摘要
目的观察骨髓间充质干细胞对心肌梗死的治疗效果,以及心肌梗死后炎症因子表达的影响,探讨其治疗心肌梗死的可能机制。方法提取 SD 大鼠骨髓间充质干细胞,体外培养、纯化扩增。采用结扎冠状动脉前降支方法复制大鼠心肌梗死模型,将建立的模型随机分为:1)假手术组(仅穿线不结扎血管,n=8);2)PBS 溶液注射组(n=8);3)干细胞移植组(n=8)。模型制作成功即刻,将骨髓间充质干细胞通过心外膜分4点注射到梗死周边部位。4周后测定血流动力学指标。随后通过 Western blot 方法测定核因子 kB 活性,RT-PCR 和 westernblot 法测定肿瘤坏死因子α、白介素6 mRNA 和蛋白表达。结果 1)4周后,假手术组大鼠死亡率20%(2/10),治疗阴性对照组大鼠死亡率33.3%(4/12),干细胞移植组大鼠死亡率20%(2/10),3组死亡率没有统计学差异(P=0.646);2)与注射 PBS 溶液相比,骨髓间充质干细胞移植可以改善心肌梗死大鼠血流动力学指标;3)骨髓间充质干细胞可以抑制大鼠梗死心肌核因子 kB 活性,下调肿瘤坏死因子α和白介素6 mRNA 和蛋白表达水平。结论骨髓间充质干细胞可以改善心肌梗死大鼠的心功能,同时可调节大鼠梗死心脏炎症反应。
Objective To investigate the effect of mesenchymal stem cells (MSC) on the activity of nuclear factor (NF)-kB in rats with myocardial infarction. Methods MSC were isolated from SD rats (120--150 g in weight). SD rats (180--200 g in weight) were subjected to MI by left coronary artery occlusion, and were allocated into three groups randomly: 1)sham group (without ligation of the artery, n=8);2)injection of PBS solution (n=8); 3)injection of MSC (n=8). MSC or PBS solution was injected into myocardium from epicardium instantly after MI models were established. Four weeks after transplantation, cardiac function was evaluated using physiological recorder. Western blot were performed to investigate the nuclear factor-α activity. The expressions of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were evaluated by RT-PCR and Western blot. Results 1)Mortality was 20%(2/10) in sham group, 33.3%(4/12) in PBS group and 20%(2/10) in MSC group with no statistic differences between them(P=0.646). 2)Hemodynamic measurements showed that MSC trans-plantation caused significant improvement in cardiac function, comparing with MI+PBS group. 3) MSC inhibited the activities of NF-kB in myocardium and down-regulated the expression of TNF-α and IL-6 in mRNA and protein level. Conclusion Transplantation of MSC improved cardiac function in MI rats, which may partly attribute to their immuno-inflammatory regulation mechanism.
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2008年第6期551-555,共5页
Chinese Journal of Hypertension
基金
湖南省自然科学基金资助项目(07JJ3044)
关键词
骨髓间充质干细胞
心肌梗死
炎症反应
Mesenchymal stem cells
Myocardial infarction
Inflammatory response