重组人肝细胞生长因子对心脏移植后冠状动脉内膜c-Met表达的影响

Effects of Human Recombinant Hepatocyte Growth Factor on the Expression of c-Met in Intima of Allograft Coronary Arteries after Heart Transplantation

目的探讨重组人肝细胞生长因子(rh-HGF)对大鼠移植心脏冠状动脉内膜c-Met表达的影响及其意义。方法雄性Wistar大鼠80只,雄性SD大鼠40只,建立腹腔异位心脏移植模型。将60只受体大鼠分为3组,对照组:20只Wistar大鼠,术后当天开始腹腔注射生理盐水1ml/kg.d;环孢菌素A(CsA)组:20只SD大鼠,术后当天开始腹腔注射CsA5mg/kg.d;rh-HGF组:20只SD大鼠,术后当天开始腹腔注射rh-HGF500μg/kg.d+CsA5mg/kg.d。分别于术后15d、60d观察冠状动脉的病理变化;采用免疫组织化学方法检测冠状动脉内膜c-Met的表达,逆转录聚合酶链反应(RT-PCR)检测冠状动脉内膜c-MetmRNA的表达。结果rh-HGF组移植心脏冠状动脉内皮细胞完整,内膜轻度增厚,管腔轻度狭窄,病理改变明显轻于CsA组。术后15d、60drh-HGF组c-Met和c-MetmRNA在移植心脏冠状动脉内膜的表达均明显高于CsA组和对照组(术后60dc-Met:1.85±0.26vs.0.96±0.10,t=8.491,P=0.000;1.85±0.26vs.0.58±0.03,t=13.725,P=0.000;术后60dc-MetmRNA:1.92±0.22vs.0.88±0.07,t=11.940,P=0.000;1.92±0.22vs.0.42±0.02,t=19.206,P=0.000)。结论rh-HGF通过上调移植心脏冠状动脉内膜c-Met的表达,可促进冠状动脉内皮细胞修复和再生,预防移植心脏血管病的发生。

Objective To investigate the effects of human recombinant hepatocyte growth factor （rh-HGF） on the expression of c-Met in intima of allograft vessels after cardiac transplantation in rats. Methods Heterotopic heart transplantation were established in abdominal cavity with eighty Wistar rats and forty SD rats. Donors＇ cardiac grafts from Wistar rats were transplanted to SD rats （allograft） or Wistar rats （isograft）. Sixty recipient rats were divided into three groups, control group：20 Wistar rats were injected with normal saline 1ml/kg · d intraperitoneally after transplantation; cyclosporine A （CsA） group： 20 SD rats were injected with CsA 5mg/kg · d intraperitoneally on operation day; rh-HGF group： 20 SD rats were injected with rh-HGF 500μg/kg · d and CsA 5mg/kg · d intraperitoneally on operation day. The cardiac grafts were harvested at the 15th clay and 60th clay after transplantation. The cross-section of vascular tissues were used for immunohistochemistrical staining of c-Met, and investigated the expression of c-Met messenger ribonucleic acid （mRNA） in intima of allograft vessels by reverse transcription-polymerase chain reaction （RT-PCR）. The pathologic changes of allograft coronary vessels were observed with histopathological method. Results The allograft coronary arteries showed minimal intimal thickening, the endothelium and internal elastic lamina remained almost intact in rh-HGF group after transplantation. The expression of c-Met and c-Met mRNA in intima of allograft vessels after transplantation in rh-HGF group were significantly higher than those in CsA group and control group（expression of c-Met at 60d： 1.85±0.26 vs. 0.96±0.10, t=8. 491,P=0.000;1.85±0.26 vs. 0.58±0.03, t=13.725,P=0.000; expression of c-Met mRNAat 60d： 1.92±0.22 vs. 0. 88±0. 07, t=11. 940,P=0. 000;1. 92±0. 22 vs. 0. 42±0. 02, t=19. 206,P=0. 000）. Conclusion rh-HGF may prevent the progression of cardiac allograft vasculopathy through upregulating the expression of c-Met to stimulate endothelial cell repair and growth.