The effect of ginsenoside Rg1 on intrahepatic cholestasis of pregnancy in rats by regulating the Nrf2/ARE signaling pathway
Objective To investigate the effect of ginsenoside Rg1(GRg1)on intrahepatic cholestasis of pregnancy(ICP)in rats by regulating the nuclear factor erythroid-2-related factor 2(Nrf2)/antioxidant response ele-ment(ARE)signaling pathway.Methods Female pregnant SD rats were randomly separated into a Normal group,an ICP model group(Model group),a low-dose GRg1 group(GRg1-L group,20 mg/kg GRg1),a high-dose GRg1 group(GRg1-H group,40 mg/kg GRg1),and a high-dose GRg1+Nrf2 inhibitor all trans retinoic acid(ATRA)group(GRg1-H+ATRA group,40 mg/kg GRg1+10 mg/kg ATRA),with 12 rats in each group.The combination in-jection of estradiol benzoate and progesterone was used to establish a rat ICP model.After administration,the ELISA method was applied to detect the levels of total bilirubin(TBIL),alanine aminotransferase(ALT),aspartate amino-transferase(AST),alkaline phosphatase(ALP),total bile acid(TBA),tumor necrosis factor-α(TNF-α),inter-feron-γ(IFN-γ),interleukin-1β(IL-1β)in rat serum,and superoxide dismutase(SOD)and malondialdehyde(MDA)in liver tissue.HE staining was applied to observe the pathological changes in rat liver tissue slices.Western Blot was applied to detect the expression of Nrf2/ARE signaling pathway related proteins in rat liver tissue.Results Compared with the normal group,the serum ALT,AST,TBIL,ALP and TBA levels in the model group were obvi-ously increased(P＜0.05).The inflammatory factors TNF-α,IFN-γ,IL-1β and liver tissue MDA level in the nor-mal group[(248.26±27.64)pg/mL,(153.68±18.47)pg/mL,(189.53±23.21)pg/mL and(2.89±0.36)nmol/mg,re-spectively]were significantly higher than those in the model group rats[(53.47±8.69)pg/mL,(24.72±2.94)pg/mL,(46.89±6.82)pg/mL and(1.05±0.14)nmol/mg,respectively](P＜0.05).The SOD level,Nrf2 and ARE protein ex-pression levels in liver tissue of normal group[(53.18±8.77)U/mg,0.34±0.03 and 0.40±0.04,respectively]were significantly lower than those in the model group rats[(128.95±16.34)U/mg,0.87±0.09 and 0.94±0.09,respective-ly](P＜0.05).Compared with the Model group,the changes in relevant indicators in the GRg1-L and GRg1-H groups were opposite to the above(P＜0.05).Nrf2 inhibitors reduced the therapeutic effect of GRg1 on ICP rats.Conclu-sion GRg1 may have a certain therapeutic effect on rat with ICP by activating the Nrf2/ARE signaling pathway.
Ginsenoside Rg1Nuclear factor erythroid-2-related factor 2/antioxidant response element signaling pathwayIntrahepatic cholestasis of pregnancyRat
阮俊霞、王成群、杨柏柳、WANG Zhu
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北京圣宝妇产医院药剂科,北京 100192
北京圣宝妇产医院妇产科,北京 100192
Department of Pharmacy,Beijing Shengbao Maternity Hospital,Beijing 100192,China
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