单独或联合应用rhG-CSF与bFGF对大鼠急性心肌梗塞的治疗作用

Effects of using rhG-CSF and bFGF alone or combined on acute myocardial infarction in rats

目的:研究重组人粒细胞集落刺激因子(rhG-CSF)与碱性成纤维细胞生长因子(bFGF)单独或联合腹腔注射对大鼠急性心肌梗塞(AMI)的治疗作用。方法:结扎大鼠冠状动脉前降支制作AMI模型。成活大鼠随机分为4组:心梗对照组(MI)、rhG-CSF组(G)、bFGF组(B)和联合治疗组(GB),造模后24h开始依次分别腹腔注射生理盐水、rhG-CSF、bFGF和rhG-CSF+bFGF。另设假手术组(S),只开胸不造模,不给药。分别计数注射前和注射后1周大鼠外周血白细胞(WBC)和单个核细胞(MNC)百分比,心梗后1周免疫组化染色观察CD34+细胞表达,HE染色计数新生毛细血管,心梗后4周HE染色观察心肌病理改变,计数毛细血管,测量心功能和梗塞面积。结果:G、B、GB组与MI组比较,及GB组与G组或B组相比,外周血WBC计数、MNC百分比、梗塞区周围CD34+细胞计数、毛细血管密度升高(P<0.01),梗塞面积减小(P<0.01),+dp/dtmax、-dp/dtmax和LVSP增高(P<0.01),LVDP降低(P<0.01)。结论:腹腔注射rhG-CSF可以动员大量心肌样细胞;腹腔注射rhG-CSF或bFGF都可以促进血管侧支循环建立,增加梗塞区毛细血管数量,两者都可缩小梗塞面积,改善心脏的收缩功能;联合应用较单独应用效果更佳。

Objective To study the effects of injecting recombinant human granulocyte colony stimulating factor （rhG-CSF） and basic fibroblast growth factor （bFGF） alone or combined on actue myocardial infarction （AMI）. Methods AMI models were induced by ligation of the left anterior descending artery. The survived rats were divided into four groups randomly： AMI group （MI）, rhG-CSF group （G）, bFGF group （13）, combined group （GB）. Respectively, saline, rhG-CSF, bFGF, and rhG-CSF plus bFGF were injected intraperitoneally 24 h after AMI. Also, sham-operated group （S） was established with only chest-opeaned, without ligation, and no drugs intervention. The white blood cells （WBC） and mononuclear cells （MNC） proportion in peripheral blood were counted 1 week before and 1 week after the intervention, and the number of CD34＋ cells was observed with immunohistochemical staining 1 week after AMI in order to compare the situation of mobilization in peripheral blood; the capillary density was evaluated by HE staining both 1 and 4 weeks after AMI; their cardiac ruction was determined in vivo, the infarction size in each group was calculated, and the pathological changes in rat myocardium were observed by HE staining 4 weeks after AMI. Results Compared with MI group, the number of WBC and MNC% in peripheral blood 1 week after AMI in G, B and GB groups were higher （P〈0. 01） ; LVSP,＋dp/dtmax and --dp/dtmax in vivo in G, B and GB groups increased further （P〈0.01） and LVDP decreased lower （P〈0.01）. Conclusion Injecting rhG-GSF intraperitoneally can mobilize bone marrow stera cells into peripheral blood in infarct rats. The mobilized stem cells may enter into the infarct area and induce the regeneration of cardiaclike cells and capillary endothelial cells. Injecting rhG-GSF or bFGF intraperitoneally may also promote the regeneration of capillary in infarct area. Both of them can improve the cardiac function significantly, rhG-GSF combined with bFGF would be better than use alone.