肝祖细胞移植减轻小鼠胆汁淤积性肝纤维化及其肝损伤程度  

Transplantation of hepatic progenitor cells alleviates cholestatic liver fibrosis and liver injury in mice

作　　者：马振增[1] 顾林[1] 赵睿[1] 邓敏[1] 朱玉[1] 王启之[1] 柯希权 汪建超[1] 燕善军[1] Ma Zhenzeng;Gu Lin;Zhao Rui;Deng Min;Zhu Yu;Wang Qizhi;Ke Xiquan;Wang Jianchao;Yan Shanjun(Department of gastroenterology,the first affiliated hospital of Bengbu Medical College,Bengbu,Anhui,233004,China)

机构地区：[1]蚌埠医学院第一附属医院消化内科,安徽蚌埠233004

出　　处：《齐齐哈尔医学院学报》2022年第12期1101-1105,共5页Journal of Qiqihar Medical University

基　　金：安徽省教育厅重点项目(KJ2019A0369)。

摘　　要：目的 研究肝祖细胞(hepatic progenitor cell, HPC)移植对胆汁淤积性肝纤维化及其肝损伤的治疗效果。方法 雄性野生型C57BL/6小鼠随机分为正常饮食组(对照组),3,5-diethoxycarbonyl-1,4-dihydrocollidine(DDC)饮食组及HPC移植组三组,每组各15只。DDC饮食喂养小鼠6周以诱导胆汁淤积性肝损伤及其肝纤维化模型,HE染色观察肝脏损伤程度,CK19免疫组化观察胆管反应,两部灌注法分离HPC,AFP、ALB及CK19免疫荧光染色鉴定HPC,Masson染色观察肝纤维化程度,α-SMA免疫组化观察星状细胞活性,ELISA检测小鼠血清IL-6、ALT、AST及TBIL浓度。结果 与对照组比较,DDC组胆管反应明显增加(P<0.05)。HPC高表达AFP和CK19,不表达ALB。与对照组和DDC组比较,移植HPC组胆管反应较DDC组减弱,但比对照组增强(P<0.05);移植HPC组肝纤维化及星状细胞活性比DDC组明显减弱,但高于对照组(P<0.05);与Control组比较,DDC组及HPC移植组IL-6、ALT、AST及TBIL水平显著升高(P<0.05);与DDC组比较,HPC移植组肝细胞损伤标志物(IL-6、ALT、AST及TBIL)水平显著下降(P<0.05)。结论 HPC移植治疗可以显著减轻小鼠胆汁淤积性肝病模型的肝脏损伤及其纤维化程度。Objective To study the therapeutic effect of hepatic progenitor cell(HPC) transplantation on cholestatic liver fibrosis and its liver injury.Methods Male wild-type C57 BL/6 mice were randomly divided into normal diet group(control group), 3,5-diethoxycarbonyl-1,4-dihydrocollidine(DDC) diet and HPC transplantation group, with 15 mice in each group. The mice were fed with DDC diet for 6 weeks to induce cholestatic liver injury and its liver fibrosis model. HE staining was used to observe the degree of liver injury;CK19 immunohistochemistry was used to observe bile duct reaction;HPCs were isolated by two-part perfusion method. Immunofluorescence of AFP and ALB and CK19 were used to identify HPCs, and Masson staining was used to observe the degree of liver fibrosis. The activity of hepatic stellate cells was observed by α-SMA immunohistochemistry, and then the concentrations of IL-6, ALT, AST and TBIL in serum were detected by ELISA. Results Compared with the control group, bile duct reaction in DDC group was significantly increased(P<0.05). AFP and CK19 were highly expressed in hepatic progenitor cells, but ALB was not. Compared with the control and the DDC group, the bile duct reaction in the transplantation group was weaker than that in the DDC group, but stronger than that in the control group(P<0.05). The activity of hepatic stellate cells and the degree of liver fibrosis in the transplantation group was significantly lower than that in the DDC group, but higher than that in the control group(P<0.05). Compared with control group, the levels of liver injury makers(IL-6, ALT, AST and TBIL) in DDC and HPC transplantation group were significantly increased(P<0.05). However, compared with DDC group, the levels of IL-6, ALT, AST and TBIL in HPC transplantation group were significantly decreased(P<0.05).Conclusions HPC transplantation could significantly reduce the degree of liver injury and fibrosis in mice with cholestatic liver injury and fibrosis.

关 键 词：胆汁淤积性肝损伤 胆汁淤积性肝纤维化 肝祖细胞 移植 小鼠 

分 类 号：R575.2[医药卫生—消化系统]