摘要
目的评价海马Wnt/β-catenin信号通路在氯化锂预处理改善老龄大鼠术后认知功能中的作用。方法清洁级健康雄性老龄SD大鼠100只,18月龄,体重540~650 g,采用随机数字表法分为5组(n=20):对照组(C组)、手术组(S组)、氯化锂预处理组(L组)、sFRP-1组(F组)及氯化锂预处理+sFRP-1组(L+F组)。L组和L+F组术前连续5 d腹腔注射氯化锂2 mmol/kg,1次/d;F组和L+F组术前1 d脑室注射sFRP-1(浓度10 μg/ml)蛋白液10 μl。于术后1 d每组随机处死10只大鼠,取海马组织,采用Western blot法检测海马组织磷酸化糖原合成酶激酶-3β(p-GSK-3β)、β-catenin及Wnt的表达。术后3~7 d行Morris水迷宫,术后第7天采用ELISA法检测脑脊液β-淀粉样蛋白42(Aβ-42)和磷酸化tau-181蛋白(p-tau-181)浓度。结果与C组比较,其余4组术后3~7 d逃避潜伏期延长,脑脊液Aβ-42浓度升高,S组海马Wnt、p-GSK-3β和β-catenin表达下调,L组和L+F组海马Wnt、p-GSK-3β和β-catenin表达上调,S组和L+F组脑脊液p-tau-181浓度升高(P〈0.05)。与S组比较,L组术后3~7 d和L+F组术后5~7 d逃避潜伏期缩短,L组和L+F组海马Wnt、p-GSK-3β和β-catenin表达上调,脑脊液Aβ-42和p-tau-181浓度降低(P〈0.05)。与L组比较,L+F组术后3~6 d逃避潜伏期延长,海马Wnt、p-GSK-3β和β-catenin表达下调,脑脊液p-tau-181浓度升高(P〈0.05)。与F组比较,L+F组术后3~7 d逃避潜伏期缩短,海马Wnt、p-GSK-3β和β-catenin表达上调,脑脊液Aβ-42和p-tau-181浓度降低(P〈0.05)。结论氯化锂预处理改善老龄大鼠术后认知功能的部分机制与激活Wnt/β-catenin信号通路有关。
Objective To evaluate the role of Wnt/β-catenin signaling pathway in lithium chloride preconditioning-induced improvement in postoperative cognitive function of aged rats.Methods A total of 100 pathogen-free healthy male Sprague-Dawley rats, aged 18 months, weighing 540-650 g, were divided into 5 groups(n=20 each)using a random number table: control group(group C), surgery group(group S), lithium chloride preconditioning group(group L), secreted frizzled-related protein 1(sFRP-1) group(group F)and lithium chloride preconditioning plus sFRP-1 group(group L+ F). Lithium chloride 2 mmol/kg was intraperitoneally injected once a day for 5 consecutive days before operation in L and L+ F groups.In F and L + F groups, sFRP-1 10 μl(concentration 10 μg/ml)was injected into the ventricle at 1 day before operation.Ten rats in each group were randomly sacrificed at 1 day after operation, and the hippocampi were removed for determination of the expression of phosphorylated glycogen synthase kinase-3 beta(p-GSK-3β), β-catenin and Wnt in hippocampal tissues(by Western blot). The rest rats underwent Morris water maze test at day 3-7 after operation, and the concentrations of amyloid beta 42(Aβ-42)and phosphorylated tau-181 protein(p-tau-181)in cerebrospinal fluid(CSF)were detected by enzyme-linked immunosorbent assay at day 7 after operation.Results Compared with group C, the escape latency was significantly prolonged at 3-7 days after operation, and the concentration of Aβ-42 in CSF was increased in the other four groups, and the expression of Wnt, p-GSK-3β and β-catenin in hippocampal tissues was down-regulated in group S, the expression of Wnt, p-GSK-3β and β-catenin in hippocampal tissues was significantly up-regulated in L and L+ F groups, and the concentration of p-tau-181 in CSF was significantly increased in S and L+ F groups(P〈0.05). Compared with group S, the escape latency was significantly shortened at 3-7 days after operation in group L and at 5-7 days after operation in group L+ F, and the expression of Wnt, p-GSK-3β and β-catenin was significantly up-regulated, and the concentrations of Aβ-42 and p-tau-181 in CSF were decreased in L and L+ F groups(P〈0.05). Compared with group L, the escape latency was significantly prolonged at 3-6 days after operation, the expression of Wnt, p-GSK-3β and β-catenin was down-regulated, and the concentration of p-tau-181 in CSF was increased in group L+ F(P〈0.05). Compared with group F, the escape latency was significantly shortened at 3-7 days after operation, the expression of Wnt, p-GSK-3β and β-catenin was up-regulated, and the concentrations of Aβ-42 and p-tau-181 in CSF were decreased in group L+ F(P〈0.05).Conclusion The mechanism by which lithium chloride preconditioning improves in postoperative cognitive function is partially related to activating Wnt/β-catenin signaling pathway in aged rats.
作者
陈英
周志东
张静
张列亮
魏根
徐国海
华福洲
Chen Ying;Zhou Zhidong;Zhaag Jing;Zhang Lieliang;Wei Gen;Xu Guohai;Hua Fuzou(Department of Anesthesiology, Second Affiliated Hospital, Nanchang University Key Laboratory of Anesthesiology in Jiangxi Province, Nanchang 330006, Chin)
出处
《中华麻醉学杂志》
CSCD
北大核心
2017年第12期1493-1497,共5页
Chinese Journal of Anesthesiology
基金
国家自然科学基金(81560193)
南昌大学第二附属医院青年科学基金(2016YNQN12019)