温阳活血方对单侧输尿管梗阻模型大鼠肾组织基质金属蛋白酶抑制剂-1和基质金属蛋白酶-3表达的影响  

Effect of WenyangHuoxueFang on expression of MMP-3 and TIMP-1 in kidney of rats with unilateral ureteral obstruction(UUO)

作　　者：曹微[1] 李均[2] 师晶丽[1] 

机构地区：[1]中山大学附属第五医院,珠海519000 [2]遵义医学院附属第五医院,珠海519000

出　　处：《中华中医药杂志》2008年第3期225-228,共4页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：贵州省省长基金资助项目(No.C-263);遵义医学院博士启动基金资助(No.200407)

摘　　要：目的:观察温阳活血方对实验大鼠肾间质纤维化的保护作用并探讨其作用机制。方法:实验采用单侧输尿管梗阻大鼠模型,随机分为温阳活血组、福辛普利组、模型组,并设假手术组。观察梗阻侧肾脏组织形态学改变,运用ELISA法测大鼠尿视黄醇结合蛋白(retinol binding protein,RBP)水平,免疫组化半定量法分析基质金属蛋白酶-3(marix metalloproteinases,MMP-3)、基质金属蛋白酶抑制剂-1(tissue inhibitor of metallo-proteinases,TIMP-1)的表达水平。结果:造模各组与假手术组相比均呈不同程度的病理损害。造模各组RBP水平均有所增高,温阳活血组、福辛普利组RBP水平明显低于模型组(P<0.05),两组间无明显差异(P>0.05)。模型组的MMP-3、TIMP-1表达水平均增高,而TIMP-1增高程度高于MMP-3。温阳活血组、福辛普利组MMP-3的表达水平高于模型组(P<0.05);但TIMP-1的表达水平低于模型组(P<0.05);MMP-3、TIMP-1在两个治疗组间的表达差异均无统计学意义(P>0.05)。结论:温阳活血方可能通过抑制TIMP-1的表达,恢复MMP-3表达,以此来调节MMP-3/TIMP-1的比例,减轻RBP的排泄,从而保护肾小管功能,减轻间质纤维化的进展。Objective： To observe the protective effect of WenyangHuoxueFang on renal interstitial fibrosis in rats and try to explore the mechanism. Methods： The renal obstruction model of rats was established by unilateral ureteral obstruction（ UUO） ,and then they were divided into four groups randomly, including UUOW group（treated with WenyangHuoxueFang）, UUOF group（treated with Fosinopril）, UUO group and the sham-operation group. The morphological changes of kidney tissue were observed, the level of RBP was detected by ELISA, the expression of MMP-3 and TIMP-1 was detected by immuno-histochemistry. Results： Compared with the sham-operation group, there were different degrees of kidney lesions in UUO group and the treatment groups. The level of RBP in UUO group was significantly higher than that in sham-operation group, Compared with UUO group, the RBP expression in UUOF group and U UOW group was significantly lower（ P 〈 0.05）. There was no significant difference between these two groups（ P 〉 0.05）. The expressions of MMP-3 and TIMP-1 in UUO group were increased, and the amplitude of increasing expression of TIMP-1 was higher than that of MMP-3. The treatment groups had higher expression of MMP-3（P 〈 0.05）but lower expression of TIMP-1（P 〈 0.05）than that of the UUO group. However, the expression of TIMP-1 and M MP-3 did not show much difference between the two treatment groups. Conclusion ： WenyangHuoxueFang can protect the function of renal tubule and delay the progression of renal tubulointerstitial fibrosis probably by inhibiting the expression of TIMP-1 and increasing the expression of M MP-3 in the tubulointerstitium , which regulates the percentage of M MP-3/TIMP-1, so as to down regulate the level of RBP.

关 键 词：肾间质纤维化 温阳活血方 MMP-3 TIMP-1 

分 类 号：R285.5[医药卫生—中药学]