泽兰对单侧输尿管梗阻大鼠肾间质纤维化的影响

Effect of Lycopus on Expression of Renal Interstitial Fibrosis in Rats with Unilateral Ureteral Obstruction

目的:观察泽兰对单侧输尿管梗阻(UUO)大鼠肾小管间质纤维化及肾功能的影响,并探讨其可能机制。方法:采用UUO大鼠模型,将40只雄性SD大鼠随机分为4组,每组10只,即假手术组、模型组、泽兰组和厄贝沙坦组,术后当天每日1次灌胃,假手术组和模型组每日给予5ml生理盐水,泽兰组按6g·kg-1.d-1给药,厄贝沙坦组按厄贝沙坦10mg·kg-1.d-1给药,14d处死大鼠,收集血清测定血肌酐(Scr)和尿素氮(BUN),进行HE染色观察肾组织病理改变,用Masson染色进行肾间质纤维化评估,应用免疫组织化学方法检测梗阻侧肾组织结缔组织生长因子(CTGF)和肝细胞生长因子(HGF)的表达。结果:模型组与两给药组大鼠血清Scr、BUN上升,与假手术组比较有统计学差异(P<0.05)。HE染色后光镜下可见假手术组大鼠肾小球及肾小管间质正常,模型组大鼠肾小管间质区域可见炎细胞浸润增多,细胞外基质成分增多;泽兰组大鼠间质内炎细胞则呈小灶性浸润。Masson染色显示,模型组阳性染色面积占整个视野面积百分比结果与假手术组相比,具有统计学差异(P<0.01);泽兰组与模型组相比,具有统计学意义(P<0.05)。模型组CTGF的表达增加,与假手术组相比有统计学差异(P<0.01);泽兰组与模型组相比,CTGF的表达下降,而HGF的表达增高,有统计学差异(P<0.05)。泽兰组与厄贝沙坦组结果相似(P>0.05)。结论:泽兰能通过下调CTGF的表达及增加HGF的表达而延缓UUO大鼠肾间质纤维化。

Objective： To study the expression of connective tissue growth factor（CTGF） and hepatocyte growth factor （HGF） during the progression of renal interstitial fibrosis in rat unilateral ureteral obstruction（UUO） model and the effect of Lycopus, then to explore the mechanisms. Methods： The obstructive nephropathy model was established by unilateral ureteral obstruction （UUO）, forty rats were randomly assigned into sham group, operation group（UUO group）, treatment group by Lycopus （UUO ＋ Lycopus） and treatment group by irbesartan （UUO ＋ irbesartan）. AT 14th day, renal function and histopathological changes were evaluated. The expressions CTGF of and HGF in renal tissue was examined by immunohistochemistry. The results were analyzed semi - quantitiatively with the pathological immage analysis system. The experimental data was demonstraed in mean standard deviation. The analysis of variance were used to the signifcance test by SPSS13.0. Results：Compared with sham group,UUO group and Lycopus group on BUN ＆Scr have distinctly distinction （ P 〈 0.05 ）. After HE dyeing, we can see the renal tubules of sham group rats are normal under light microscope, the phlegrnasias infiltrated in the renal tubules of UUO group rats, ECM are increased; in Lycopus group the renal tubules are lightrange broaden. Masson dyeing display that, the masc dyeing areas percentage to whole visual field in UUO group are increased obviously compared with sham group （P〈0.01） ,Lycopus group compared to UUO group have distinctly distinction（P 〈 0.05 ）. In comparison with the sham group, the expression of CTGF significantly increase （ P 〈 0.05 ） in UUO group. In comparison with the UUO group, the expression of CTGF reduce （ P 〈 0.05 ） and the expression of HGF increase （P 〈 0.05） in Lycopus groups. But between Lycopus groups and irbesartan group are no distinctly distinction （P 〉 0.05）. Conclusion： Lycopus may protect the kidney by down - regulating the expression of CTGF and up - regulating the expression of HGF in progression of renal interstitial fibrosis.