老龄大鼠术后早期认知功能障碍与神经调节蛋白1β的关系

Relationship between early postoperative cognitive dysfunction and neuromodulator protein 1βin aged rats

目的评价老龄大鼠术后早期认知功能障碍与神经调节蛋白1β(NRG1β)的关系。方法清洁级健康雄性SD大鼠30只,18~20月龄,体重600~700 g,侧脑室置管成功后,采用随机数字表法分为3组(n=10):对照组(C组)、手术组(O组)和NRG1β(N组)。N组于术前1 d侧脑室注射NRG1β0.5μg/kg。于术后第3天行Morris水迷宫实验,随后处死大鼠,分离海马组织,采用Western blot法检测核蛋白NF-κB p65的表达,ELISA法检测IL-1β和TNF-α含量。结果与C组比较,O组和N组术后逃避潜伏期延长,海马核蛋白NF-κB p65表达上调,IL-1β和TNF-α含量升高(P<0.05);与O组比较,N组术后逃避潜伏期缩短,海马核蛋白NF-κB p65表达下调,IL-1β和TNF-α含量降低(P<0.05)。结论NRG1β可能通过抑制NF-κB通路激活,抑制炎症反应,参与了老龄大鼠术后早期认知功能障碍的内源性保护机制。

Objective To evaluate the relationship between early postoperative cognitive dysfunction and neuromodulator protein 1β(NRG1β)in aged rats.Methods Pathogen-free healthy male Sprague-Dawley rats,aged 18-20 months,weighing 600-700 g,were divided into 3 groups(n=10 each)using a random number table method:control group(group C),operation group(group O)and NRG1βgroup(group N).Exploratory laparotomy was performed in group O and group N.NRG1β0.5μg/kg was slowly injected into the lateral ventricle on 1 day before surgery in group N,while the equal volume of 0.1 mol/L phosphate buffer solution was given instead in C and O groups.Learning and memory function was assessed using Morris water maze test performed at day 3 after operation.The rats were then sacrificed,and the hippocampi were removed for determination of the expression of nuclear factor kappa B(NF-κB)p65(by Western blot)and contents of interleukin-1beta(IL-1β)and tumor necrosis factor-alpha(TNF-α)(by enzyme-linked immunosorbent assay).Results Compared with group C,the postoperative escape latency was significantly prolonged,the expression of NF-κB p65 was up-regulated,and the contents of IL-1βand TNF-αwere increased in group O and group N(P<0.05).Compared with group O,the postoperative escape latency was significantly shortened,the expression of NF-κB p65 was down-regulated,and the contents of IL-1βand TNF-αwere decreased in group N(P<0.05).Conclusion NRG1βis involved in the endogenous protective mechanism of early postoperative cognitive dysfunction probably by inhibiting the activation of NF-κB pathway and inhibiting inflammatory responses in aged rats.