妊娠期肝内胆汁淤积症大鼠肝损伤及其肠道菌群结构的研究  

Liver injuries and alterations of gut microbiota in intrahepatic cholestasis in pregnancy of rats

作　　者：何刘媛[1] 张彬[1] 张和平[1] 沈继龙[2] 徐元宏[2] 沈续航 He Liuyuan;Zhang Bin;Zhang Heping;Shen Jilong;Xu Yuanhong;Shen Xuhang(Dept of Laboratory Diagnostics,Maternal and Child Medical Center of Anhui(Anhui Medical University),Hefei 230001;Dept of Laboratory Diagnostics,The First Hospital of Anhui Medical University,Key Laboratory of Pathogenic Biology of Anhui Province,Hefei 230022;Dept of Gastroenterology,The First Hospital of Anhui Medical University,Hefei 230022)

机构地区：[1]安徽省妇幼保健院(安徽医科大学妇幼医学中心)检验科,合肥230001 [2]安徽医科大学第一附属医院检验科,安徽省病原生物学重点实验室,合肥230022 [3]安徽医科大学第一附属医院消化内科,合肥230022

出　　处：《安徽医科大学学报》2023年第5期824-829,共6页Acta Universitatis Medicinalis Anhui

基　　金：病原生物学安徽省重点实验室开放课题(编号:2022013)。

摘　　要：目的探讨妊娠期肝内胆汁淤积症(ICP)大鼠模型肝胆代谢特点及对肠道菌群的影响。方法取孕10 d的SD大鼠40只,随机分为对照组(15只)和ICP组(25只)。妊娠第10~14天给予ICP组大鼠腹腔注射苯甲酸雌二醇(2.5 mg/kg)联合黄体酮(75 mg/kg),构建动物模型,同期对照组给予生理盐水(2.5 ml/kg)腹腔注射。用药后第6天分别检测两组大鼠血清总胆红素(TBIL)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、谷氨酰氨基转移酶(GGT)、碱性磷酸酶(ALP)和总胆汁酸(TBA)水平,比较两组实验大鼠生化指标。取两组大鼠肝脏,病理切片及HE染色,观察ICP大鼠肝脏病理变化。同时收集ICP大鼠新鲜粪便进行16S rDNA测序。结果ICP组大鼠血清TBIL、ALT、AST、GGT、ALP和TBA水平均显著高于对照组(P<0.05)。与对照组比较,ICP组大鼠肝细胞出现显著的脂肪变性,并伴有点状坏死和炎性细胞浸润,部分可见胆栓形成。ICP大鼠肠道菌群出现紊乱,表现为真杆菌、狄氏副拟杆菌、单形拟杆菌等丰度显著下降(P<0.05),而普氏菌和梭杆菌等显著升高(P<0.05)。结论ICP大鼠出现肝组织和肝功能损伤,伴有胆汁酸代谢障碍,并导致母体肠道菌群紊乱。Objective To investigate the effects of hepatobiliary metabolic dysfunction on gut microbiota in rats with intrahepatic cholestasis of pregnancy(ICP).Methods Forty Sprauge-Dawley(SD)rats at 10 days of gestation were randomly divided into two groups,25 for ICP induction and 15 as control.Estradiol benzoate,combined with progesterone,was given to the rats by intraperitoneal injection from 10 to 14 days after gestation.Hepatic impairment indicators of total bilirubin(TBIL),alanine aminotransferase(ALT),aspartate aminotransferase(AST),r-glutamyl transferase(GGT),alkaline phosphatase(ALP),and total bile acids(TBA)in sera of the animals were detected in each group to verify the model construction.Simultaneously,the liver tissues were subjected to pathology examination and fresh faeces samples were collected for 16S rDNA sequencing to explore the gut microbiota profiles.Results The serum levels of TBIL,ALT,AST,GGT,ALP and TBA in ICP group were significantly elevated compared with the control(P<0.05);the ICP rats presented obvious characteristics of hepatobiliary disorders,showing prominent steatosis,necrosis of hepatocytes and infiltration of inflammatory cells,with formation of bile thrombus in some animals.The abundance of Eubacterium,Bacteroides,Parabacteroides distasonis and Bacteroides uniformis remarkably decreased whereas Prevotella and Fusobacterium significantly increased in ICP rats when compared with the control(P<0.05).Conclusion The hepatic injuries and bile acid metabolic disorders occurred in ICP rats,which resulted in dysbiosis of gut microbiota.

关 键 词：妊娠期肝内胆汁淤积症 大鼠模型 肠道菌群 16S rDNA 

分 类 号：R372[医药卫生—病原生物学] R575[医药卫生—基础医学]