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目的观察肿瘤坏死因子-α(TNF-α)对心力衰竭大鼠连接蛋白(Cx)43表达和分布调控作用,并探讨其与室性心律失常发生的关系。方法 36只SD大鼠随机分为3组,每组12只:心衰组(F组)、加药组(D组)、假手术组(S组)。通过腹主动脉缩窄法构建心力衰竭模型,D组待术后第2周开始应用TNF-α螯合剂rhTNFR:Fc至第16周。术后第16周应用程序刺激诱发室性心律失常,记录各组诱发情况。Western blot检测心肌组织TNF-α、总CX43(T-Cx43)、磷酸化CX43(P-Cx43)和非磷酸化CX43(NP-Cx43)的蛋白表达水平,应用激光共聚焦显微镜观察T-Cx43的分布情况。结果与S组相比,F组心肌组织TNF-α表达显著增加(P<0.05),T-Cx43表达下降且分布紊乱,P-Cx43水平下降且NP-Cx43水平增加(P<0.05),室性心律失常诱发率明显升高(P<0.05);与F组比较,D组TNF-α表达显著减少(P<0.05),T-Cx43和P-Cx43水平有所增加(P<0.05),NP-Cx43水平下降(P<0.05),T-Cx43分布紊乱有所减轻,室性心律失常诱发率显著下降(P<0.05)。结论心力衰竭大鼠心肌组织中过表达的TNF-α可以诱导Cx43重构,其在心衰室性心律失常的发生中可能发挥重要作用。
Objective To observe the regulatory effect of tumor necrosis factor-α (TNF-α) on the expression and distribution of connexin (Cx) 43 in rats with heart failure and to explore its relationship with ventricular arrhythmia. Methods Thirty - six SD rats were randomly divided into 3 groups with 12 rats in each group: heart failure group (F group), dosing group (D group) and sham operation group (S group). The model of heart failure was established by abdominal aortic constriction. Group D received TNF-α chelator rhTNFR: Fc from the second week after operation until the 16th week. Sixteen weeks after application of ventricular arrhythmias induced by stimulation to record the induction of each group. The protein expression of TNF-α, total CX43 (T-Cx43), phosphorylated CX43 (P-Cx43) and non-phosphorylated CX43 (NP-Cx43) in myocardium were detected by Western blotting. The expression of T-Cx43 Distribution. Results Compared with S group, the expression of TNF-α in myocardial tissue of F group was significantly increased (P <0.05), the expression of T-Cx43 was decreased and the distribution was disorganized, the level of P-Cx43 was decreased and the level of NP-Cx43 was increased (P <0.05). Compared with group F, the expression of TNF-α in group D was significantly decreased (P <0.05), and the levels of T-Cx43 and P-Cx43 were increased The level of NP-Cx43 decreased (P <0.05), the distribution of T-Cx43 was reduced, and the induction rate of ventricular arrhythmia was significantly decreased (P <0.05). Conclusion Overexpression of TNF-α in cardiac tissue of heart failure rats can induce Cx43 remodeling, which may play an important role in the occurrence of arrhythmia of heart failure.