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目的研究骨髓间充质干细胞(BMSCs)移植对心肌梗死后心衰家兔核因子-κB(NF-κB)及炎性因子(IL-6、TNF-α、CRP)的影响;探讨BMSCs移植后减轻炎症反应、改善心室重塑的可能机制。方法新西兰白兔随机分为对照组(假手术组)、急性心肌梗死(AMI)后心衰模型组开胸结扎冠状动脉前降支(LAD)、BMSCs移植组。实时定量PCR法检测心肌组织NF-κB、IL-6、TNF-α的mRNA表达及ELISA法检测血清炎性因子IL-6、TNF-α、CRP浓度。结果细胞移植后28 d,与AMI后心衰模型组相比,正常对照组、BMSCs组舒张末期容积(EDD)均明显减低,射血分数(EF)及缩短分数(FS)均明显增高(P<0.05)。手术后7 d,与正常对照组相比,AMI后心衰模型组、BMSCs组的血清IL-6、TNF-α、CRP的浓度均显著增加(P<0.05),但AMI后心衰模型组和BMSCs组之间差异不显著。细胞移植后28 d,BMSCs组血清IL-6、TNF-α、CRP浓度和心肌组织NF-кB、IL-6、TNF-α比AMI后心衰模型组显著降低(P<0.05)。细胞移植后28 d时,EF与炎性因子呈负相关,与心肌NF-κB呈负相关。结论自体BMSCs移植可显著降低心肌梗死后NF-кB表达及降低炎症反应,减轻左室重塑,改善AMI后心功能。
Objective To investigate the effects of bone marrow mesenchymal stem cells (BMSCs) transplantation on the expression of nuclear factor-κB and inflammatory cytokines (IL-6, TNF-α, CRP) in rabbits with heart failure after myocardial infarction Reduce inflammation, improve the possible mechanism of ventricular remodeling. Methods New Zealand white rabbits were randomly divided into control group (sham operation group) and AMI model group. The anterior descending coronary artery (LAD) and BMSCs transplantation group were treated by thoracotomy. The mRNA expressions of NF-κB, IL-6 and TNF-α in myocardial tissue were detected by real-time quantitative PCR and the concentrations of serum inflammatory cytokines IL-6, TNF-α and CRP were detected by ELISA. Results At 28 days after transplantation, the end-diastolic volume (EDD) and the ejection fraction (EF) and shortening fraction (FS) of the normal control group and the BMSCs group were significantly higher than those of the AMI group <0.05). At 7 days after operation, the concentrations of IL-6, TNF-α and CRP in serum of model group and BMSCs were significantly increased (P <0.05) after AMI compared with those of normal control group. However, There was no significant difference between BMSCs group and BMSCs group. The levels of IL-6, TNF-α, CRP and the levels of NF-κB, IL-6 and TNF-α in BMSCs were significantly lower than those in AMI group after 28 days (P <0.05). At 28 days after cell transplantation, EF was negatively correlated with inflammatory cytokines and negatively correlated with NF-κB. Conclusion Autologous transplantation of BMSCs can significantly reduce the expression of NF-κB and reduce the inflammatory response after myocardial infarction, relieve left ventricular remodeling and improve cardiac function after AMI.