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机构地区:[1]重庆医科大学附属第一医院妇产科,400016
出 处:《肝脏》2017年第8期685-689,共5页Chinese Hepatology
基 金:国家自然科学基金资助项目(81471473);重庆市卫计委医学高端后备人才培养项目(2015XMSB0001298)
摘 要:目的比较白藜芦醇(RES)与熊去氧胆酸(UDCA)治疗妊娠期肝内胆汁淤积症(ICP)孕鼠效果,探讨RES治疗ICP的可行性及疗效。方法采用17α-乙炔雌二醇建立ICP模型,将孕13 d孕鼠70只随机分为对照组、ICP组及治疗组(LRES、MRES、HRES、UDCA、UDCA-MRES),测定用药前后TBA及ALT水平,统计各组死胎率,HE染色观察母鼠肝脏形态学改变,免疫组化及Western印迹测定肝内SIRT1及TNF-α水平。结果与ICP相比[胆汁酸水平(49.38±13.68)μmol/L,死胎率32.26%],LRES有明显降胆汁酸效果[(31.81±15.19)μmol/L,P<0.05],MRES降低死胎率效果明显(14.29%,P<0.05);UDCA-MRES联合用药存在协同降胆汁酸作用[(27.77±7.43)μmol/L,P<0.05],却比单独用药导致更高的死胎率(36.26%,P<0.05);RES能够明显增加SIRT1表达(P<0.05),降低TNF-α水平(P<0.05)。结论RES与UDCA一样具有治疗ICP的可能,但其有效剂量仍需进一步探究。Objective To compare the efficacy between resveratrol (RES) and ursodeoxycholic acid (UDCA) in the treatment of intrahepatic cholestasis of pregnancy (ICP).Methods Seventy Sprague-Dawley (SD) rats on day 13 of pregnancy were induced ICP using 17-α ethinyl estradiol, and divided into control group, ICP group and 5 treatment groups [low-dosage RES (LRES) group, middle-dosage RES (MRES) group, high-dosage RES (HRES) group, UDCA group and UDCA combined with MRES (UDCA-MRSV) group].Livers were collected for histological analysis using hematoxylin and eosin (HE) staining.Serum levels of total bile acid (TBA) and alanine aminotransferase (ALT) were measured before and after treatment in all 5 treatment groups.Stillbirth rate of each group was counted.Immunohistochemistry and western blot were applied for determining intrahepatic levels of silent information regulator 1 (SIRT1) and tumor necrosis factor-α (TNF-α).Results Compared with ICP group, LRES could obviously decrease TBA (31.81±15.19 umol/L, P<0.05), and MRES could obviously decrease the stillbirth rate (14.29%, P<0.05).UDCA-MRSV might synergistically reduce TBA level (27.77±7.43 umol/L, P<0.05), but with a higher rate of stillbirth (36.26%, P<0.05) than the single drug treatment.RES could enhance SIRT1 expression (P<0.05) and decrease TNF-α expression (P<0.05).Conclusion RES might be a potential option in treatment of ICP, of which effective dosage needs further investigation.
关 键 词:白藜芦醇 熊去氧胆酸 妊娠期肝内胆汁淤积症
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