目的探讨盐酸戊乙奎醚(PHC)后处理对缺血再灌注大鼠心肌炎症反应的影响,以及PHC后处理抗炎症反应的调控通路。方法 24只实验Wistar大鼠,按随机数字表法分为3组:假手术组(Sham组),大鼠冠状动脉左前降支穿线不结扎;缺血再灌注(I/R组)组,大鼠冠状动脉左前降支结扎30 min,再灌注3 h;PHC后处理组(Post组),再灌注即刻大鼠尾静脉注射PHC(1 mg/kg)。各组在3个不同的时间点抽血,采用ELISA法检测血清炎症因子[肿瘤坏死因子-α(TNF-α)和白细胞介素-8(IL-8)]含量。实验结束,采用Western blot的方法,检测炎症调节蛋白[核因子κB抑制蛋白α(IκB-α)和核因子-κB(NF-κB)]的表达。结果与Sham组比较,I/R组血清TNF-α和IL-8含量明显增加,心肌组织IκB-α表达减少,NF-κB表达增加(P〈0.05)。与I/R组比较,Post组血清TNF-α和IL-8含量明显减少,心肌组织IκB-α表达增加,NF-κB表达减少(P〈0.05)。结论 PHC后处理能够抑制心肌I/R导致的炎症反应,可能的机制是通过调控经典的NF-κB信号通路。
Objective To investigate the effect and probable mechanism of anti-inflammatory responses of penehyclidine hydrochloride( PHC) postconditioning in rat myocardial ischemia-reperfusion( I/R). Methods Twenty-four Wistar rats were randomly divided into 3 groups,Group Sham( the left anterior descending artery of the was not ligated),Group I/R( the left anterior descending artery ligated for 30 min,and reperfusion for 3h) and Group PHC postconditioning( Group Post,PHC was injected into rat tail vein at the beginning of reperfusion). The serum levels of inflammatory factors( TNF-α and IL-8) were measured by ELISA at three different time points. At the end of the experiment,Western blot method was applied to detect the expression of inflammatory regulatory proteins( IκB-α and NF-κB). Results Compared with Group Sham,the levels of TNF-α and IL-8 were significantly increased in Group I/R,with reduced expression of IκB-α and increased expression of NF-κ B( P〈0. 05). Compared with Group I/R,the levels of TNF-α and IL-8 were significantly reduced in Group Post( P〈0. 05). Compared with Group I/R,the expression of IκB-α was significantly increased and the expression of NF-κ B was significantly reduced in Group Post( P〈0. 05).Conclusion PHC postconditioningcan inhibits the inflammatory reaction induced by myocardial I/R,probably via the inhibition of canonical NF-кB pathway.