增强中枢胆碱能神经系统活性对小鼠术后认知障碍的影响  

Effect of enhancing the activity of central cholinergic nervous system on postoperative cognitive dysfunction in mice

作　　者：王天海 朱红革 侯彦深 段文明 于婵娟 WANG Tianhai;ZHU Hongge;HOU Yanshen;DUAN Wenming;YU Chanjuan(Department of Anesthesiology, the Third Hospital Affiliated to Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China;the Second Department of Pulmonary Medicine, the Third Hospital Affiliated to Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830011, China)

机构地区：[1]新疆医科大学第三临床医学院麻醉科,新疆乌鲁木齐830011 [2]新疆医科大学第三临床医学院肺内二科,新疆乌鲁木齐830011

出　　处：《中国医药导报》2019年第18期17-20,41,F0004,共6页China Medical Herald

基　　金：新疆维吾尔自治区自然科学基金资助项目(2016D01C359)

摘　　要：目的评价增强小鼠中枢胆碱能神经系统活性对术后认知功能障碍(POCD)的影响及机制。方法选用45只C57BL/6小鼠,采用随机数字表法将其分为三组:空白组、手术+NS组、手术+Galan组,每组15只;后两组行单侧胫骨骨折内固定术建立POCD模型。手术+Galan组术后每日腹腔注射4 mg/kg中枢胆碱能神经活性增强剂加兰他敏干预,手术+NS组每日腹腔注射等量0.9%NaCl。空白组不进行手术及药物干预。术后第3天和第7天使用情景恐惧测试评估三组小鼠学习与记忆的行为学变化;术后第3天检测海马内小胶质细胞活化程度和细胞数量,检测海马区促炎性细胞因子白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)和抗炎性细胞因子(IL-4和IL-10)的表达情况。结果术后第3天行为学检测中,与空白组比较,手术+NS组和手术+Galan组冻结时间均显著减少(P <0.01);与手术+Galan组比较,手术+NS组冻结时间减少(P <0.05)。术后7 d,与空白组比较,手术+NS组冻结时间显著减少(P <0.01),且手术+NS组冻结时间短于手术+Galan组(P <0.05),而手术+Galan组与空白组比较,差异无统计学意义(P> 0.05)。术后3 d,手术+NS组分别与空白组和手术+Galan组比较,海马内小胶质细胞数量均显著增加(P <0.01),但空白组与手术+Galan组比较,差异无统计学意义(P> 0.05)。与空白组比较,手术+NS组IL-1β、IL-6和TNF-α显著升高(P <0.01),且其IL-1β、IL-6、TNF-α显著高于手术+Galan组(P <0.01或P <0.05)。空白组与手术+Galan组IL-1β、IL-6和TNF-α比较,差异无统计学意义(P> 0.05)。三组间IL-4和IL-10比较,差异无统计学意义(P> 0.05)。结论加强中枢胆碱能神经系统活性可以通过抑制海马区小胶质细胞的活化,减轻海马区炎性反应,从而改善小鼠术后认知能力。增强中枢胆碱能活性可能是早期POCD的治疗策略。Objective To evaluate the effect and mechanism of enhancing the activity of central cholinergic nervous system on postoperative cognitive dysfunction(POCD) in mice. Methods Forty-five C57 BL/6 mice were selected and divided into three groups by random number table method, blank group, operation +NS group, operation +Galan group,with 15 mice in each group. The latter two groups underwent internal fixation of unilateral tibial fracture to establish the model of postoperative cognitive dysfunction. In the operation +NS group, 0.9% NaCl was injected into the abdominal cavity every day. Postoperative intraperitoneal injection of central cholinergic neuroactivity enhancer Galan intervention. No surgical or medical intervention was performed in the blank group. The behavioral changes of learning and memory in three groups were assessed by the situational fear test on the third and seventh day after the operation. The activation degree and number of microglia cells in the hippocampus were detected on the third day after the operation.The expression of pro-inflammatory cytokines interleukin(IL)-1β, IL-6 and tumor necrosis factor-α(TNF-α) and anti-inflammatory cytokines(IL-4 and IL-10) in the hippocampus were detected. Results In the behavioral test3 days after the operation, compared with the blank group, the freezing time in the operation +NS group and the operation +Galan group was significantly reduced(P < 0.01). Compared with the operation +Galan group, the freezing time of the operation +NS group was reduced(P < 0.05). Seven days after the operation, the freezing time of the operation +NS group was significantly reduced compared with the blank group(P < 0.01), and the freezing time of the operation +NS group was shorter than that of the operation +Galan group(P < 0.05), while the difference between the operation +Galan group and the blank group was not statistically significant(P > 0.05). 3 days after the operation, the number of microglia cells in the hippocampus in the operation +NS group was significantly incre

关 键 词：术后认知功能障碍 胆碱能系统 炎性因子 小胶质细胞 

分 类 号：R749.2[医药卫生—神经病学与精神病学]