【摘要】 目的动态观察黄芪(AM)对单侧输尿管梗阻(UUO)所致大鼠肾小管间质纤维化的拮抗作用和肝细胞生长因子(HGF)表达的影响。方法SD大鼠随机分为假手术组(SOR组)、UUO组和UUO+AM治疗组(AM组)。在造模后3、7、14d处死动物,观察肾脏病理改变。采用免疫组化方法检测肾组织中α-平滑肌肌动蛋白(α-SMA)、HGF表达。实时荧光定量RT-PCR检测大鼠HGF mRNA和α-SMA mRNA表达量。Wester nblot检测大鼠HGF及其受体C-met蛋白表达量。结果与SOR组相比,各时间点UUO大鼠肾脏病理损害进行性加重,AM治疗后可明显减轻UUO大鼠肾小管损伤及肾间质纤维化程度(P<0.05)。随着梗阻时间的延长,UUO大鼠肾组织α-SMA表达逐渐增加;HGF及其受体C-met呈现先升高后下降的表达规律,在UUO术后第7d达高峰,此后大幅回落;与UUO组各对应时间点比较,AM治疗后可使肾组织中的HGF及其受体C-met表达显著增高,α-SMA表达明显降低(P<0.05)。结论AM可能通过诱导HGF及其受体C-met的表达,负性调控肾小管上皮细胞转分化,减轻肾间质纤维化。更多还原

【Abstract】 Objective To study the effect of Astragalus mongholicus(AM)on the expression of hepatocyte growth factor(HGF)in SD rats with unilateral ureteral obstruction(UUO)and to elucidate the mechanisms underlying the renoprotective effects of AM.Methods Fifty four Sprague-Dawley rats were randomly divided into 3 groups:sham-operation group(SOR),UUO group(UUO)and UUO + AM group(AM).After administration of AM〔10 g/(kg·d)〕 for 3,7 and 14 days,the histological changes of renal interstitial tissues were observed dynamically,and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections.The protein expression of HGF and α-smooth muscle actin(α-SMA)was measured by immunohistochemistry.The mRNA expression of HGF and α-SMA were determined by real-time PCR.The expression of HGF and its receptor(C-met)were assessed by Western blot.Results Renal damage was exacerbated and the expression of α-SMA was significantly increased in UUO group compared with those of SOR group(P<0.05)at each time point.HGF and C-met expression peaked at the 7th day after UUO and then decreased greatly.After AM intervention,tubular impairment and interstitial fibrosis were alleviated,up-regulations of α-SMA expressions was significantly suppressed,whileas the expression of HGF and C-met were significantly increased when compared with UUO group(P<0.05)at each time point.Conclusion AM can ameliorate renal interstitial fibrosis induced by UUO in rats.The mechanisms of its antifibrotic effects may be related with the up-regulation of HGF and C-met expression,and the suppression of tubulo-epithelial mesenchymal transdifferentiation in renal intersitial progress.更多还原