α) and fibronectin(FN) were measured with Immuno-histochemstry method.The levels of triglyceride(TG),total cholesterol(TC),creatinine(Cr) and 24-hour urine protein excretion were measured with biochemistry methods.Results: The expressions of AP-1,MIP-1α and FN in glomeruli were increased in group DM and were inhibited by simvastatin treatment(P<0.01).The levels of 24-hour urine protein,TG,TC and Cr in group DS were lower than those in group DM(P<0.01).The renal histology changes were markedly relieved in group DS as compared with that in group DM.Conclusions: AP-1 plays an important role in the development of diabetic nephropathy.One of Reno-protective effects of simvastatin might be inhibition of AP-1 activity.

关键词(KeyWords): 糖尿病肾病;活化蛋白-1;巨噬细胞炎性蛋白质;西司他汀类
diabetic nephropathies;activato protein-1;macrophage inflammatory protein-1;cystatins

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作者(Author): 曾家顺;李龙;莫英曼;
ZENG Jiashun,LI Long,MO Yingman (Department of Nephrology,The Affiliated Hospital of Guiyang Medical College,Guiyang 550004,Guizhou,China)

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DOI: 10.19367/j.cnki.1000-2707.2008.04.017

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