PUN282987对老龄大鼠全脑缺血再灌注损伤的影响

Effect of PUN282987 on global cerebral ischemia-reperfusion injury in aged rats

目的评价PUN282987对老龄大鼠全脑缺血再灌注损伤的影响。方法清洁级健康雄性SD大鼠120只，18～22月龄，体重450～600 g，采用随机数字表法分为3组（n＝40）：假手术组（S组）、全脑缺血再灌注组（I/R组）和α7烟碱型乙酰胆碱受体（α7nAChR）激动剂PUN282987组（PUN组）。I/R组和PUN组采用四动脉阻断法制备大鼠全脑缺血再灌注损伤模型，PUN组于缺血前腹腔注射PUN282987 2.4 mg/kg。分别于再灌注1、5、12和24 h时随机取10只大鼠处死，取脑组织，测定海马CA1区神经元凋亡率、α7nAChR、胆碱乙酰基转移酶（ChAT）、TNF-α和IL-1β的表达。结果与S组比较，I/R组和PUN组各时点海马神经元凋亡率升高，α7nAChR、ChAT、TNF-α和IL-1β表达上调（P〈0.05）；与I/R组比较，PUN组各时点海马神经元凋亡率降低，α7nAChR和ChAT表达上调，TNF-α和IL-1β表达下调（P〈0.05）。结论PUN282987可减轻老龄大鼠全脑缺血再灌注损伤。

Objective To evaluate the effect of PUN282987 on global cerebral ischemia-reperfusion （I/R） injury in aged rats. Methods One hundred and twenty pathogen-free healthy male Sprague- Dawley rats, aged 18-22 months, weighing 450-600 g, were divided into 3 groups （n=40 each） using a random number table： sham operation group （group S）, global cerebral I/R group （group I/R） and α7 nicotinic acetylcholine receptor （ct7nAChR） agonist PNU282987 group （group PUN）. The animals were anesthetized with intraperitoneal 10% chloral hydrate 0.4 ml/100g, and global cerebral I/R was produced by 4-vessel occlusion technique in I/R and PUN groups. PUN282987 2.4 mg/kg was injected intraperitoneally before isehemia in group PUN. At 1, 5, 12 and 24 h of reperfusion, 10 rats were randomly selected in each group and then sacrificed, and the brains were removed for detection of the neuronal apoptosis and for determination of the expression of α7nAChR, choline acetyltransferase （CHAT） , tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in the hippocampal CA1 region. Apoptosis rate was calculated. Results Compared with group S, the apoptosis rate was significantly increased, and the expression of α 7nAChR, CHAT, TNF-α and IL-1β was up-regulated at each time point in I/R and PUN groups （P〈 0.05）. Compared with group I/R, the apoptosis rate was significantly decreased, the expression of α 7nAChR and ChAT was up-regulated, and the expression of TNF-α and IL-1β was down-regulated at each time point in group PUN （P〈0.05）. Conclusion PUN282987 can reduce global cerebral I/R injury in aged rats.