α7烟碱型胆碱能受体激动剂对体外循环致大鼠急性肺损伤的影响

摘要

目的 评价α7烟碱型胆碱能受体(ot7nAChR)激动剂对体外循环(CPB)致大鼠急性肺损伤的影响.方法 清洁级健康成年雄性SD大鼠18只,体重350～400 g,采用随机数字法分为3组(n=6):假手术组(S组)、CPB组和α7nAChR激动剂PHA568487组(PHA组).S组不进行CPB,机械通气60 min;PHA组于CPB前30 min腹腔注射PHA568487 0.8 mg/kg(用生理盐水稀释至2ml),然后CPB60min;CPB组于CPB前30 min腹腔注射生理盐水2 ml后CPB 60 min.于CPB 2 h时,取颈静脉血样,采用ELISA检测血清IL-6和TNF-α浓度;测定肺组织湿重/干重(W/D)比值;HE染色后观察肺组织病理学结果;采用Western blot法检测基质金属蛋白酶9(MMP-9)表达.结果 与S组相比,CPB组和PHA组肺组织W/D比值、血清TNF-α和IL-6浓度升高,肺组织MMP-9表达上调(P＜0.05).与CPB组相比,PHA组肺组织W/D比值、血清TNF-α和IL-6浓度降低,肺组织MMP-9表达下调(P＜0.05),肺组织病理学损伤减轻.结论 α7nAChR激动剂可减轻CPB致大鼠急性肺损伤,其机制可能与下调MMP-9的表达,抑制全身炎症反应有关.%Objective To evaluate the effect of α7 nicotinic acetylcholine receptor (α7nAChR)agonists on lung injury caused by cardiopulmonary bypass (CPB) in rats.Methods Eighteen healthy clean-grade adult male Sprague-Dawley rats,weighing 350-400 g,were divided into 3 groups (n =6 each)using a random number table method:sham operation group (group S),CPB group and α7nAChR agonist PHA568487 group (group PHA).The rats underwent no CPB and were mechanically ventilated for 60 min in group S.PHA568487 0.8 mg/kg (diluted to 2 ml in normal saline) was intraperitoneally injected at 30 min before CPB,and then CPB was performed for 60 min in group PHA.Normal saline 2 ml was intraperitoneally injected at 30 min before CPB,and then CPB was performed for 60 min in group CPB.Blood samples were collected from the internal jugular vein for determination of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations by enzyme-linked immunosorbent assay.Lung tissues were obtained for microscopic examination of the pathologic changes and for determination of wet/dry weight ratio (W/D ratio) and matrix metalloproteinase-9 (MMP-9) expression (by Western blot).Results Compared with group S,the W/D ratio and serum concentrations of TNF-α and IL-6 were significantly increased,and the expression of MMP-9 was up-regulated in CPB and PHA groups (P＜0.05).Compared with group CPB,the W/D ratio and serum concentrations of TNF-α and IL-6 were significantly decreased,the expression of MMP-9 was down-regulated (P＜0.05),and the pathological changes of lung tissues were significantly attenuated in group PHA (P＜0.05).Conclusion α7nAChR agonists can reduce the acute lung injury caused by CPB in rats,and the mechanism may be related to down-regulating MMP-9 expression and inhibiting systemic inflammatory responses.