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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

李海涛 俞赛花 陈丽红 赖子森 刘海岩 刘红枝 沈聪龙

引用本文:
Citation:

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

DOI: 10.12449/JCH240622
基金项目: 

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)

伦理学声明: 本研究方案于2023年5月25日经由福建医科大学孟超肝胆医院实验动物伦理委员会审批,批号:MCHH-AEC-2023-04,符合实验室动物管理与使用准则。
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:李海涛负责设计论文框架,起草论文;俞赛花、刘海岩负责实验操作,研究过程的实施;陈丽红、赖子森、刘红枝、沈聪龙负责数据收集,统计学分析。
详细信息
    通信作者:

    李海涛, lht45182@163.com (ORCID: 0000-0003-4680-4752)

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

Research funding: 

The Natural Science Foundation of Fujian Province (2020J011163);

The Medical Innovation Project of Fujian Province (2020CXA054);

Key Clinical Specialty Discipline Construction Program of Fuzhou (20230101)

More Information
    Corresponding author: LI Haitao, lht45182@163.com (ORCID: 0000-0003-4680-4752)
  • 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<0.000 1),NK细胞和T淋巴细胞浸润数量显著减少(P值均<0.000 1),巨噬细胞M2极化程度显著增加(P值均<0.000 1),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。

     

  • 图  1  MSC的外形鉴定(×20)

    Figure  1.  Shape identification of MSC(×20)

    图  2  MSC的表型鉴定

    Figure  2.  Phenotypic identification of MSC

    图  3  大鼠肝移植后Kaplan-Meier生存曲线

    Figure  3.  Kaplan-Meier survival curve after liver transplantation in rats

    图  4  各组大鼠肝组织病理切片

    Figure  4.  Histopathological sections of rat liver in various groups

    图  5  大鼠肝移植术后肝组织纤维化程度统计图

    Figure  5.  Statistical graph of the degree of fibrosis in liver tissue after liver transplantation in rats

    图  6  各组大鼠肝组织CD56、CD3指标免疫组化染色

    注: a,免疫组化染色(×40);b、c,CD56、CD3阳性细胞占比统计结果。

    Figure  6.  Immunohistochemical staining of rat liver tissue for CD56 and CD3 indicators in each group

    图  7  各组大鼠肝组织免疫荧光染色

    注: DAPI、CD68、CD163与Merge放大倍数为20,Enlarge放大倍数为63。

    Figure  7.  Immunofluorescence staining of rat liver tissue in each group

    图  8  各组大鼠肝组织巨噬细胞M2型极化占比统计图

    Figure  8.  Statistics of the percentage of macrophage M2 type polarisation in liver tissue of rats in each group

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  • 收稿日期:  2023-10-10
  • 录用日期:  2023-11-08
  • 出版日期:  2024-06-25
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