β-淀粉样蛋白在老龄大鼠术后认知功能障碍中的作用及石杉碱甲的干预作用

Role of amyloid beta-protein in postoperative cognitive dysfunction and effect of huperzine A on cognitive dysfunction in aged rats

目的评价β-淀粉样蛋白(Aβ)在老龄大鼠术后认知功能障碍中的作用及石杉碱甲的干预作用。方法选择健康老年雄性SD大鼠72只,20~22月龄,体重550~700 g,采用随机数字表法分为对照组(C组)、术后认知功能障碍组(P组)和石杉碱甲组(H组),每组24只。P组和H组采用脾切除术建立老龄大鼠术后认知功能障碍模型,C组不行手术。H组和C组在手术前给予石杉碱甲0.15 mg·kg^(-1)·d^(-1)灌胃,连续3 w,P组按体重给予等容量生理盐水。分别于脾切除手术后第1、3和7天时(T1~T3)每组随机取8只大鼠进行Morris水迷宫测试认知功能;同时采用酶联免疫吸附实验(ELISA)测定大鼠血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6和IL-10浓度;并取海马组织,采用Western印迹法测定海马Aβ表达。结果与C组比较,P组和H组大鼠逃避潜伏期延长(H组T2、T3时点除外),穿越平台次数减少,血清TNF-α、IL-6及IL-10浓度升高,海马Aβ表达上调(P<0.05);与P组比较,H组大鼠逃避潜伏期缩短,穿越平台次数增加,血清TNF-α及IL-6浓度降低,IL-10浓度升高,海马Aβ表达下调(P<0.05)。结论石杉碱甲可减轻老龄大鼠术后认知功能障碍,机制可能与其降低炎性反应及下调海马组织Aβ表达有关。

Objective To investigate the role of amyloid beta-protein(Aβ) in postoperative cognitive dysfunction(POCD) and effect of huperzine A on cognitive dysfunction in aged rats.Methods Seventy-two male Sprague-Dawley rats,aged 20 ~ 22 months,weighting550 ~ 700 g,were randomly divided into 3 groups( n = 24): control group( group C),postoperative cognitive dysfunction group( group P)and huperzine A group( group H). Splenectomy were performed to create POCD model in group P and H. Rats in group H were administered huperzine A for three weeks before operation,after three weeks rats in group P and group H received splenectomy. Eight animals from each group were selected on 1,3 and 7 d( T1-T3) after operation respectively underwent Morris water-maze test for assessment of the cognitive function. The escape latency and frequency of crossing the original platform were recorded. And arterial blood samples were taken for determination of the levels of serum TNF-α,IL-6 and IL-10.The hippocampal was isolated,and expression of Aβ in hippocampal were detected by Western blot.Results Compared with group C,the escape latency was prolonged,the frequency of crossing the original platform was decreased,the serum TNF-α,IL-6 and IL-10 were increased,the expression of Aβ was increased in groups P and H( P<0.05). Compared with group P,the escape latency was shortened,the frequency of crossing the original platform was increased,the serum TNF-α and IL-6 were decreased,serum IL-10 was increased,and the expression of Aβ was decreased in group H( P<0.05).Conclusions Huperzine A could attenuate POCD in aged rats,the mechanism might be associated with reduction the inflammatory response and down-expression of Aβ in hippocampal.