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背景:前期研究发现骨髓间充质干细胞移植能够改善心肌梗死大鼠的心功能,但整体效果并不太理想。目的:拟采用PPAR-γ激动剂吡格列酮联合骨髓间充质干细胞移植治疗以进一步改善心肌梗死大鼠的心功能并探讨相关机制。方法:开胸结扎20只SD大鼠左前降支冠状动脉并随机分为2组:骨髓间充质干细胞组和骨髓间充质干细胞+吡格列酮组。2周后在局部梗死心肌内注射PKH26标记的由PBS悬浮的骨髓间充质干细胞,联合治疗组在注射骨髓间充质干细胞后予以吡格列酮3 mg/(kg·d)连续灌胃2周。细胞移植后2周进行超声心动图检测,免疫荧光染色、Western blot、q RT-PCR检测左心室心肌组织不同区域PPAR-γ、TGF-β1/SMAD通路相关因子和Cx43的表达情况。结果与结论:两组大鼠基础心功能参数无明显差异性。细胞移植2周后,骨髓间充质干细胞+吡格列酮组左室舒张末径、左室收缩末径明显减小,左室射血分数明显增高;左心室心肌组织不同区域PPAR-γ和Cx43的表达量显著增加;TGF-β1、SMAD2、SMAD3在梗死区和梗死边缘区表达明显下降。以上结果提示PPAR-γ激动剂吡格列酮干预能够增强骨髓间充质干细胞移植对心功能的改善作用,其机制可能与PPAR-γ抑制TGF-β1/SMAD通路进而提高Cx43的表达有关。
Background: Previous studies found that bone marrow mesenchymal stem cell transplantation can improve cardiac function in myocardial infarction rats, but the overall effect is not very satisfactory. OBJECTIVE: To explore the possible mechanism of cardiac function in myocardial infarction rats by using PPAR-γ agonist pioglitazone and bone marrow mesenchymal stem cell transplantation. Methods: Thoracotomy was performed on the left anterior descending coronary artery in 20 SD rats and randomly divided into 2 groups: BMSCs group and BMSCs + Pioglitazone group. Two weeks later, PKH26-labeled MSCs suspended in PBS were injected into the infarcted myocardium. The combined treatment group was given pioglitazone 3 mg / (kg · d) for 2 weeks after the injection of bone marrow mesenchymal stem cells. The expression of PPAR-γ, TGF-β1 / SMAD pathway related factors and Cx43 in different regions of left ventricular myocardium were detected by immunofluorescent staining, Western blot and q RT-PCR two weeks after cell transplantation. RESULTS AND CONCLUSION: There was no significant difference in basic cardiac function parameters between the two groups. After 2 weeks of transplantation, left ventricular diastolic diameter, left ventricular end-diastolic diameter and left ventricular ejection fraction were significantly increased in BMSCs + pioglitazone group. Expression of PPAR-γ and Cx43 in different regions of left ventricular myocardium The levels of TGF-β1, SMAD2 and SMAD3 were significantly decreased in infarct area and infarct border area. The above results suggest that PPAR-γ agonist pioglitazone can enhance the cardiac function of bone marrow-derived mesenchymal stem cells transplantation. The mechanism may be related to the inhibition of TGF-β1 / SMAD pathway and the expression of Cx43 by PPAR-γ.