VGX-1027对小鼠心脏移植物缺血再灌注损伤的保护作用

The protection of VGX-1027 on myocardial ischemia-reperfusion injury in mice cardiac transplantation

目的:探究VGX-1027对小鼠心脏移植物缺血再灌注损伤的保护作用。方法:取40只C57BL/6小鼠随机分为2组,分别为单纯心脏移植组和心脏移植+VGX-1027治疗组,每组各20只。移植术后24 h获取供心,通过HE染色及CD3、CD4和CD8免疫组织化学观察移植心脏的病理学改变;Western blot法检测移植术后供心caspase-3、Bax和Bcl-2蛋白的表达;ELISA法检测移植术后小鼠血清炎性因子TNF-α、IL-1β和IL-6的表达。结果:与单纯心脏移植组相比,心脏移植+VGX-1027治疗组炎症浸润明显减少,免疫组织化学显示CD3^+T细胞、CD4^+T细胞和CD8^+T细胞的浸润数量明显减少;Western blot法检测结果显示Bax和caspase-3的蛋白表达量显著减少(P<0.05),Bcl-2蛋白的表达量显著增加(P<0.05);ELISA法结果显示血清中TNF-α、IL-1β和IL-6的表达水平显著下降(P<0.05)。结论:VGX-1027可以通过抑制移植心脏的凋亡及炎性因子的释放减轻对心脏移植物缺血再灌注的损伤。

Objective： To explore the effect of VGX-1027 on myocardial ischemia-reperfusion（MI/R） injury in mice cardiac transplantation. Methods： Forty mice were randomly divided into 2 groups： cardiac transplantation group and cardiac transplantation＋VGX-1027 group（70 mg/kg）. The grafts were collected at 24 h after cardiac transplantation. Histopathology was observed with haematoxylin-eosin staining. CD3^＋T cell, CD4^＋T cell and CD8^＋T cell infi ltrated into cardiac grafts were detected by immunohistochemistry. Expression of caspase-3, Bax and Bcl-2 were determined with Western blotting, and cytokines expression of TNF-α, IL-1β and IL-6 were measured with ELISA. Results： Compared with cardiac transplantation group, mice treated with VGX-1027 exhibited signifi cantly lower degree of leukocyte and myocyte necrosis. The infi ltration of CD3^＋T cell, CD4^＋T cell and CD8^＋T cell in grafts were reduced with the treatmet of VGX-1027. The expression of caspase-3 and Bax was inhibited in cardiac transplantation＋VGX-1027 group while the expression of Bcl-2 was increased. Furthermore, VGX-1027 pretreatment resulted in a decrease in serum cytokines of TNF-α, IL-1β and IL-6. Conclusion： VGX-1027 can signifi cantly reduce ischemia-reperfusion injury in mice cervical cardiac transplantation model.