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背景:课题组前期研究证实心肌干细胞移植中期(6周)能有效改善心肌梗死大鼠的心电生理稳定性和室颤阈值,但具体的调控机制和通路不明。目的:探讨心肌干细胞改善心肌梗死大鼠心电生理学稳定性和室颤阈值的相关分子调控机制。方法:通过开胸结扎20只SD大鼠左前降支冠状动脉建立心肌梗死模型,并随机分为2组:心肌干细胞组和PBS组,每组10只。造模后2周心肌干细胞组在局部梗死心肌内注射PKH26标记的由PBS悬浮的心肌干细胞,PBS组在梗死心肌内注射等量PBS。细胞移植后6周取外周血及左心室心肌组织检测ANGⅡ/AT1R/TGF-β1/SMAD/Cx43通路相关因子的变化。结果与结论:(1)与PBS组相比,Cx43在心肌干细胞组梗死区、梗死边缘区、非梗死区的表达明显增加(P<0.01);(2)与PBS组相比,ANGⅡ在心肌干细胞组血浆(P<0.05)和左心室各区域(P<0.01)的表达明显减少;(3)与PBS组相比,心肌干细胞组左心室心肌组织不同区域AT1R、TGF-β1、SMAD2、SMAD3表达下降(P<0.01),而SMAD7表达增加(P<0.05);(4)结果表明,心肌干细胞移植改善心肌梗死大鼠的心电生理学稳定性和室颤阈值的机制可能与调控ANGⅡ/AT1R/TGF-β1/SMAD/CX43通路,导致CX43表达增加密切相关。
Background: The previous study confirmed that the mid-term cardiac stem cell transplantation (6 weeks) can effectively improve the myocardial electrophysiological stability and ventricular fibrillation threshold of myocardial infarction rats, but the specific regulatory mechanisms and pathways are unknown. OBJECTIVE: To investigate the molecular mechanism of cardiac stem cells in improving myocardial electrophysiological stability and threshold of ventricular fibrillation in rats with myocardial infarction. Methods: Myocardial infarction model was established by ligating the left anterior descending coronary artery of 20 SD rats through thoracotomy and randomly divided into 2 groups: cardiac stem cell group and PBS group, 10 rats in each group. Two weeks after model establishment, cardiac stem cells were injected with PKH26-labeled cardiomyocytes stem cells infused into infarcted myocardium. PBS group was infused with an equal volume of PBS. The changes of ANGⅡ / AT1R / TGF-β1 / SMAD / Cx43 pathway in peripheral blood and left ventricular myocardium were detected 6 weeks after cell transplantation. RESULTS AND CONCLUSION: (1) Compared with PBS group, the expression of Cx43 in infarction zone, infarct border zone and non-infarct zone in myocardial stem cell group was significantly higher than that in PBS group (P <0.01); (2) Compared with PBS group, (3) Compared with PBS group, the expression of AT1R, TGF-β1, SMAD2, SMAD3 in different regions of left ventricular myocardium in cardiac stem cell group were significantly lower than those in normal group (P <0.05) (P <0.05). (4) The results showed that the mechanism of myocardial stem cell transplantation to improve myocardial electrophysiological stability and ventricular fibrillation threshold in myocardial infarction rats may be related to the regulation of ANGⅡ / AT1R / TGF-β1 / SMAD / CX43 pathway, leading to increased CX43 expression is closely related.