Zuo Chuan, Xie Xisheng, Deng Yao, Fan Junming
Department of Nephrology, West China Hospital of Sichuan University, Chengdu 610041, China.
Wei Sheng Yan Jiu. 2008 Sep;37(5):566-70.
To study the effect of Astragalus mongholicus (AM) on renal interstitial fibrosis caused by unilateral ureteral obstruction (UUO) in rats in order to elucidate the mechanisms underlying the renoprotective effects of AM.
54 Sprague-Dawley rats were randomly divided into 3 groups: sham-operation group (Sham), the UUO group(UUO) and UUO + AM group (AM). The rats were treated at the doses of 10 g/(kg X d) AM for 3, 7 and 14 days, the dynamic histological changes of renal interstitial tissues were observed and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The expressions of transforming growth factor-beta1 (TGF-beta1) and hepatocyte growth factor (HGF) were measured by immunohistochemistry staining sections. The mRNA of HGF and TGF-beta1 were reverse transcribed and quantified by real-time PCR. The expressions of HGF and TGF-beta1 protein were assessed by Western blot.
Renal damages were exacerbated and the expressions of TGF-beta1 were significantly increased in UUO group in comparison with those of Sham group (P < 0.05) at each time point. HGF expression increased initially and peaked at the day of 7 after UUO and then decreased greatly. The tubular impairment and interstitial fibrosis were alleviated, up-regulations of expressions of TGF-beta1 were significantly suppressed, while expressions of HGF were significantly increased in UUO + AM group in comparison with UUO group (P < 0.05).
AM could ameliorate renal interstitial fibrosis induced by UUO in rats. The mechanisms of antifibrotic effects of AM may be associated with up-regulation of HGF expression and down-regulation of TGF-beta1 expression in renal intersitial progress.
研究黄芪对大鼠单侧输尿管梗阻(UUO)所致肾间质纤维化的影响,以阐明黄芪肾脏保护作用的机制。
将54只Sprague-Dawley大鼠随机分为3组:假手术组(Sham)、UUO组(UUO)和UUO+黄芪组(AM)。以10 g/(kg×d)的剂量给予大鼠黄芪处理3、7和14天,观察肾间质组织的动态组织学变化,并在HE和Masson染色的组织切片上对包括肾小管损伤和间质纤维化在内的肾损伤进行定量分析。通过免疫组织化学染色切片检测转化生长因子-β1(TGF-β1)和肝细胞生长因子(HGF)的表达。通过实时PCR对HGF和TGF-β1的mRNA进行逆转录和定量分析。通过蛋白质印迹法评估HGF和TGF-β1蛋白的表达。
与假手术组相比,UUO组在各个时间点的肾损伤均加重,TGF-β1的表达显著增加(P<0.05)。HGF表达最初增加,并在UUO后第7天达到峰值,然后大幅下降。与UUO组相比,UUO+黄芪组的肾小管损伤和间质纤维化减轻,TGF-β1表达的上调受到显著抑制,而HGF的表达显著增加(P<0.05)。
黄芪可改善大鼠UUO诱导的肾间质纤维化。黄芪抗纤维化作用的机制可能与肾间质进程中HGF表达上调和TGF-β1表达下调有关。