骨髓间充质干细胞对小鼠肝缺血-再灌注损伤修复作用的机制探讨  

Mechanism of bone marrow mesenchymal stem cells in hepatic ischemia-reperfusion injury in mice

作　　者：白云 BAI Yun(The 980th Hospital of PLA Joint Logistical Support Force,Hebei,Shijiazhuang 050082,China)

机构地区：[1]中国人民解放军联勤保障部队第九八〇医院,石家庄市050082

出　　处：《河北医药》2024年第13期1930-1935,共6页Hebei Medical Journal

摘　　要：目的探讨骨髓间充质干细胞(BMSC)对小鼠肝缺血-再灌注损伤过程中淋巴细胞亚群以及细胞多因子表达的影响。方法18只6~8周龄雄性小鼠随机分为假手术组(sham组)、肝脏缺血-再灌注损伤组(HIRI组)和BMSCs干预组(BMSC组),每组6只。检测3组小鼠肝功能及病理学改变;检测3组小鼠肝组织细胞凋亡情况;检测3组小鼠外周血CD4^(+)T细胞、NK细胞及血清中9项细胞多因子白介素-2(IL-2)、IL-4、IL-5、IL-6、IL-10、IL-12、IL-17、肿瘤坏死因子-α(NF-α)、γ干扰素(IFN-γ)的表达水平。结果对照组小鼠肝组织结构正常,HIRI组肝组织结构损伤严重,BMSC组损伤较轻。与HIRI组比较,BMSC组小鼠肝组织损伤学评分较低(P<0.05)。与sham组比较,HIRI组小鼠外周血肝功能指标丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平升高(P<0.05),BMSC组肝功能指标水平差异无统计学意义(P>0.05)。HIRI组肝组织凋亡细胞数量多于BMSC组和Sham组(P<0.05)。与HIRI组比较,BMSC组小鼠外周血中淋巴细胞亚群CD4^(+)T淋巴细胞、NK细胞表达明显下降(P<0.05);已检测的9项细胞多因子中,与HIRI组比较,BMSC组外周血清中IL-4、IL-5、IL-12、IL-17的表达水平升高(P<0.05),TNF-α、IFN-γ的表达水平降低(P<0.05),IL-2、IL-6、IL-10的表达水平差异无统计学意义(P>0.05)。结论在BMSC对小鼠肝缺血-再灌注损伤后的修复过程中,BMSCs可以改善肝功能,抑制细胞凋亡,并通过抑制淋巴细胞(CD4^(+)T淋巴细胞、NK细胞)的表达,并进一步协同调控细胞释放的细胞因子,降低促炎因子,增高抑炎因子,维持HIRI环境中细胞因子稳态。Objective This study aims to investigate the effects of bone marrow mesenchymal stem cells(BMSCs)on lymphocyte subsets and cytokine expressions in mice with hepatic ischemia-reperfusion injury(HIRI).Methods A total of 18 mice with 6-8 weeks old were randomly divided into sham operation group(sham group),HIRI group,and BMSCs intervention group(BMSC group),with 6 mice in each group.Changes in liver function and pathology,as well as the apoptosis of liver cells were evaluated in each group.Additionally,the levels of CD4^(+)T cells,natural killer(NK)cells in peripheral blood,and nine cytokines(interleukin-2[IL-2],IL-4,IL-5,IL-6,IL-10,IL-12,IL-17,tumour necrosis factor alpha[TNF-α],and interferon-gamma[IFN-γ])in serum were measured for each group.Results Mice in the sham group had a normal liver structure,while those in HIRI group had severely damaged liver structure.Mice in BMSC group had a milder damage in the liver.The histological score for liver tissue damage was significantly lower in the BMSC group compared to the HIRI group(P<0.05).The levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in peripheral blood increased in the HIRI group compared to those of the sham group(P<0.05),but they were comparable between BMSC group and HIRI group.The number of apoptotic cells in liver tissues was significantly higher in the HIRI group compared to that of the BMSC group and the sham group(P<0.05).Moreover,the levels of CD4^(+)T cells and NK cells in peripheral blood were significantly lower in the BMSC group compared to those of the HIRI group(P<0.05).However,the levels of IL-2,IL-6,and IL-10 showed no significant differences between HIRI group and BMSC group.Among the nine cytokines detected,serum levels of IL-4,IL-5,IL-12 and IL-17 significantly increased,while the levels of TNF-αand IFN-γdecreased in the BMSC group compared to those of the HIRI group(P<0.05).Conclusion Transplantation of BMSCs in the process of repairing hepatic ischemia-reperfusion injury improves liver function,reduces cell a

关 键 词：骨髓间充质干细胞 肝功能 病理学改变 肝脏缺血-再灌注损伤 

分 类 号：R329.447[医药卫生—人体解剖和组织胚胎学]