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骨髓间充质干细胞移植对大鼠梗死心脏核因子кB活性的影响
Inhibition of Nuclear Factor-κB Activity by Mesenchymal Stem Cells in Rats with Myocardial Infarction
【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。
【Abstract】 Objective To investigate the effect of mesenchymal stem cells (MSC) on the activity of nuclear factor (NF)-κB 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 allo- cated into three groups randomly:1)sham group (without ligation of the artery,n=8);2)injection of PBS solu- tion (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 u- sing physiological recorder.Western blot were performed to investigate the nuclear factor-α activity.The ex- pressions 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 inhibi- ted the activities of NF-κB 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 at- tribute to their immuno-inflammatory regulation mechanism.
【Key words】 Mesenchymal stem cells; Myocardial infarction; Inflammatory response;
- 【文献出处】 中华高血压杂志 ,Chinese Journal of Hypertension , 编辑部邮箱 ,2008年06期
- 【分类号】R542.22
- 【被引频次】6
- 【下载频次】174