α7烟碱型乙酰胆碱受体在胫骨折断老龄大鼠术后认知功能障碍中的作用

Role of α7nAChR in postoperative cognitive dysfunction in aged rats with tibial fracture

目的评价α7烟碱型乙酰胆碱受体(α7nAChR)在胫骨折断老龄大鼠术后认知功能障碍中的作用.方法清洁级健康雄性SD大鼠150只,18~22月龄,体重440~580 g,采用随机数字表法分为5组(n=30):对照组(C组)、假手术组(S组)、胫骨折断组(T组)、生理盐水组(N组)和α7nAChR激动剂PUN282987组(P组).C组不做任何处理;S组腹腔注射10%水合氯醛0.4 ml/100 g;T组采用胫骨折断术;P组于胫骨折断前5 min腹腔注射PUN2829872.4 mg/kg;N组胫骨折断前5 min给予腹腔注射等量生理盐水.于术后7 d进行Morris水迷宫实验;于术后1、3和7 d时采用HE染色观察海马CA3区病理学结果;采用Western blot法检测α7nAChR、胆碱乙酰转移酶(ChAT)、TNF-α和IL-1β的表达.结果与C组比较,T组、N组和P组术后逃避潜伏期和游泳路径延长,术后各时点海马α7nAChR、ChAT、TNF-α和IL-1β表达上调(P<0.05),S组上述指标差异无统计学意义(P>0.05);与T组比较,P组术后逃避潜伏期和游泳路径缩短,术后各时点海马α7nAChR和ChAT表达上调,TNF-α和IL-1β表达下调(P<0.05),N组上述指标差异无统计学意义(P>0.05),P组海马组织病理学损伤减轻.结论α7nAChR拮抗参与了胫骨折断老龄大鼠术后认知功能障碍的形成.

Objective To evaluate the role of α7 nicotinic acetylcholine receptor (α7nAChR) in postoperative cognitive dysfunction in aged rats with tibial fracture. Methods One hundred and fifty clean-grade healthy male Sprague-Dawley rats, aged 18-22 months, weighing 440-580 g, were divided into 5 groups ( n=30 each ) using a random number table method: control group ( group C ), sham operation group ( group S), tibial fracture group ( group T), normal saline group ( group N) and α7nAChR agonist PUN282987 group (group P). Group C received no treatment. Ten percent chloral hydrate 0. 4 ml/100 g was injected intraperitoneally in group S. Group T underwent tibial fracture. PUN2829872. 4 mg/kg was in-traperitoneally injected at 5 min before tibial fracture in group P . The equal volume of normal saline was giv-en at 5 min before tibial fracture in group N. Morris water maze test was performed at day 7 after surgery. At days 1, 3 and 7 after surgery, the pathological changes of the hippocampal CA3 region were observed by haematoxylin and eosin staining, and the expression of α7nAChR, choline acetyltransferase ( ChAT ), tumor necrosis factor-α( TNF-α) and interleukin-1β( IL-1β) in the hippocampal CA3 region was measured by Western blot. Results Compared with group C, the postoperative escape latency and swimming dis-tance were significantly prolonged, and the expression of α7nAChR, ChAT, TNF-α and IL-1β was up-regulated at each time point after operation in T, N and P groups ( P<0. 05), and no significant change was found in the parameters mentioned above in group S ( P>0. 05). Compared with group T, the postoper-ative escape latency and swimming distance were significantly shortened, and the expression of α7nAChR and ChAT was up-regulated and the expression of TNF-α and IL-1β was down-regulated at each time point after operation in group P ( P<0. 05), no significant change was found in the parameters mentioned above in group N ( P>0. 05), and the pathological changes of the hippocampal CA3 region were significantly at-tenuated in group P. Conclusion α7nAChR antagonism is involved in the development of postoperative cognitive dysfunction in aged rats with tibial fracture.