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中枢胆碱能神经元变性对小鼠肝叶切除术后认知功能的影响

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目的 观察中枢胆碱能神经元变性对小鼠肝叶切除术后认知功能的影响。方法 将C57BL/6小鼠随机分为麻醉组、手术组、多奈哌齐组、mu-p75-sap组、对照组,每组5只。麻醉组动物吸入2。6%七氟烷、30%氧气、70%氮气混合气体6 h麻醉;手术组、多奈哌齐组、mu-p75-sap组采用同法麻醉并接受肝叶切除手术,其中多奈呱齐组术前给予选择性可逆中枢乙酰胆碱酯酶(AChE)抑制剂多奈哌齐5 mg/kg灌胃4周,mu-p75-sap组麻醉后向小鼠各侧脑室双侧各注射免疫毒素mu-p75-sap 0。8 µg制作胆碱能神经元变性模型。对照组动物不进行手术和麻醉操作。采用Morris水迷宫实验检测小鼠学习和记忆能力,采用考马斯亮兰蛋白测定试剂盒检测各组海马组织中枢胆碱能神经生物标志物[胆碱乙酰转移酶(ChAT)、AChE、乙酞胆碱(Ach)]。结果 与对照组相比,手术组逃逸潜伏期延长,AChE表达增高,停留时间、穿越平台次数和海马组织ChAT、Ach表达减少(P均<0。05)。与手术组相比,多奈哌齐组逃逸潜伏期缩短、停留时间和穿越平台次数增多、AChE表达降低、ChAT和Ach表达增高,mu-p75-sap组小鼠逃逸潜伏期延长、停留时间和穿越平台次数减少、ChAT和Ach表达降低、AChE表达增高(P均<0。05)。结论 肝叶切除术可影响小鼠术后认知功能,中枢胆碱能神经元变性可加重对术后认知功能的影响,可能会导致术后认知障碍的发生发展。
Effect of central cholinergic neuron degeneration on postoperative cognitive function in mice after hepatolobectomy
Objective To explore the effect of central cholinergic neuron degeneration on postoperative cognitive function in mice after hepatolobectomy.Methods C57BL/6 mice were randomly divided into the anesthesia group,sur-gery group,donepezil group,mu-p75-sap group,and control group,with 5 mice in each group.The animals in the anes-thesia group were anesthetized by inhaling a mixture of 2.6%sevoflurane,30%oxygen,and 70%nitrogen for 6 h.Mice in the surgery group,donepezil group,and mu-p75-sap group underwent hepatic lobectomy under the same anesthesia meth-od,with the donepezil group receiving selective reversible central acetylcholinesterase(AChE)inhibitor donepezil 5 mg/kg for 4 weeks before surgery,and the mu-p75-sap group receiving bilateral intraventricular injection of immunotoxin mu-p75-sap 0.8 µg per side to create a model of cholinergic neuron degeneration after anesthesia.Mice in the control group did not undergo any surgery or anesthesia procedures.The Morris water maze experiment was used to assess the learning and memory abilities of the mice,and the Cortez Bright Lanthanide protein assay kit was used to detect central cholinergic neurobiomarkers[choline acetyltransferase(ChAT),AChE,and acetylcholine(Ach)]in the hippocampal tissues of each group.Results Compared with the control group,the surgery group showed a prolonged escape latency,increased AChE expression,decreased retention time,platform crossings,and reduced ChAT and Ach expression in the hippocam-pal tissues(all P<0.05).Compared with the surgery group,the donepezil group exhibited a shortened escape latency,in-creased retention time,platform crossings,decreased AChE expression,and increased ChAT and Ach expression;the mice in the mu-p75-sap group showed a prolonged escape latency,decreased retention time and platform crossings,de-creased ChAT and Ach expression,and increased AChE expression in comparison with those of the surgery group(all P<0.05).Conclusions Hepatic lobectomy can affect postoperative cognitive function in mice.Central cholinergic neuron degeneration may exacerbate the impact on postoperative cognitive function,potentially leading to the development and pro-gression of postoperative cognitive impairment.

cholinergic neuron degenerationpostoperative cognitive functionhepatolobectomyacetylcholines-terasecholine acetyltransferaseacetylcholine

文进秋、郑敏、李新灵、阎晨、刘涛、王博、刘玉婷

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新疆医科大学第三临床医学院附属肿瘤医院麻醉科,乌鲁木齐 830000

胆碱能神经元变性 术后认知功能 肝叶切除术 乙酰胆碱酯酶 胆碱乙酰转移酶 乙酞胆碱

新疆维吾尔自治区自然科学基金

2022D01C791

2024

山东医药
山东卫生报刊社

山东医药

CSTPCD
影响因子:1.225
ISSN:1002-266X
年,卷(期):2024.64(8)
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