米诺环素介导小胶质细胞形态转换减轻缺血性脑卒中早期脑损伤的机制研究

发布时间：2018-03-16 09:10

本文选题：米诺环素　切入点：缺血性脑卒中　出处：《第三军医大学学报》2017年11期 　论文类型：期刊论文

【摘要】：目的观察大鼠缺血性脑损伤早期的病理生理特点,探讨米诺环素在缺血性脑损伤早期的神经保护效应及可能机制。方法线栓法制备大鼠缺血性脑损伤(middle cerebral artery occlusion,MCAO)模型,在MCAO 6、24 h分别给予米诺环素腹腔注射,通过TTC染色观察脑梗死面积,TUNEL染色及尼氏染色检测神经元凋亡情况;免疫荧光染色了解小胶质细胞形态变化以及Western blot检测凋亡通路NF-κB表达情况。使用Morris水迷宫检测手术28 d后大鼠学习记忆能力。结果米诺环素减少MCAO 6 h后大鼠脑梗死面积[(43.0±5.3)cm~3vs(36.0±6.8)cm~3,P0.01],减少脑神经元凋亡数量并促进M2型(神经保护型)小胶质细胞增殖,MCAO 24 h后米诺环素治疗不能改善脑梗死以及神经元细胞凋亡(P0.05)。米诺环素显著减少MCAO 6 h诱导的凋亡信号通路蛋白NF-κB的表达(P0.01)。MCAO 28 d后大鼠学习记忆能力较假手术组显著降低;米诺环素显著改善MCAO后学习记忆能力(P0.05),而MCAO 24 h后米诺环素不能改善大鼠神经功能障碍,差异无统计学意义(P0.05)。结论米诺环素能促进缺血性脑卒中早期活化小胶质细胞向M2型转化并抑制凋亡信号通路,减轻脑缺血诱导的神经炎症及细胞凋亡,改善大鼠学习记忆功能。
[Abstract]:Objective to observe the early pathophysiological characteristics of ischemic brain injury in rats, and to explore the neuroprotective effect and possible mechanism of minocycline in the early stage of ischemic brain injury. Minocycline was injected intraperitoneally at 6h after MCAO for 24 h. The area of cerebral infarction was observed by TTC staining and Tunel staining and Nissl staining were used to detect neuronal apoptosis. The changes of microglia morphology and the expression of NF- 魏 B in apoptotic pathway were detected by Western blot with immunofluorescence staining. The learning and memory ability of rats after 28 days operation was measured by Morris water maze. Results minocycline decreased the brain of rats after MCAO 6 h. Infarct area [43.0 卤5.3 cm ~ 3 vs ~ 36.0 卤6.8 cm ~ (-1) P0.01]. Minocycline can not improve cerebral infarction and neuronal apoptosis P0.05. minocycline can not improve cerebral infarction and neuronal apoptosis P0.05. minocycline can not improve cerebral infarction and neuronal cell apoptosis after 24 hours of minocycline treatment by reducing the number of apoptotic neurons and promoting the proliferation of microglia of type M2 (neuroprotective type). The expression of NF- 魏 B in apoptotic signaling pathway protein (NF- 魏 B) induced at 6 h was significantly lower in rats than in sham-operated group after 28 days of P0.01U. MCAO. Minocycline significantly improved the ability of learning and memory after MCAO, while minocycline did not improve the neurological dysfunction of rats 24 h after MCAO. Conclusion Minocycline can promote the transformation of activated microglia to M2 type in the early stage of ischemic stroke and inhibit the signal pathway of apoptosis, alleviate the neuritis and apoptosis induced by cerebral ischemia, and improve the learning and memory function of rats.
【作者单位】：第三军医大学西南医院神经外科全军神经外科研究所全军神经系统疾病微创诊治专科中心全军神经创伤防治重点实验室;四川武警总队乐山医院神经外科;
【基金】：国家自然科学基金面上项目(81571116,81371440) 国家重点基础研究发展计划(973计划,2014CB541606)~~
【分类号】：R743.3

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