福辛普利联合缬沙坦对梗阻性肾病模型幼鼠MMP-7表达的影响

目的：观察联合应用福辛普利和缬沙坦对梗阻性肾病模型（UUO）大鼠肾小管间质MMP-7表达的影响,初步探讨其在肾间质纤维化中的作用机制。方法：72只Wistar雌性幼年大鼠单侧输尿管结扎制成UUO模型,并随机分为假手术对照组（A组）、UUO模型组（B组）和福辛普利及缬沙坦联合治疗组（C组）,于模型成功后第1,2,3,4周末为实验时间点,检测各组大鼠24h尿蛋白、血尿素氮（BUN）、血肌酐（SCr）。用免疫组化法研究MMP-7在肾组织的分布、表达及变化。结果：光镜下MMP-7在对照组肾小管上皮细胞胞浆呈阴性表达,术后1周UUO组MMP-7在肾小管上皮细胞胞浆区及肾间质细胞表达,在血管内皮细胞有微量表达,2周后表达增强,4周表达最强。治疗组各周MMP-7表达较UUO组下调。结论：联合应用福辛普利和缬沙坦可通过下调MMP-7在肾组织的表达而改善肾功能,延缓肾间质纤维化的进展。

The effect of fosinopril and vaisartan on the expressions of matrix metalloproteinase-7 in the kidney of unilateral ureteral obstruction young rats

Objective： To investigate the expression of matrix metalloproteinase-7 （MMP-7） in renal tissue of young rats with unilateral ureteral obstruction（UUO） and explore its mechanism of action in the renal interstitial fi- brosis. Methods ：Seventy-two wistar female young rats were used to establish the UUO model ,and then they were di vided randomly into the three groups. That was control group （A group）, UUO model group （B group）,and group treated by fosinopril combined with valsartan （C group）. At different time points of treated for 1,2,3,4 weeks,we measured proteinuria in 24 hours of rats ,blood urea nitrogen （BUN） and serum creatinine （SCr）,detected the protein distribution and expression of MMP-7 in remnant renal tissues by the way of immunohistochemical technique. Re- sults..MMP-7 was none expressed in the tubular epithelial cells in sham group rats. In UUO untreated group rats MMP-7 was expressed in tubular epithelial and interstitial and a trace in vascular endothelial cells. MMP-7 was signif- icantly increased at 2th week,and reached its peak at 4th week. The expression was significantly downregulated in treated groups （P~0.05）. Conclusion ~Combination of fosinopril and valsartan,renal function may improved progres- sively,the progression of tubulointerstitial fibrosis may be delayed by down-regulating expression of MMP-7.