苦参碱对单侧输尿管梗阻模型大鼠肾小管间质纤维化的影响

Experimental Study on Effect of Matrine in Alleviating Renal Tubulointerstitial Fibrosis in Unilateral Ureteral Obstruction Model

目的观察苦参碱对单侧输尿管梗阻(unilateralureteralobstruction,UUO)模型大鼠肾小管间质的基质金属蛋白酶3(matrixmetalloproteinase3,MMP3)、基质金属蛋白酶组织抑制物1(tissueinhibitorofmetalloproteinase1,TIMP1)、纤维连接蛋白(fibronectin,FN)、结缔组织生长因子(connectivetissuegrowthfactor,CTGF)和α平滑肌肌动蛋白(αsmoothmuscleactin,αSMA)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(苦大组)和苦参碱小剂量治疗组(苦小组)。运用免疫组化技术半定量分析实验第14天各组MMP3、TIMP1、FN、CTGF和αSMA的表达水平。结果UUO组和治疗组的MMP3在UUO模型第14天均显著低于正常组和假UUO组(P<0.05),但3个治疗组的表达水平明显高于UUO组(P<0.05);TIMP1、FN、CTGF和αSMA在正常组和假UUO组中的表达最低,而3个治疗组的表达均低于UUO组(P<0.05);各指标在苦大组与F组间的表达均无统计学差异(P>0.05)。结论苦参碱可以部分恢复小管间质MMP3的表达,同时降低TIMP1、FN、CTGF和αSMA的表达,从而延缓肾小管间质纤维化的进程。

Objective To observe the effects of matrine on renal tubulointerstitial fibrosis in unilateral ureteral obstruction （UUO） rat model and to explore its mechanisms. Methods Model rats of UUO were established and randomly divided into 6 groups： the normal group, the sham group, the UUO model group, the fusinopril treated group （F group）, the high dose and low dose matrine treated groups （HM and LM）. The expressions of matrix metalloproteinase-3 （MMP-3）, tissue inhibitor of metalloproteinase-1 （TIMP-1）, fibronectin （FN）, connective tissue growth factor （CTGF） and a-smooth muscle actin （α-SMA） were determined semi-quantitatively by immunohistochemistry on the 14th day. Results The expression of MMP-3 in the UUO model rats was significantly lowed on the 14th day, compared with that in rats not modeled in the normal and the sham groups （P〈0.05）, but it was higher in the three treated groups than that in the UUO model group （P〈 0.05）; the expressions of TIMP-1, FN, CTGF and α-SMA were lower in the normal group and sham UUO group than those in all the UUO model groups, while they were lower obviously in the three treated groups than those in the UUO model group （P 〈 0.05） ; there was no significant difference in the above-mentioned indexes between HM group and F group （P 〈 0.05）. Conclusion Matrine could decrease the expressions of TIMP-1, FN, CTGF and a-SMA in the tubulointerstitium, and partly restore the expression of MMP-3, so as to delay the progression of renal tubulointerstitial fibrosis.