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间充质干细胞预处理对肝脏缺血再灌注损伤的保护作用
作者:王珣1  王帅2  施晓雷1 
单位:1. 南京大学医学院附属鼓楼医院 肝胆外科, 江苏 南京 210008;
2. 南京医科大学鼓楼临床学院 肝胆外科, 江苏 南京 210008
关键词:间充质干细胞 HO-1 中性粒细胞 缺血再灌注损伤 
分类号:R459.9
出版年·卷·期(页码):2017·36·第五期(716-720)
摘要:

目的:探讨间充质干细胞(MSCs)对大鼠肝脏缺血再灌注损伤的保护作用及其相关机制。方法:36只健康Wistar大鼠随机分为三组(每组12只),对照组、缺血再灌注组(IR组)和间充质干细胞治疗组(MSCs组)。各组分别于再灌注6 h后留取大鼠外周血及肝脏组织,检测血清中ALT,AST水平,肝脏组织行HE染色法观察损伤情况,免疫组化鉴定髓过氧化物酶(MPO)阳性细胞,western blot检测Bcl,HO-1表达水平。结果:再灌注6 h后,与对照组相比,IR组血清中ALT,AST水平升高,肝组织内Bcl表达下降,HO-1有所上升,MPO阳性细胞增多,差异有统计学意义(P < 0.05),肝脏组织HE切片显示肝细胞肿胀,局部肝细胞坏死。与IR组相比,MSCs组血清ALT,AST水平下降,肝细胞肿胀程度减轻,坏死区域减少,组织内Bcl表达有所恢复,差异均存在统计学差异(P < 0.05)。此外,MSCs组肝脏HO-1表达上升,中性粒细胞募集减少。结论:MSCs可能通过提高肝脏内HO-1表达水平以及减少中性粒细胞募集缓解大鼠肝脏缺血再灌注损伤。

Objective: To investigate the protective effects of mesenchymal stem cells(MSCs) on rats hepatic ischemia reperfusion injury model. Methods: Thirty-six rats were randomly divided into three groups:control group, IR group, MSCs group. Control group underwent anesthesia followed with the isolation of portal vein without blood flow occlusion. The ischemia reperfusion injury model was conducted by clamping portal triad to interrupt the blood supply. The blood and liver were collected after 6 h reperfusion. MSCs group was conducted by pretreatment with 1×106 MSCs 30 mins before ischemia. The level of ALT, AST and liver histopathology sections were compared. Western blot were used to measure the expression of Bcl and HO-1. Immunohistochemisty was conducted to measure MPO-positive cells to reflect the neutrophil recruitment. Results: Ischemia reperfusion injury model was successfully conducted. Compared with control group, the levels of ALT and AST increased in IR group,the liver section was marked abnormalities and Bcl was decreased. Compared with IR group, it showed lower level of ALT, AST, less damage area and increased Bcl in MSCs group. In addition, livers from the MSCs group showed reduced neutrophil recruitment. Conclusion: This study revealed that MSCs protected against liver I/R injury via promoting HO-1 expression and reducing the recruitment of neutrophils.

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