间充质干细胞联合免疫抑制剂对肝移植大鼠模型免疫排斥的影响  

Effect of mesenchymal stem cells combined with immunosuppressants on immune rejection in a rat model of liver transplantation

作　　者：李海涛 俞赛花 陈丽红 赖子森 刘海岩 刘红枝 沈聪龙 LI Haitao;YU Saihua;CHEN Lihong;LAI Zisen;LIU Haiyan;LIU Hongzhi;SHEN Conglong(Department of Minimally Invasive Hepatopancreatobiliary Surgery,Mengchao Hepatobiliary Hospital of Fujian Medical University,Fuzhou 350011,China;Department of Pathology,Mengchao Hepatobiliary Hospital of Fujian Medical University,Fuzhou 350011,China;College of Biological Science and Engineering,Fuzhou University,Fuzhou 350116,China)

机构地区：[1]福建医科大学孟超肝胆医院肝胆胰脾微创外科,福州350011 [2]福建医科大学孟超肝胆医院病理科,福州350011 [3]福州大学生物科学与工程学院,福州350116

出　　处：《临床肝胆病杂志》2024年第6期1209-1214,共6页Journal of Clinical Hepatology

基　　金：福建省自然科学基金(2020J011163);福建省卫生健康委医学创新项目(2020CXA054);福州市临床重点专科建设项目(20230101)。

摘　　要：目的探讨间充质干细胞(MSC)联合免疫抑制剂(IS)对肝移植大鼠模型免疫排斥反应的影响。方法将F344大鼠分成5组:Normal组(不进行任何干预)、PS组(注射等量生理盐水)、MSC组(注射MSC)、IS组(注射IS)、MSC+IS组(注射MSC和IS),每组8只。除Normal组以外,各组均采用Kamada双袖套法不重建肝动脉建立原位肝移植模型。大鼠肝组织进行HE染色、Masson染色并进行纤维化程度统计,免疫组化实验检测T淋巴细胞和NK细胞浸润情况,免疫荧光实验分析巨噬细胞M2极化情况。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。Kaplan-Meier法绘制生存曲线,生存分析采用Log-rank检验。结果与PS组相比,MSC+IS组生存期显著延长(P<0.01),MSC组、IS组和MSC+IS组的肝组织结构明显改善,纤维化程度显著降低(P值均<0.0001),NK细胞和T淋巴细胞浸润数量显著减少(P值均<0.0001),巨噬细胞M2极化程度显著增加(P值均<0.0001),提示MSC+IS组的疗效显著优于MSC组和IS组。结论MSC联合IS可以改善大鼠肝移植术后肝组织病理,降低炎性细胞浸润,促进巨噬细胞M2极化,起免疫抑制作用。Objective To investigate the effect of mesenchymal stem cells(MSCs)combined with immunosuppressants(IS)on immune rejection in a rat model of liver transplantation.Methods F344 rats were divided into Normal group(without any intervention),PS group(injected with an equal volume of normal saline),MSC group(injected with MSC),IS group(injected with IS),and MSC+IS group(injected with MSC and IS),with 8 rats in each group.For all rats except those in the Normal group,the Kamada’s double-cuff method was used to establish a model of orthotopic liver transplantation,without reconstruction of the hepatic artery.HE staining and Masson staining were performed for rat liver tissue,and the degree of liver fibrosis was analyzed;immunohistochemical experiments were used to measure the infiltration of T cells and NK cells,and immunofluorescence assay was used to analyze macrophage M2 polarization.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.The Kaplan-Meier method was used to plot survival curves,and the log-rank test was used for survival analysis.Results Compared with the PS group,the MSC+IS group had a significantly prolonged survival time(P<0.01),and the MSC group,the IS group,and the MSC+IS group had a significant improvement in the histological structure of the liver and a significant reduction in the degree of liver fibrosis(all P<0.0001),as well as a significant reduction in the infiltration of NK and T cells(all P<0.0001)and a significant increase in the degree of macrophage M2 polarization(all P<0.0001).The MSC+IS group had a significantly better effect than the MSC group and the IS group.Conclusion MSCs combined with IS can improve liver histopathology,reduce inflammatory cell infiltration,promote macrophage M2 polarization,and exert an immunosuppressive effect in rats after liver transplantation.

关 键 词：肝移植 间质干细胞 移植物排斥 

分 类 号：R657.3[医药卫生—外科学] R-332[医药卫生—临床医学]