脂肪间充质干细胞移植对心肌梗死后炎症反应及心室重构的影响

Effect of adipose-derived mesenchymal stem cell transplantation on inflammatory response and ventricular remodeling after myocardial infarction

背景:脂肪间充质干细胞的免疫调节作用是否能够用于心肌梗死的治疗,以及发挥这一作用的最佳时机如何,目前研究较少。目的:观察移植的脂肪间充质干细胞对心肌梗死后炎症反应及心室重构的影响,探讨脂肪间充质干细胞治疗心肌梗死的可能机制。方法:酶消化法分离培养大鼠脂肪间充质干细胞,40只大鼠结扎左冠状动脉前降支建立心肌梗死模型后随机数字表法均分为假手术组、对照组(注射HG-DMEM)、心梗后3 h,7 d移植脂肪间充质干细胞组。移植后14 d采用ELISA法检测血浆肿瘤坏死因子α和白细胞介素10的水平,移植后28 d行超声心动图检测左室舒张末期内径、收缩末期内径、射血分数和短轴缩短率。结果与结论:细胞移植后第14天,与对照组相比,3 h移植组和7 d移植组血浆促炎细胞因子肿瘤坏死因子α的水平明显降低(P<0.01),抗炎细胞因子白细胞介素10的水平明显升高(P<0.01);细胞移植后第28天,与对照组比较,脂肪间充质干细胞移植组左室舒张末期内径和收缩末期内径明显减小,心脏缩小,射血分数和短轴缩短率明显提高,心功能改善,且3 h移植组较7 d移植组作用更趋明显。说明心肌梗死早期进行脂肪间充质干细胞移植,能够显著抑制梗死后炎症反应,调节炎症细胞因子网络平衡,延缓心室重构,改善心脏功能。

BACKGROUND：Whether adipose-derived mesenchymal stem cells are able to exert immunomodulatory effects in the treatment of myocardial infarction, as wel as the best time, is less reported. OBJECTIVE：To observe the effect of adipose-derived mesenchymal stem cells on inflammatory reaction and ventricular remodeling after myocardial infarction, and to explore the possible mechanisms of adipose-derived mesenchymal stem cells for the treatment of myocardial infarction. METHODS：Enzyme digestion method was employed to isolate and culture rat adipose-derived mesenchymal stem cells. By ligation of the left anterior descending coronary artery, we established animal models of myocardial infarction in 40 rats. The rats were randomly divided into four groups：sham group, control group （injected high-glucose Dulbecco’s modified Eagle’s medium）, 3-hour transplantation group （transplanted adipose-derived mesenchymal stem cells after 3 hours of myocardial infarction）, 7-day transplantation group （transplanted adipose-derived mesenchymal stem cells after 7 days of myocardial infarction）. After 14 days of operation, the levels of tumor necrosis factor-αand interleukin-10 in the plasma were detected by enzyme linked＆amp;nbsp;immunosorbent assay. After 28 days of operation, the left ventricular end diastolic diameter, left ventricular end systolic diameter, left ventricular ejection fraction and left ventricular fractional shortening were measured by echocardiography. RESULTS AND CONCLUSION：Compared with the control group, in the 3-hour transplantation group and 7-day transplantation group, the levels of tumor necrosis factor-αwere significantly lower （P〈0.01）, and the levels of interleukin-10 were significantly higher （P〈0.01） at postoperative 14 days;the left ventricular end diastolic diameter and left ventricular end systolic diameter in the two transplantation groups were also significantly smal er （P〈0.05）, but left ventricular ejection fraction and left ventricular fractional shortening were significantly elevated （P〈0.05）, which was more apparent in the 3-hour transplantation group than the 7-day transplantation group. Adipose-derived mesenchymal stem cells transplantation in acute phase of myocardial infarction can suppress the inflammatory response, regulate the cytokine network equilibrium, and thus delay ventricular remodeling and improve cardiac function.