人参皂苷Rg1抑制小鼠肝细胞氧化应激和炎症减轻阿霉素诱导的肝损伤研究

Ginsenoside Rg1 attenuates adriamycin-induced liver injury by inhibiting oxidative stress and inflammation in mouse hepatocytes

目的 探讨人参皂苷Rg1抑制小鼠肝细胞的氧化应激和炎症,从而减轻阿霉素(DOX)诱导的肝损伤的机制。方法 小鼠皮下注射DOX(15 mg/kg),建立肝损伤模型并且给予人参皂苷Rg1低剂量(10 mg/kg)和高剂量(50 mg/kg)治疗,苏木精-伊红(H&E)染色探讨人参皂苷Rg1对于小鼠肝组织的影响;体内AST、ALT的表达情况;ELISA检测炎症因子的表达情况;CCK8检测Rg1对DOX诱导的AML12细胞损伤的影响;通过检测体内外ROS、MDA、GSH、SOD的表达情况探讨Rg1对DOX诱导的氧化应激的调控作用;通过Western blot检测Nfr2/ARE通路中Nrf2、HO-1、NQO1蛋白的表达情况。结果 通过H&E染色结果和AST、ALT的表达证明肝损伤模型的成功建立;ELISA检测结果显示Rg1可降低DOX诱导的促炎因子IL-6的表达,以及增加抗炎因子IL-10的表达;CCK8检测结果显示Rg1可缓解DOX引起的肝细胞损伤;另外,Rg1可以调控DOX诱导的肝损伤引起的氧化应激;Western blot检测结果显示Rg1干预后,Nfr2/ARE通路中Nrf2、HO-1、NQO1的表达水平升高,提示其通过激活Nfr2/ARE通路改善DOX诱导的肝损伤。结论 人参皂苷Rg1通过激活Nrf2/ARE信号通路,抑制氧化应激和炎症反应改善DOX诱导的肝脏损伤。

Objective To investigate the mechanism of ginsenoside Rg1 in alleviating adriamycin(DOX)-induced liver injury by inhibiting oxidative stress and inflammation in mouse hepatocytes. Methods A mouse model of liver injury was established by subcutaneous injection of DOX(15 mg/kg),and ginsenoside Rg1 was given at low(10 mg/kg) and high(50 mg/kg) doses. Hematoxylin-eosin(H&E) staining was used to investigate the effect of ginsenoside Rg1 on liver tissue in mice. The expression of AST and ALT in vivo;ELISA was used to detect the expression of inflammatory factors. CCK8 assay was used to detect the effect of Rg1 on DOX-induced AML12 cell damage. The regulatory effect of Rg1 on DOX-induced oxidative stress was explored by detecting the expression of ROS,MDA,GSH and SOD in vivo and in vitro. Western blot was used to detect the expression of Nrf2,HO-1,and NQO1 proteins in the Nfr2/ARE pathway. Results The model of liver injury was successfully established by H&E staining and the expression of AST and ALT. The results of ELISA showed that Rg1 reduced the expression of pro-inflammatory cytokine IL-6 and increased the expression of anti-inflammatory cytokine IL-10 induced by DOX. CCK8 assay showed that Rg1 could alleviate DOX-induced hepatocyte injury. In addition, Rg1 regulated oxidative stress in DOX-induced liver injury;Western blot results showed that the expression levels of Nrf2,HO-1,and NQO1 in the Nfr2/ARE pathway were increased after Rg1 intervention, suggesting that the activation of Nfr2/ARE pathway could improve DOX-induced liver injury. Conclusion Ginsenoside Rg1 can alleviate DOX-induced liver injury by activating Nrf2/ARE signaling pathway and inhibiting oxidative stress and inflammatory response.