α7烟碱型胆碱能受体激动剂对体外循环致大鼠肺损伤影响及其机制研究

Effect ofα7 nicotinic acetylcholine receptors agonist on lung injury induced by cardiopulmonary bypass in rats and its mechanism

目的探讨α7烟碱型胆碱能受体(α7nAChR)激动剂对体外循环(CPB)致大鼠肺损伤的影响及机制。方法选取60只清洁级健康雄性SD大鼠为研究对象,采用随机数字表法将其分为假手术组(S组)、CPB组、α7nAChR激动剂(PNU 282987)+CPB组(PC组)、PNU282987+α7nAChR阻断剂(MLA)+CPB组(MC组)、PNU282987+JAK2-STAT3通道特异性抑制剂(AG490)+CPB组(AC组),每组各12只。观察各组病理学变化并进行肺损伤评分,计算肺湿/干重比值;采用酶联免疫吸附法检测肺组织中肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)水平;蛋白免疫印迹法检测α7nAChR、p-JAK2、p-STAT3蛋白表达情况。结果与S组比较,CPB组、PC组、MC组和AC组大鼠肺损伤评分、湿/干重比值、呼吸指数(RI)明显升高,氧合指数(OI)明显降低,差异均有统计学意义(P<0.05)。与CPB组比较,PC组肺损伤评分、湿重/干重比值、OI、RI明显降低;MC组OI明显降低,差异均有统计学意义(P<0.05)。与S组比较,CPB组、PC组、MC组、AC组α7nAChR、p-JAK2、p-STAT3蛋白的表达均增加,差异均有统计学意义(P<0.05)。与CPB组比较,PC组α7nAChR表达增加,p-JAK2及p-STAT3表达减少,差异均有统计学意义(P<0.05)。结论α7nAChR激动剂通过上调α7nAChR的表达抑制JAK2/STAT3信号通路,进而抑制CPB引起的炎症反应,减轻大鼠肺损伤,起到保护肺组织、改善肺功能的作用。

Objective To investigate the influence and potential mechanism of theα7 nicotinic acetylcholine receptor(α7nAChR)agonist in the lung injury in rats that induced by cardiopulmonary bypass(CPB).Methods A total of 60 healthy male SD rats were randomly divided into the sham operation group(S group),CPB group,α7nAChR agonist(PNU282987)+CPB group(PC group),PNU282987+α7nAChR blocker(MLA)+CPB group(MC group),PNU282987+JAK2-STAT3 pathway inhibitor(AG490)+CPB group(AC group),with 12 rats in each group.Pathological results were achieved and the lung injury degrees were scored.The wet/dry weight(W/D)ratios were calculated.Tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6 contents were detected by ELISA.Western blot was used to detect the expression ofα7nAChR,p-JAK2 and p-STAT3 proteins.Results Compared with S group,the lung injury score,wet/dry weight ratio,respirator index(RI)of the other four groups increased significantly and oxygenation index(OI)reduced significantly,with statistically significant differences(P<0.05).Compared with CPB group,the lung injury score,wet/dry weight ratio,OI and RI reduced significantly in PC group,OI reduced significantly in MC group,P<0.05.Compared with the S group,the CPB group,PC group,MC group and AC group all showed increased expression ofα7nAChR,p-JAK2 and p-STAT3,P<0.05.Compared with the CPB group,the expression ofα7nAChR increased and p-JAK2 and p-STAT3 reduced in the PC group,P<0.05.Conclusionα7nAChR agonist inhibited the JAK2/STAT3 signaling pathway by up-regulating the expression ofα7nAChR,thereby inhibiting the inflammatory response caused by CPB,reducing lung injury in rats,protecting lung tissues and improving lung function.