骨髓间充质干细胞通过抑制中性粒细胞CXCR2表达减轻肝脏缺血再灌注损伤

Mesenchymal stem cells alleviate hepatic ischemia reperfusion injury via down-regulation of CXCR2 expression on neutrophils

目的探讨骨髓间充质干细胞(MSC)治疗肝脏缺血再灌注损伤的机制。方法采用SD大鼠制作肝脏70%缺血再灌注损伤模型,并予以MSC静脉注射治疗,再灌注12h收集各组大鼠血清和肝组织标本。通过检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平、肝组织HE染色判断肝脏损伤程度及MSC的治疗作用。通过体外中性粒细胞与MSC共培养及中性粒细胞Transwell实验验证MSC发挥治疗作用的机制。结果 MSC可以降低血清转氨酶并减轻肝脏病理改变。MSC在体外可以下调活化的中性粒细胞表面CXCR2的表达,抑制其趋化。干扰MSC中B7H3蛋白的表达会减弱MSC对中性粒细胞趋化的抑制作用。结论 MSC通过B7H3蛋白下调活化中性粒细胞表面CXCR2表达,抑制其趋化,在缺血再灌注损伤过程中发挥保护作用。

Objective To study the protective potential and possible mechanisms of bone marrow mesenchymal stem cells (MSC)in rat model of hepatic ischemia reperfusion injuries.Methods Establish the SD rat model of 70%hepatic ischemia reperfu- sion injuries and MSC was injected intravenous.Serum and liver tissue were collected 12h post repeffusion.Serum level of ALT and AST,pathologic changes observed by HE stain were used to assess the effects of MSC treatment.MSC was co-cuhured with neutrophils in vitro to disclose the mechanisms of MSC therapy.Results MSC treatment significantly improved the pathologic changes of the liver and reduced the serum level of ALT and AST.MSC suppressed the chemotaxis and infiltration ability of neutrophils via down-regulation of the CXCR2 expression.Deletion of B7H3 in MSC impaired the effect on neutrophils.Conclusion MSC protected the liver experienced ischemia repeffusion injuries by down regulating the expression of CXCR2 on neutrophils via B7H3.