摘要
目的:探讨局灶节段性肾小球硬化(FSGS)大鼠肾组织转化生长因子β1(TGF-β1)的表达及缬沙坦与罗格列酮干预治疗对其影响。方法:采用一侧肾切除加重复尾静脉注射阿霉素法建立局灶节段性肾小球硬化大鼠模型。随机分为正常对照组、缬沙坦治疗组、罗格列酮治疗组、缬沙坦与罗格列酮联合治疗组及模型组。动态检测24h尿蛋白定量(24hUP)及血生化值,计算内生肌酐清除率(Ccr);对肾组织进行病理形态学观察,计算肾小球硬化指数(SI)、肾小球细胞外基质与肾小球面积之比(ECM/GA),采用免疫组织化学方法检测肾组织TGF-β1的表达,并分析TGF-β1水平与SI、ECM/GA的相关性。结果:实验8周时各治疗组与模型组比较均显示24hUP降低,总蛋白、白蛋白增加,胆固醇降低,Ccr升高;SI、ECM/GA减低;免疫组化染色显示,各治疗组TGF-β1的表达均较模型组减少(P<0.05或P<0.01)。缬沙坦联合罗格列酮组尿蛋白降低、TGF-β1表达减少的作用均优于各单一药物治疗组(P<0.05或P<0.01)。结论:TGF-β1水平的变化与SI及ECM/GA同样可反映FSGS的程度,TGF-β1可以作为一个有价值的疗效评估指标。缬沙坦、罗格列酮均可能成为防治FSGS的不同靶点,缬沙坦与罗格列酮组合可以作为FSGS非激素治疗时联合用药的选择之一。
Objective：To investigate the effects of valsartan and rosiglitazone on expression of TGF-β1 in kidney tissue of focal segmental glomerulosclerosis（FSGS）rats.Methods：Rat model of FSGS was constructed with one side nephrectomy and injection of adriamycin caudal-venously respectively.Rats were randomized to normal control group,valsartan-treated group,rosiglitazone-treated group,integrated treatment group and model group.Twenty-four hours urinary protein and blood biochemical indicators were measured at the 0,4th,6th and 8th week.The values of creatinine clearance（Ccr） was calculated.Renal pathological changes were evaluated at the 8th week.Expression of TGF-β1 was detected by immunohistochemical method,and the correlation between TGF-β1 expression and the pathological changes was analyzed.Results：Twenty-four hour urinary protein in each treatment group was lower than that in model group.The values of serum total protein（TP）,albumin（ALB） increased significantly in each treatment group compared with that of model group.Meanwhile,the values of cholesterol decreased markedly,Ccr increased.The values of glomerular sclerotic index（SI） and glomerular extracellular matrix（ECM）/glomerular area（GA） were decreased significantly in each treatment group.The expression of TGF-β1 was lower in normal control group compared with that of model group.The expressions of TGF-β1 in each treatment group were decreased.Besides,there were differences between integrated treatment and other treatment group in 24 -hour urinary protein,renal pathological changes and expression of TGF-β1.Conclusion：The expression of TGF-β1 can reflect the progression of FSGS as the same as SI and ECM/GA.The integrated treatment of valsartan and rosiglitazone can be one of choices towards the treatment of FSGS except for hormone therapy.TGF-β1 may be an index of evaluating therapeutic effect.Both valsartan and rosiglitazone may be different targets to deal with FSGS.
出处
《天津医药》
CAS
北大核心
2008年第11期880-884,共5页
Tianjin Medical Journal
基金
天津市卫生局科技基金资助项目(项目编号:03ky32)
关键词
降血糖药
缬氨酸
转化生长因子Β
大鼠
hypoglycemic agents valine transforming growth factor beta rats
