摘要
目的研究血管紧张素Ⅱ型受体拮抗剂缬沙坦对单侧输尿管梗阻（UUO）模型大鼠肾间质纤维化进程的作用。方法健康Wistar大鼠单侧输尿管结扎制备UUO模型,并分为模型组（n=18）、缬沙坦组（n=18,30 mg.kg-1.d-1灌胃）;以切开腹腔并游离左侧输尿管但不结扎和剪断大鼠作为对照组（n=12）。分别于术后3、102、0 d处死大鼠,全自动生化仪检测血肌酐（Scr）、尿素氮（BUN）水平,免疫组织化学方法检测肾组织骨桥蛋白（OPN）的表达,RT-PCR方法检测肾组织中转化生长因子-β1（TGF-β1）mRNA的表达。结果与对照组相比,模型组和缬沙坦组Scr及BUN自术后第10天起均显著上升（F=11.75-40.83,q=3.32-11.87,P〈0.05）;术后第3天模型组OPN及TGF-β1 mRNA表达均上调,缬沙坦组OPN自第3天亦显著增加,但TGF-β1 mRNA的表达自第10天起才显著增加（F=11.70-231.51,q=4.74-30.42,P〈0.05、0.01）。与模型组比较,缬沙坦组术后第3天OPN表达无显著差异,但TGF-β1 mRNA表达显著降低（q=3.92-15.11,P〈0.05）。结论OPN、TGF-β1参与了肾间质纤维化的进展;缬沙坦可能通过抑制OPN及TGF-β1的表达抑制UUO大鼠肾间质纤维化进程,延缓肾损害进展。
Objective To investigate the effect of angiotensin Ⅱ type 1 receptor antagonist （valsartan） on renal interstitial fibrosis caused by unilateral ureteral obstruction （UUO） in rats. Methods A UUO model in Wistar rats was made by ligating unileteral ureter. The 36 model rats were evenly divided into two groups： model group and valsartan group （30 mg·kg^-1·d^-1）. The 12 rats served as controls received only mobilization of the left ureter without cutting or ligation. The rats were sacrificed 3, 10 and 20 days after the surgery. Blood Cr and BUN were measured by automatic chemical analyzer, the expression of OPN was analyzed by immuno-histochemistry. The expression of transforming growth factor-β1 （TGF-β1） mRNA was detected by reverse transcriptionpolymerase chain reaction （RT-PCR）. Results Compared with the control, Cr and BUN in the model and valsartan groups were significantly increased from the 10th day after the operation （F= 11.75 40.83 ,q=3.32- 11.87,P〈0.05）. In model group, the expressions of OPN and TGF-β1 mRNA up-regulated; in valsartan group, OPN increased from the third clay after surgery, but TGFq31 mRNA increased starting from the 10th day （F=11.70-231.51,q=4.74-30.42,P〈0.05,0.01）. Compared with model group, the difference of OPN expression in valsartan group on the third day was not significant, but TGF β1 mRNA de creased significantly （q=3.92 15.11 ,P〈0.05）. Conclusion OPN and TGF-β1 involve in the process of interstitial fibrosis in the kidney; valsartan inhibits the interstitial fibrosis and delay renal demage of UUO in rats probably by suppressing the expressions of OPN and TGF-β1 mRNA.
出处
《青岛大学医学院学报》
CAS
2009年第5期449-452,共4页
Acta Academiae Medicinae Qingdao Universitatis
