氟伐他汀对5/6肾切除大鼠肾脏皮质细胞外基质积聚的影响  

Effect of fluvastatin on the accumulation of cellular matrix in renal cortex of 5/6 nephrectomized rats

作　　者：宋国炜[1] 李才[1] 于晓艳[1] 苗春生[1] 

机构地区：[1]吉林大学再生医学科学研究所,长春130021

出　　处：《中华肾脏病杂志》2004年第3期203-205,共3页Chinese Journal of Nephrology

基　　金：国家自然科学基金资助项目(39870312)

摘　　要：目的观察降脂药氟伐他汀对5/6肾切除大鼠肾皮质细胞外基质(ECM)积聚的影响和探讨其降脂作用外的肾脏保护机制。方法将5/6肾切除大鼠随机分为模型组和氟伐他汀治疗组(治疗组),另设假手术组作为对照。实验期间测定尿蛋白排泄率;氟伐他汀处理(7mg·kg-1·d-1)13周后免疫组化法检测肾小球Ⅳ型胶原(ColⅣ)及纤连蛋白(FN)蛋白表达;酶谱法检测肾皮质基质金属蛋白酶(MMP)-2活性;免疫印迹检测金属蛋白酶组织抑制物(TIMP)-2蛋白表达。结果与假手术组相比,模型组大鼠尿蛋白排泄、肾小球Ⅳ型胶原和FN表达均明显增加(均为P<0.01)。模型组大鼠肾皮质MMP-2活性较假手术组明显降低(P<0.01),而TIMP-2蛋白表达明显上调(P<0.01)。氟伐他汀治疗后这些改变均明显好转。结论氟伐他汀可能通过增加5/6肾切除大鼠肾脏MMP-2活性和降低TIMP-2表达,从而能增加细胞外基质降解和减轻肾小球细胞外基质积聚。Objective To observe the effect of fluvastatin on the accumutation of cellular matrix in renal cortex of 5/6 nephrectomized (NX) rats and explore its renoprotective mechanism irrelevant to lipid decrease.Methods 5/6 NX rats were randomly divided into 5/6 NX group (model group) and fluvastatin treated 5/6 NX group (treatment group), and sham operation rats served as control(sham operation group). Urinary protein excretion was determined in the experimental period. After fluvastatin was orally administered(7 mg·kg-1·d-1)for 13 weeks,immunohistochemstry was used to examine type Ⅳcollagen and fibronectin(FN) protein expression in glomeruli.MMP 2 activity and TIMP 2 protein expression in renal cortex were assessed by zymography and Western blot respectively.Results Urinary protein excretion as well as the expression of type Ⅳcollagen and fibronectin proteins in glomeruli of model group increased significantly as compared with sham operation group(all P< 0.01). MMP 2 activity in renal cortex of model group was lower than that of sham operation group(P< 0 01),while TIMP 2 protein expression was markedly upregulated(P< 0 01).Treatment with fluvastatin ameliorated these adverse changes in model group. Conclusion Fluvastatin may promote the degradation of extracellular matrix and ameliorate extracellular matrix accumulation in glomeruli through the activation of MMP 2 and the down regnlation of TIMP 2 protein expression in 5/6 NX rats.

关 键 词：氟伐他汀 5/6肾切除术 大鼠 肾脏皮质细胞外基质 降脂作用 

分 类 号：R692[医药卫生—泌尿科学]