三七皂苷R1 对肝纤维化大鼠TGF-beta1/Smad3信号的影响

目的:探讨SD大鼠肝纤维化后肝组织及血清中转化生长因子-β1(Transforming Growth Factor-β1,TGF-β1)及Smad3的表达和变化,以及三七皂苷R1对肝纤维化的保护作用。方法:72只健康雄性SD大鼠分为对照组、二甲基亚硝胺(NDMA)组和三七皂苷R1组,再按不同时间点分为1、2、4周,3个亚组,每个亚组8只动物。NDMA组采用NDMA 2 m L/kg腹腔注射,三七皂苷R1组同时静脉注射三七皂苷R1,剂量为100 mg/kg体重,对照组注射等量的生理盐水。在各组的不同时间点采用RT-PCR及ELISA技术检测肝组织及血清中TGF-β1、Smad3的表达及变化。结果:1、TGF-β1、Smad3 m RNA及蛋白在各组中均有表达。2、对照组各时间点比较均无统计学意义(P>0.05)。NDMA组中,随着损伤时间的延长,TGF-β1、Smad3 m RNA及蛋白的表达逐渐上调,且各时间点与对照组比较有统计学意义(P<0.05)。而三七皂苷R1组TGF-β1、Smad3 m RNA及蛋白在各时间点均较NDMA组表达下调,有统计学意义(P<0.05)。结论:1、TGF-β1/Smad3信号参与了肝纤维化的发生和发展过程,且随损伤的逐渐加重,表达越高。2、三七皂苷R1可降低肝组织中TGF-β1/Smad3信号的表达,减轻肝细胞的纤维化,发挥保护肝组织损伤的作用。

The Effect of Notoginsenoside R1 on TGF-beta1/smad3 Signal Pathway in Hepatic Fibrosis Rats

Objective:To investigate the expression of transforming growth factor-beta1 (TGF-beta1) and Smad3 in liver and serum after hepatic fibrosis, and the protective effect of Notoginsenoside R1 on hepatic fibrosis.Methods:72 healthy male SD rats were randomly divided into control group, NDMA group and Notoginsenoside R1 group, according to the different time points of 1, 2, 4 weeks, 3 subgroups, each subgroup 8 animals. For NMDA group, NMDA was administrated by intraperitoneal injection (2 mL/kg); and for Notoginsenoside R1 group, Notoginsenoside R1 was administrated by intravenous injection with a dose of 100 mg/kg and the animals of control group was injected with equal amount normal saline. The expression of TGF-beta1 and Smad3 in liver tissues and serum was detected at different time points using ELISA and RT-PCR.Results:Expression of TGF-beta1 and Smad3 protein and mRNA was detectable in all groups. In the control group, the expression of TGF-beta1 and Smad3 at different time points had no statistical significance (P>0.05). Compared with that in the control group, the expression of TGF-beta1 and Smad3 protein and mRNA in NMDA group gradually increased at each time point with the injury, and showed statistical significance (P<0.05). While in Notoginsenoside R1 group, expression of TGF-beta1 and Smad3 at each time point was down-regulated, with statistical significance (P<0.05) compared with that in the NDMA group.Conclusion:TGF-beta1/Smad3 signal was involved in the occurrence and development of liver fibrosis, and with the aggravation of injury, the expression of TGF-beta1 and Smad3 gradually increased. Notoginsenoside R1 could reduce TGF-beta1/Smad3 signal in liver tissues, then reduce liver fibrosis and protect the liver frominjury.