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| κ阿片受体激动剂对心肺转流大鼠术后认知功能及α7nAChR表达的影响 |
| Protective effects of kappa opioid receptor agonist on postoperative cognitive function and the expression of α7nAChR induced by cardiopulmonary bypass in rats |
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| DOI：10.12089/jca.2018.10.014 |
| 中文关键词: κ-阿片受体激动剂 认知功能 心肺转流 α7烟碱型乙酰胆碱受体 水迷宫 |
| 英文关键词: Kappa opioid receptors agonist Cognitive function Cardiopulmonary bypass α7 Nicotinic acetylcholine receptors Water maze |
| 基金项目:国家自然科学基金面上项目(81471121) |
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| 中文摘要: |
目的 探讨κ阿片受体(kappa opioid receptors,KORs)激动剂U50488H对心肺转流(CPB)后大鼠认知功能及α7烟碱型乙酰胆碱能受体(α7nAChR)表达的影响。
方法 成年雄性SD大鼠32只,体重400～450 g,随机分为四组: Sham组(S组)、CPB组(C组)、CPB+U50488H 组(K组)、CPB+KORs拮抗剂Nor-BNI+U50488H组(N组),每组8只。四组大鼠于术前5 d开始进行水迷宫训练,每天4次。S组不建模型,动静脉穿刺后进行机械通气60 min,其余三组CPB 60 min。术后1 d进行Morris水迷宫实验,随后处死大鼠，采集血清，取海马组织。采用ELISA法检测血清IL-1β、TNF-α、S100β浓度、海马ACh含量及ChAT和AchE活性;采用Western blot 法检测海马α7nAChR蛋白含量。
结果 与S组比较,C、K和N组逃避潜伏期明显延长,穿越平台次数明显减少,目标象限游泳距离和停留时间明显缩短(P<0.05);血清IL-1β、TNF-α和S100β浓度明显升高,海马α7nAChR蛋白含量明显降低(P<0.05)。与C组比较,K组逃避潜伏期明显缩短,穿越平台次数明显增多,目标象限游泳距离和停留时间明显延长(P<0.05);血清IL-1β、TNF-α和S100β浓度明显降低,海马α7nAChR蛋白含量明显升高(P<0.05)。与S组比较,C组、N组海马Ach含量及ChAT活性明显降低,AchE活性明显升高。与C组比较,K组海马Ach含量及ChAT活性明显升高,AchE活性明显降低(P<0.05)。
结论 KORs激动剂激活胆碱能抗炎通路,上调α7nAChR的表达,减轻炎症反应,从而改善CPB后大鼠认知功能。 |
| 英文摘要: |
Objective To investigate the protective effect of κ-opioid receptor (KORs) agonist U50488H on postoperative cognitive function in rats after cardiopulmonary bypass (CPB) and the relationship with the cholinergic anti-inflammatory pathway (CAP).
Methods Thirty-two adult male SD rats, weighing 400 - 450 g, were randomly divided into 4 groups: sham group (group S), CPB group (group C), CPB+U50488H group (group K) and CPB+KORs antagonists Nor-BNI+U50488H group (group N), 8 rats in each group. The rats of the four groups were trained in water maze for five days, four times once a day before operation. In group S, the model was not established and mechanical ventilation was performed for 60 min after puncture. CPB was maintained for 60 min in the remaining three groups. The rats of each group were tested the cognitive function by the Morris water maze experiment one day after CPB, then the plasma samples and hippocampus were collected. The levels of plasma IL-1β, TNF-α and S100β, hippocampus ACh levels and ChAT, AchE activitives were detected by ELISA; the levels of hippocampus α7nAChR was detected by Western blot.
Results Compared with group S, the average latency were significantly increased, the average number of cross platform were significantly decreased, the distance and time of rats swiming in the target quardrant were significantly shortened, the levels of plasma IL-1β, TNF-α and S100β were increased, the levels of hippocampus α7nAChR was decreased in groups C, K and N (P < 0.05). Compared with group C, the average latency were significantly decreased, the average number of cross platform were significantly increased, the distance and time of rats swiming in the target quardrant were significantly extended, the levels of plasma IL-1β, TNF-α and S100β were decreased, the levels of hippocampus α7nAChR was increased in group K (P < 0.05). Compared with group S, the levels of ACh and activities of ChAT were descended, AchE activity was enhanced in groups C and K (P < 0.05). Compared with group C, the levels of ACh and activities of ChAT were enhanced, AchE activity was descended in group K (P < 0.05). There was no significantly difference neither between groups K and S nor groups N and C.
Conclusion KORs agonist activation CAP raises the expression of α7nAChR, relieves inflammation of the rats after CPB, then improves the postoperative cognitive function. |
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