苦参碱对UUO模型肾小管间质MMP-3、TIMP-1和FN影响的实验研究

目的 观察苦参碱对单侧输尿管梗阻（UUO）大鼠模型肾小管间质基质金属蛋白酶-3（MMP-3）、基质金属蛋白酶组织抑制物-1（TIMP-1）和纤维联结蛋白（FN）表达水平的影响，初步探讨其对小管间质纤维化的作用机制。方法 实验采用UUO肾间质纤维化模型作为研究模型，分为正常组、假UUO组、UUO组、福辛普利治疗组（F组）、苦参碱大剂量治疗组（E组）和苦参碱小剂量治疗组（D组）。运用免疫组化技术半定量分析实验第7、14d各组的MMP-3、TIMP-1和FN表达水平。结果 UUO组和治疗组的MMP-3表达水平第7、14d均低于正常组和假UUO组（P〈0．05），但三个治疗组的表达水平高于UUO组（P〈0．05）；TIMP-1和FN在正常组和假UUO组中的表达最低，而三个治疗组的表达均低于UUO组（P〈0．05）；MMP-3、TIMP-1和FN在E组与F组间的表达差异均无统计学意义（P〉0．05）；在UUO组中，MMP-3与FN、MMP-3与TIMP-1的免疫组化半定量分析均呈负相关（P〈0．01）。结论 苦参碱可以部分恢复小管间质MMP-3的表达水平，降低TIMP-1和FN的表达水平．从而延缓肾小管间质纤维化的进程。

Effect of Matrine on Regulating Renal Tubulointerstitial Expression of MMP-3, TIMP-1 and FN

Objective To explore the effect and mechanism of matrine on regulating renal tubulointerstitium expression of MMP-3,TIMP-1 and FN.Methods Seventy male SD rats were randomly allocated to five groups: normal group,shame UUO group,UUO group,UUO group treated with fusinopril(F group),UUO group treated with large dose of matrine(E group) and UUO group treated with small dose of matrine(D group).The expression levels of MMP-3,TIMP-1 and FN of the rats were determined with immunohistochemistry at 7,14 days of the experiment.Results The expression levels of MMP-3 of the rats in the UUO group and treatment groups decreased significantly compared with the normal group and shame UUO group(P<0.05).The treatment groups had higher expression of MMP-3 than that of the UUO group(P<0.05).The expression levels of TIMP-1 and FN of the rats in the normal group and shame UUO group were amongst the lowest.The treatment groups had lower expression of TIMP-1 and FN than that of the UUO group(P<0.05).No significant difference of expression of MMP-3,FN and TIMP-1 were found between E group and F group(P>0.05).The expression level of MMP-3 was negatively correlated with those of TIMP-1 and FN in the UUO group(P<0.01).Conclusion Matrine decreases the expression of TIMP-1 and FN in the tubulointerstitium and increases the expression of MMP-3,which would delay the progression of renal tubulointerstitial fibrosis.