自体骨髓干细胞动员治疗心肌梗死

Repair of infarcted myocardium by intramyocardial transplantation of mobilized autologous bone marrow stem cells

目的探讨基因重组人粒细胞集落刺激因子(rhGCSF)动员骨髓干细胞对急性心肌梗死动物模型的治疗作用。方法将60只SD大鼠随机分成对照组和治疗组,结扎冠状动脉左前降支建立大鼠心肌梗死实验模型。治疗组在复制大鼠心肌梗死模型3h后用经生理盐水稀释的rhGCSF(2mg·L-1)皮下注射10μg·kg-1·d-1,共5d;对照组复制大鼠心肌梗死模型3h后皮下注射等量生理盐水,共5d。在复制大鼠心肌梗死模型24、48h和2周后,两组分别先后各取10只大鼠行在体心功能(±dpdtmax)测定,测定完毕后各组随机选取6只大鼠处死行心脏梗死范围的测量,其余大鼠处死取出心脏行HE染色及CD34+免疫组织化学分析。结果结扎冠状动脉左前降支24、48h和2周后治疗组±dpdtmax均高于对照组(P<0.01);治疗组心脏梗死范围低于对照组(P<0.01)。病理检查显示对照组心肌梗死区周围有较多以中性粒细胞为主的炎症细胞浸润,而治疗组大鼠心肌坏死程度较对照组轻,浸润的细胞以CD34+的单个核细胞为主,并可见新生的心肌细胞生长。结论rhGCSF动员自体骨髓干细胞原位移植可修复梗死心肌、减少梗死范围、提高心功能,可用于急性心肌梗死的治疗。

Objective To investigate the effects of recombinant human granulocyte colony stimulating factor （rhG-CSF） mobilized bone marrow stem cells on treatment of acute myocardial infarction in rats. Methods Sixty rats were randomly divided into control group and treatment group. Under sterilization, rats model were made by opening chest and ligating the left anterior descending （LAD） coronary artery. Three hours after LAD ligation, the rates of treatment group were treated with rhG-CSF （ 10μg· kg^-1·d^-1） for 5 days and those of control group were received saline. Heart fuction （ ＋ dp/dtmax ） was quantified from 24 hours to 2 weeks after LAD ligation, then hearts were harvested for histopathological examination and infarcted zone were quantified, lmmunohistochemistry and HE stain were used to detect infiltration of CD34^＋ monocytes and the regeneration of myocytes in the infarction zone. Results The value of ＋ dp/dtmax of treatment group were higher than that of control group（ P 〈 0.01 ）. Compared with control group, treatment group had smaller infarcted zone（ P 〈 0.01 ）after 2 weeks of LAD hgation. Large number of infiltrative monocytes and some regenerative myocytes with positive expression of CD34^＋ were found in the infarct zones of the treatment group, while majority of the infiltrative inflammatory cells in control group were neutrophils and there were no infiltrative cells and myocytes with positive expression of CD34^＋ . Conclusions In situ transplantation of autologous bone marrow stem cells mobilized by G-CSF can repair the infarcted myocardium, reduce infarction size and improve cardiac founction.