【摘要】 目的:基于Sirt5通路探讨人参皂苷Rg₁对胆汁淤积的保护作用。方法:将SD大鼠随机分成正常对照组、模型组、阳性对照组(熊去氧胆酸，100 mg·kg^-1)以及人参皂苷Rg₁低(10 mg·kg^-1)、中(20 mg·kg^-1)、高(40 mg·kg^-1)剂量组，每组6只；各组大鼠连续灌胃相应药物5 d,第3天除正常对照组外，其他各组灌胃α-萘异硫氰酸酯(ANIT,80 mg·kg^-1)建立胆汁淤积大鼠模型。造模48 h后，取肝脏记录肝重和肝重/体质量比，腹主动脉取血检测血清肝功能指标丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶（AKP）,黄疸指标总胆汁酸（TBA）及肝脏抗氧化应激因子谷胱甘肽（GSH）、超氧化物歧化酶（SOD）和氧化应激产物丙二醛（MDA）水平；采用酶联免疫吸附剂测定（ELISA）试剂盒检测血清炎症细胞因子肿瘤坏死因子（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）;采用苏木精-伊红（HE）染色检测肝脏病理变化；Western blotting检测肝组织沉默调节蛋白5（SIRT5）、核因子E2相关因子2（Nrf2）和核因子κB（NF-κB）表达。结果:与正常对照组大鼠相比，模型组大鼠的肝质量和肝质量比显著升高；肝脏病理损伤加重，肝细胞出现变性坏死，血清中ALT、AST、AKP、TBA、MDA、TNF-α、IL-6和IL-1β水平显著增加，而GSH和SOD水平显著降低；蛋白NF-κB水平显著增加，而SIRT5和Nrf2水平显著减少，差异均有统计学意义（P<0.05）。与模型组相比，阳性对照组和人参皂苷Rg₁中、高剂量组大鼠基本指标改善，肝组织病理损伤减轻，血清中ALT、AST、AKP、TBA、MDA、TNF-α、IL-6和IL-1β水平显著减少，而GSH和SOD水平显著升高；人参皂苷Rg₁、高剂量组蛋白NF-κB水平显著减少，而SIRT5和Nrf2水平显著增加，差异均有统计学意义（P<0.05）。结论:人参皂苷Rg₁对ANIT诱导的胆汁淤积大鼠具有明显的肝保护作用，该作用可能与激活Sirt5/Nrf2通路及下调NF-κB蛋白的表达有关。更多还原

【Abstract】 Objective: To investigate the protective effect of ginsenoside Rg₁ on cholestasis via Sirt5 pathway. Methods: SD rats were randomly divided into normal control group, model group, positive control group(ursodeoxycholic acid, 100 mg·kg^-1) and ginsenoside Rg₁ low-dose(10 mg·kg^-1), medium-dose(20 mg·kg^-1) and high-dose(40 mg·kg^-1) groups with 6 rats in each group. The rats were given corresponding drug for 5 days continuously in each group. On the third day, except the normal control group, other groups were given α-naphthalene isothiocyanate(ANIT, 80 mg·kg^-1) to establish cholestatic rat model. At 48 h after modeling, liver weight and liver weight/body weight ratio were recorded. Blood was taken from abdominal aorta to detect liver function indexes including alanine aminotransferase（ALT）, aspartate aminotransferase（AST） and alkaline phosphatase（AKP）, jaundice index total bile acid（TBA）, liver antioxidative stress factors glutathione（GSH） and superoxide dismutase（SOD）, and oxidative stress product malondialdehyde（MDA）. Plasma inflammatory cytokines tumor necrosis factor（TNF-α）, interleukin-6（IL-6） and interleukin-1 β（IL-1β） were detected by ELISA kits. Hematoxylin-eosin（HE） staining was used to detect the pathological changes of liver severity. The expression of Sirt5, Nrf2 and NF-κB in liver tissue was detected by Western blotting. Results: Compared with those in the normal control group, the liver weight and liver weight ratio of the model group were significantly increased; the pathological injury of liver was aggravated; the liver cells showed degeneration and necrosis; the levels of ALT, AST, AKP, TBA, MDA, TNF-α, IL-6 and IL-1β in plasma were significantly increased, while the levels of GSH and SOD were significantly decreased; NF-κB expression in ginsenoside Rg₁ high-dose group was obviously increased, while Sirt5 and Nrf2 expression were significantly decreased; all the index differences were statistically significant（P<0.05）. Compared with those in the model group, the basic indexes of rats in the positive control group and ginsenoside Rg₁ groups were improved, the pathological damage of liver tissue was relieved, the levels of ALT, AST, AKP, TBA, MDA, TNF-α, IL-6 and IL-1β in plasma were significantly decreased, while the levels of GSH and SOD were significantly increased; NF-κB expression in ginsenoside Rg₁ high-dose group was significantly decreased, while Sirt5 and Nrf2 expression was obviously increased; all the index differences were statistically significant（P<0.05）. Conclusion: Ginsenoside Rg₁ shows significant hepatoprotective activity in ANIT-induced cholestatic rats, which may be related to the activation of Sirt5/Nrf2 pathways and the down-regulation of NF-κB protein expression.更多还原