益母草碱基由CaMKⅡ/Cx36信号对七氟醚诱导幼鼠突触可塑性的改善作用  

Effects of Leonurine on synaptic plasticity of sevoflurane-induced infant mice based on CaMKⅡ/Cx36 signal

作　　者：肖志博[1] 金辉[1] 谢海[1] 符少川[1] 葛树胜 XIAO Zhibo;JIN Hui;XIE Hai(Department of Anesthesiology,The First Affiliated Hospital of Hainan Medical University,Hainan,Haikou 570102,China)

机构地区：[1]海南医学院第一附属医院麻醉科,海口市570102

出　　处：《河北医药》2022年第24期3701-3705,共5页Hebei Medical Journal

基　　金：国家自然科学基金委员会资助项目(编号:81660195);海南省卫生健康行业科研项目(编号:19A200057)。

摘　　要：目的探讨益母草碱对七氟醚麻醉幼鼠海马神经元突触可塑性和认知功能损伤的影响及其可能的机制。方法60只7 d龄幼鼠,随机分为对照组,七氟醚组,益母草碱-低、中、高剂量组,每组12只。非对照组幼鼠以3%七氟醚麻醉6 h后,取益母草碱组幼鼠分别给予2.5、5、10 mg/kg益母草碱溶液。连续治疗28 d,采用Morris水迷宫评价各组幼鼠学习记忆能力;采用高尔基染色测定海马神经元树突棘状态;采用电生理测试评估海马区长时程电位增强;采用Western blotting测定各组幼鼠海马中CaMKⅡ、Cx36蛋白表达。结果与对照组相比,七氟醚组幼鼠逃避潜伏期明显增加,穿越平台次数与第Ⅰ象限停留时间明显减少(P<0.05);与此同时,海马神经元树突棘长度与密度降低,长时程电位水平降低,p-CaMKⅡ、Cx36蛋白表达明显减少(P<0.05)。与七氟醚组相比,益母草碱-H组水迷宫逃避潜伏期明显下降,穿越平台次数与第Ⅰ象限停留时间明显增加(P<0.05);此外,益母草碱-H组树突棘长度和密度明显增加,长时程电位水平明显上调,p-CaMKⅡ、Cx36蛋白表达明显增加(P<0.05)。结论益母草碱能通过上调CaMKⅡ/Cx36表达和增加树突棘长度与密度,逆转七氟醚诱导幼鼠突触可塑性降低,提高幼鼠学习记忆能力。Objective To investigate the effects of Leonurine on the synaptic plasticity and cognitive impairment of hippocampal neurons in sevoflurane-anesthetized infant mice and corresponding possible mechanism.Methods Sixty 7d-old pups were randomly divided into the control group,sevoflurane group,and Leonurine-low-,medium-,high-dose groups with 12 cases in each group.The infant mice were respectively given 2.5,5,10mg/kg of Leonurine solution following the non-control infant mice received anesthesia with 3%sevoflurane for 6 hours.Morris water maze was applied to evaluate the learning and memory capacities of infant mice after continuous treatment for 28 days;Golgi-Cox staining was applied to determine the state of hippocampal dendritic spines;and electrophysiological test was used to evaluate long-term potential(LTP)in the hippocampus;CaMKⅡand Cx36 protein expressions in the hippocampus were detected by Western blotting.Results Compared with the control group,the escape latency in the sevoflurane group was significantly longer,the number of cross-platform and residence duration in the first quadrant were significantly reduced(P<0.05).Moreover,the length and density of hippocampal dendritic spine were lowered,LTP level was reduced,and the expression of p-CaMKⅡand Cx36 protein were significantly reduced(P<0.05).Compared with the sevoflurane group,the escape latency in Leonurine high-dose group significantly shorter(P<0.05),and the number of cross-platform and residence duration in the first quadrant significantly increased(P<0.05).Furthermore,the length and density of hippocampal dendritic spines in the Leonurine high-dose group significantly increased,LTP level increased,and the expression of p CaMKⅡand Cx36 protein significantly increased(P<0.05).Conclusion Leonurine can reverse the decreased synaptic plasticity of sevoflurane induced infant mice by up-regulating the expression of CaMKⅡ/Cx36 and increasing the length and density of hippocampal dendritic spines,leading to improvement of learning and memory ability

关 键 词：益母草碱 七氟醚 幼鼠 突触可塑性 认知功能 

分 类 号：R619[医药卫生—外科学]