摘要
目的:观察阿托伐他汀对系膜增殖性肾炎(MsPGN)大鼠肾组织细胞外基质(ECM)和纤溶酶原激活剂抑制物-1(PAI-1)表达的影响,探讨其肾脏保护作用的机制。方法:采用抗胸腺细胞血清诱发的MsPGN大鼠模型,将SD大鼠随机分为正常对照组、肾炎模型组、小剂量阿托伐他汀治疗组(8mg·kg-1·d-1)和大剂量阿托伐他汀治疗组(16mg·kg-1·d-1)。治疗12d后,检测各组大鼠血总胆固醇(CHOL)、甘油三酯(TG)、血肌酐(Scr)和24h尿蛋白,以及肾组织Ⅳ型胶原(ColⅣ)、纤维结合蛋白(FN)和PAI-1的表达。结果:阿托伐他汀治疗组大鼠24h尿蛋白、肾组织ColⅣ、FN和PAI-1 mRNA的表达明显下降,肾组织病理改变明显改善,与模型组相比有统计学差异(P<0.05),且呈剂量依赖关系。其中肾炎模型组尿蛋白(30.34±0.62)mg/d,阿托伐他汀小剂量治疗组(21.17±0.79)mg/d,大剂量治疗组(9.77±0.54)mg/d。同时,各组血脂水平无明显差异(P>0.05)。结论:阿托伐他汀可显著改善MsPGN大鼠肾脏病变,抑制肾组织ECM成分和PAI-1的表达。
Objective： To investigate the reno - protective effects of atorvastatin on experimental mesangial proliferative glomerulonephritis （MsPGN） induced in rats. Methods： MsPGN was induced in Spragne - Dawley rats by intravenous injection of rabbit anti - rat thymocyte serum （ATS）. Rats were randomly divided into normal control group, glomerulonephritis group, lowdose atorvastatin group （8 mg·kg^-1·d^-1） and high-dose atorvastatin group （16 mg·kg^-1·d^-1）. After 12 days of therapy, total cholesterol （CHOL）, triglycerides （TG） and creatinine （Scr） in serum,24 hours urinary protein excretion,collagen Ⅳ （Col Ⅳ ）, fibronectin （FN） and plasminogen activator inhibitor- 1 （PAl - 1 ） were determined. Results： Atorvastatin reduced 24 hours urinary protein excretion and inhibited the expression of Col Ⅳ, FN and PAl - 1 mRNA in a dose- depend manner （P〈0.05,respectively） ,which was associated with significant improvement in pathological changes. Urinary protein excretion rate was respectively （30.34±0.62） mg/d （glomerulonephritis group ）, （21.17 ± 0.79） mg/d （ low - dose atorvastatin group） and （9.77 ±0.54 ） mg/d （high- dose atorvastatin group）. While no significant change in serum total CHOL and TG was found. Conclusion： Atorvastatin improves pathological changes in MsPGN, remarkably suppresses extracellular matrix accumulation and down - regulates the expression of Col Ⅳ, FN and PAl - 1. These amelioration is independent of the lipid - lowering effect by atorvastatin.
出处
《中国中西医结合肾病杂志》
2007年第9期507-510,F0002,共5页
Chinese Journal of Integrated Traditional and Western Nephrology
基金
福建省教育厅科研基金资助项目(No.JA03102)
关键词
系膜增殖性肾炎
阿托伐他汀
细胞外基质
纤溶酶原激活剂抑制物-1
Mesangial proliferative glomemlnephritis（MsPGN） Atorvastatin ExtraceLlular matrix（ECM） Plaminogen activator inhibitor-1（PAI- 1）
