摘要
目的:探讨羟甲基戊二酰辅酶A还原酶抑制剂(HCRI)氟伐他汀对肾小球硬化大鼠Ⅳ型胶原的影响。方法:用5/6肾切除的方法诱导大鼠肾小球硬化模型,随机分为对照组、氟伐他汀治疗组2mg/(kg·d)、苯那普利治疗组6mg/(kg·d)及假手术组。10周时测尿量、尿蛋白、内生肌酐清除率(Ccr)、血肌酐、血胆固醇和血甘油三酯。免疫组化检测肾组织Ⅳ型胶原水平表达。蛋白印迹(Westernblotting)测定肾皮质纤维蛋白溶解酶原激活物抑制剂-1(PAI-1)蛋白水平表达。结果:氟伐他汀及苯那普利治疗组尿蛋白及肾组织Ⅳ型胶原水平表达明显低于对照组(P<0.01),PAI-1表达亦低于对照组,Ccr明显高于对照组(P<0.01)。结论:氟伐他汀可抑制PAI-1,减少Ⅳ型胶原积聚,减轻肾小球硬化,降低蛋白尿,改善肾功能,其对肾脏的保护作用并不依赖降胆固醇作用。
Objective:To investigate the effect of hydroxyl methylglulary coenzyme A reductase inhibitor (HCRI) fluvastatin on plasminogen activator inhibitor 1 (PAI 1) and collagen type Ⅳin rats of glomerular sclerosis. Methods:Five sixths nephrectomized rats were randomly divided into 4 groups: control group; treated with fluvastatin group 2 mg/(kg·d); treated with benazepril group 6 mg/(kg·d)and pesudonephreotomized group. Urinary Volume, proteinuria, creatinine clearance rate (Ccr),serum creatinine, cholesterol and triglyceride were reviewed after 10 weeks of treatment, while the expression of PAI 1 and collagen type Ⅳprotein were measured by the methods of western blot and immunohistological staining respectively. Results:Proteinuria and the expression of PAI 1?collagen type Ⅳin rats of fluvastatin and benazepril groups were significantly lower than the control (P< 0.01). Compared to control group, there was a significant increase in Ccr in groups treated with fluvastatin and benazepril (P< 0.01). Conclusion:Fluvastatin not only reduces proteinuria, improves renal function, but also modulates glomerular sclerosis by inhibiting activity of PAI 1 and decreasing accumulation of collagen type Ⅳ. The mechanism of renal protective effect is independent of a reduction of circulating cholesterol.
出处
《南京医科大学学报（自然科学版）》
CAS
CSCD
北大核心
2002年第6期486-488,491,F003,共5页
Journal of Nanjing Medical University(Natural Sciences)
基金
江苏省教育厅自然科学基金资助项目(OOKJD320011)
关键词
氟伐他汀
肾小球硬化
大鼠
纤维蛋白溶解酶原激活物抑制剂-1
Ⅳ型胶原
hydroxyl methylglulary coenzyme A reductase inhibitor
fluvastatin
glomerular sclerosis
collage typeⅣ
plasminogen activator inhibitor 1
