阿托伐他汀对单侧输尿管梗阻大鼠肾间质中TGF-β_1及TIMP-1表达的影响  

Expression of TGF-β_1 and TIMP-1 and Effects of Atorvastatin in Rats After Unilateral Ureteral Obstruction

作　　者：欧三桃[1] 陈明[1] 彭红霞[1] 张超[1] 

机构地区：[1]泸州医学院附属医院肾病内科

出　　处：《中国中西医结合肾病杂志》2004年第10期570-573,共4页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：四川省教育厅科研基金资助项目 (No .2 0 0 0 -11)

摘　　要：目的 :研究单侧输尿管梗阻 (UUO)后转化生长因子 - β1(TGF - β1)、组织金属蛋白酶抑制因子 - 1(TIMP - 1)的表达变化 ,从而探讨肾间质纤维化的发生机制及阿托伐他汀的保护作用。方法 :将 4 5只大鼠随机分为假手术组、模型组和阿托伐他汀组 (简称治疗组 )。采用UUO模型 ,在术后 5d、10d、15d每组各取 5只处死 ,留取空腹血清检测血脂浓度和肾功能 ,左肾组织行HE和Masson染色 ,动态观察肾脏病理学变化 ,并用免疫组化方法测定肾组织中TGF - β1、TIMP - 1的表达变化。结果 :各组大鼠血脂浓度无统计学差异。模型组大鼠肾间质中TGF - β1、TIMP - 1的表达随梗阻时间的延长逐渐增多 ,与假手术组相比有统计学差异 (P <0 .0 0 1)。治疗组与模型组相比 ,各时间点TGF - β1、TIMP - 1的表达下调有统计学差异 (P <0 .0 0 1) ,且两者之间存在一定的相关性 (r =0 .37,P <0 .0 1)。结论 :阿托伐他汀可能通过阻断肾组织中TGF - β1的作用和抑制TIMP - 1的过度表达而发挥其肾保护作用 。Objective:To study the mechanism of renal interstitial fibrosis after unilateral ureteral obstruction and the renoprotective effect of atorvastatin.Methods:Forty-five rats were randomly assigned to shame operation group,operation group and atorvastatin(10 mg·kg -1 ·d -1 ) treatment group after unilateral ureteral obstruction. Fasting vein blood sample was collected from each rat just before nephrectomy to measure the level of serum lipid,urea and creatinine.Renal tissues were examined by HE and Masson stain.Immunhistochemistry was performed for transforming growth factor-β 1(TGF-β 1)、tissue inhibitor of metalloproteinase-1(TIMP-1) in the renal interstitum.Results:There is no statistical siginificance among the level of serum lipid in the three groups.In comparison with shame operation group,the expression of TGF-β 1 and TIMP-1 in the interstitum of operation group siginificantly increased(P<0.001).In comparison with operation group,atorvastatin siginificantly decreased the expression of TGF-β 1 and TIMP-1 (P<0.001).There is positive correlation between TGF-β 1 and TIMP-1(r=0.37).Conclusion:Atorvastatin may protect renal by inhibiting over-expression of TGF-β 1 and TIMP-1 and independent of its cholesterol-lowing effect.

关 键 词：TIMP-1 TGF-β1 阿托伐他汀 表达 大鼠 肾间质 单侧输尿管梗阻 肾组织 治疗组 血脂浓度 

分 类 号：R965[医药卫生—药理学]