压力负荷大鼠心肌重构与TNF-α和IL-10表达的动态相关性研究

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目的:动态观察压力负荷增高致大鼠心肌重构发生发展过程中TNF-α和IL-10在心肌组织中表达的变化,并探讨其与左心室质量指数(LVMI)和心肌胶原纤维容积分数(CVF)的动态相关关系。方法:大鼠随机分为对照组、假手术组和模型组。腹主动脉缩窄法复制压力负荷增高致大鼠心肌重构的动物模型,模型组进一步分为术后2周、4周、8周和12周组;双抗体夹心ABC-ELISA法,动态检测心肌组织内TNF-α和IL-10表达的变化;改良Mallory氏三色染色检测心肌组织内胶原纤维含量的动态变化。结果:术后4周心肌细胞呈进行性排列紊乱、肌丝断裂,细胞间隙明显增宽,可见大量异常胶原纤维堆积,并在术后12周出现明显的心衰;ELISA检测结果提示,4周、8周和12周组心肌组织TNF-α表达呈时间依赖性升高,与对照组比较,具有显著统计学差异(P<0.01);心肌组织TNF-α表达量与LVMI(r=0.582,P<0.01)和CVF(r=0.932,P<0.01)均呈显著正相关;IL-10在各组心肌组织中的表达无统计学差异,但TNF-α与IL-10比值在术后呈时间依赖性升高,由(1.79±0.19)ng/mL(2周)上升到(2.85±0.24)ng/mL(12周),与对照组(1.74±0.24)ng/mL比较,差异具有统计学意义(P<0.01)。结论:心肌重构的程度呈时间依赖性加剧是心功能恶化的关键因素,TNF-α在心肌组织表达的时间依赖性上调和TNF-α与IL-10比例失调是可能是心肌重构的重要分子机制之一。 OBJECTIVE: To dynamically observe the changes of TNF-α and IL-10 in myocardium during the development of myocardial remodeling induced by pressure overload in rats, and to investigate the correlation between the expression of TNF-α and IL-10 in myocardium, CVF) dynamic correlation. Methods: The rats were randomly divided into control group, sham operation group and model group. The model group was further divided into 2 weeks, 4 weeks, 8 weeks and 12 weeks after the abdominal aorta stenosis. The model group was further divided into two groups: ABC-ELISA with double antibody sandwich method and dynamic detection The changes of TNF-α and IL-10 expression in myocardial tissue were observed. The changes of collagen fibers in myocardial tissue were detected by modified Mallory’s trichrome staining. Results: Cardiomyocytes were disordered, the myofilaments were broken and the intercellular space was obviously enlarged 4 weeks after operation. A large number of abnormal collagen fibers accumulated and showed obvious heart failure 12 weeks after operation. (P <0.01). The expression of TNF-α in myocardial tissue was positively correlated with LVMI (r = 0.582, P <0.01) and CVF (r = 0.932, P <0.01). There was no significant difference in the expression of IL-10 in each group, but the ratio of TNF-α and IL-10 in postoperative Compared with the control group (1.74 ± 0.24) ng / mL, the difference was statistically significant from (1.79 ± 0.19) ng / mL (2 weeks) to (2.85 ± 0.24) ng / mL Significance (P <0.01). Conclusion: The time-dependent increase of myocardial remodeling is the key factor of cardiac dysfunction. The time-dependent up-regulation of TNF-α expression in myocardium and the imbalance of TNF-α and IL-10 may be important for myocardial remodeling. One of the molecular mechanisms.
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