Xie Xi-sheng, Liu Heng-chuan, Yang Man, Zuo Chuan, Deng Yao, Fan Jun-ming
Department of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041, China.
Chin J Integr Med. 2009 Apr;15(2):133-40. doi: 10.1007/s11655-009-0133-9. Epub 2009 Apr 29.
To investigate the possible protective effect and mechanism of ginsenoside Rb1 against oxidative damage and renal interstitial fibrosis on rats with unilateral ureteral obstruction (UUO).
In total, 80 male rats were randomly divided into 4 groups, 20 in each group: the sham operated group (SOR), UUO group, UUO with ginsenoside Rb1 treatment group (treated with intraperitoneal injection of 50 mg/ kg daily) and UUO with Losartan treatment group (as the positive control, treated with 20 mg/kg by gastrogavage per day). The rats were randomly sacrificed on day 3, 7 and 14 after surgery, respectively. The histopathologic changes of renal interstitial tissues were observed with Masson staining. The mRNA of transforming growth factor beta 1 (TGF-beta 1), collagen I and fibronectin were reversed transcribed and quantified by Real-time PCR. Enzyme-linked immunosorbent assay was used to quantitatively detect TGF-beta 1 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. P47phox protein expression was assessed by immunohistochemistry and Western blot analysis.
In the UUO model, the obstructed kidney showed typical features of progressive renal tubulointerstitial fibrosis, and the levels of TGF-beta1, collagen I and fibronectin increased (P<0.05). As compared with the UUO group, ginsennoside Rb1 significantly inhibited the interstitial fibrosis including tubular injury and collagen deposition, and decreased the levels of TGF-beta1 (P<0.05). Ginsenoside Rb1 also inhibited the heme oxygenase (HO-1) and 8-OHdG, two markers of oxidative stress (P<0.05). Moreover, ginsenoside Rb1 suppressed the expression of p47phox, a subunit of nicotinamide adeninedinucleotide phosphate (NADPH) oxidase (P<0.05).
Ginsenoside Rb1 can obviously inhibit renal interstitial fibrosis in rats with UUO, its mechanism possibly via against the oxidative damage and suppressing TGF-beta1 expression.
探讨人参皂苷Rb1对单侧输尿管梗阻（UUO）大鼠氧化损伤及肾间质纤维化的可能保护作用及机制。
将80只雄性大鼠随机分为4组，每组20只：假手术组（SOR）、UUO组、人参皂苷Rb1治疗的UUO组（每日腹腔注射50 mg/kg）和氯沙坦治疗的UUO组（作为阳性对照，每日灌胃20 mg/kg）。分别于术后第3、7和14天随机处死大鼠。采用Masson染色观察肾间质组织的组织病理学变化。通过实时PCR反转录并定量检测转化生长因子β1（TGF-β1）、I型胶原和纤连蛋白的mRNA。采用酶联免疫吸附测定法定量检测TGF-β1和8-羟基-2'-脱氧鸟苷（8-OHdG）水平。通过免疫组织化学和蛋白质印迹分析评估P47phox蛋白表达。
在UUO模型中，梗阻侧肾脏呈现进行性肾小管间质纤维化的典型特征，TGF-β1、I型胶原和纤连蛋白水平升高（P<0.05）。与人参皂苷Rb1治疗的UUO组相比，人参皂苷Rb1显著抑制包括肾小管损伤和胶原沉积在内的间质纤维化，并降低TGF-β1水平（P<0.05）。人参皂苷Rb1还抑制氧化应激的两个标志物血红素加氧酶（HO-1）和8-OHdG（P<0.05）。此外，人参皂苷Rb1抑制烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶亚基p47phox的表达（P<0.05）。
人参皂苷Rb1可明显抑制UUO大鼠的肾间质纤维化，其机制可能是通过对抗氧化损伤和抑制TGF-β1表达。
