全脑缺血再灌注损伤老龄大鼠海马胆碱能抗炎通路的变化

Changes in cholinergic anti-inflammatory pathway in hippocampi in aged rats with global cerebral ischemia/reperfusion injury

目的：评价全脑缺血再灌注损伤老龄大鼠海马胆碱能抗炎通路的变化。方法老龄雄性SD大鼠120只，18～22月龄，体重450～600 g ，采用随机数字表法，将其分为2组（ n＝60）：假手术组（S组）和全脑缺血再灌注组（I/R组）。I/R组采用四血管阻断法制备大鼠全脑缺血再灌注损伤模型。分别于再灌注1、3、5和7 d时处死15只大鼠，取脑组织，测定海马CA1区神经元凋亡率、α7烟碱型乙酰胆碱受体（α7nAChR）、胆碱乙酰基转移酶（ChAT）、TNF-α和IL-1β表达。结果与S组比较，I/R组再灌注不同时点海马组织神经元凋亡率升高，α7nAChR、ChAT、TNF-α和 IL-1β表达上调（ P＜0.05或0.01）；再灌注期间海马组织α7nAChR和ChAT表达逐渐上调，到再灌注5 d时达高峰（ P＜0.05）。结论全脑缺血再灌注损伤老龄大鼠海马胆碱能抗炎通路激活，该通路激活是抑制脑组织过度炎性反应的内源性机制。

Objective To evaluate the changes in cholinergic anti-inflammatory pathway in hippocampi global in aged rats with cerebral ischemia/reperfusion （I/R ） injury .Methods One hundred and twenty male Sprague-Dawley rats , aged 18-22 months ,weighing 450-600 g ,were randomly divided into 2 groups （ n= 60 each）：sham operation group （group S） and global cerebral I/R group （group I/R） .The animals were anesthetized with intraperitoneal 10% chloral hydrate 0.4 ml/100 g .Global cerebral I/R was induced by 4-vessel occlusion method described by Pulsinelli .Fifteen rats were sacrificed at 1 ,3 ,5 and 7 days of reperfusion ,and brains were removed for determination of neuronal apoptosis and expression of α7 nicotinic acetylcholine receptor （α7nAChR ） , choline acetyltransferase （ChAT ） ,tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in the hippocampal CA1 region .The apoptosis rate was calculated .Results Compared with group S ,the apoptosis rate was increased and the expression of α7nAChR ,ChAT ,TNF-αand IL-1βwas up-regulated in group I/R （ P〈0.05 or 0.01 ） . The expression of α7nAChR and ChAT was up-regulated gradually during reperfusion and peaked at 5 day of reperfusion （ P〈 0.05 ） .Conclusion Global cerebral I/R injury can activate cholinergic anti-inflammatory pathway in aged rat hippocampi ,and the activation of this pathway is the endogenous mechanism of inhibition of excessive inflammatory responses in brain tissues .