苦参碱对肾小管间质MMP-3和TIMP-1的影响

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MMP-3和TIMP-1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:实验分为正常组(A组)、假UUO组(B组)、UUO组(C组)、苦参碱低剂量治疗组(D组)、苦参碱高剂量治疗组(E组)和福辛普利对照组(F组).运用免疫组化技术观察第7 d、14 d各组大鼠的MMP-3和TIMP-1表达水平,采用Pearson分析方法分析二者在C组中的相关性.结果:在C组和各药物组中,MMP-3表达水平在第7 d、14 d均显著低于A组和B组(P<0.05),但各药物组的表达水平明显高于C组(P<0.05);TIMP-1在A组和B组的表达最低,各药物组的表达水平显著低于C组(P<0.05);MMP-3 和TIMP-1在E组与F组间均无统计学差异(P>0.05);MMP-3与TIMP-1在C组的免疫组化半定量分析呈显著负相关(P<0.01).结论:苦参碱可部分恢复肾小管间质MMP-3的表达,降低TIMP-1的表达,延缓肾小管间质纤维化的进程.

Experimental Investigation about Effects of Matrineon Expression of MMP-3 and TIMP-1 in Tubulointerstitium

Objective:The study is to observe the effects of the matrine on the renal tubulointerstitium, to explore its action mechanism.Methods:Seventy male SD rats were randomly divided into 5 groups: normal group(A group), shame UUO group(B group), UUO group(C group), UUO group treated with the low lose of matrine (D group), UUO group treated with the high lose of matrine (E group) and UUO group treated with the fosinopril (F group). The expression levels of MMP-3 and TIMP-1 in all the groups were determined by immunohistochemistry at 7,14 days.Results:The expression levels of MMP-3 in the C group and treatment groups were significantly decreased compared to A group and B group (P<0.05), but they were higher in the treatment groups than that in C group (P<0.05);while the expression levels of TIMP-1 in A group and B group were the lowest in the study,they were dominantly lower in the treatment groups than in C group (P<0.05);as to MMP-3 and TIMP-1,there was no significant difference between E and F group (P<0.05). The expression level of MMP-3 was completely negatively correlated with that of TIMP-1 in C group (P<0.01).Conclusion:Matrine could decrease levels of TIMP-1 and increase level of the MMP-3 in the renal tubulointerstitium,which might delay the progression of the renal tubulointerstitial fibrosis.