中华临床医师杂志(电子版) 2017年2月,11卷4期

基础论著

抗炎治疗促进脑梗死后脑内神经发生和功能恢复的实验研究

吴晓巍1 孟庆敏2 张晓芳3 毛今明3 李常新1 李新果3

030001 太原,山西医科大学第一医院神经内科1;075000 河北张家口,河北北方学院附属第三医院神经内科2;030001 太原,山西医科大学第一临床医学院研究生3
李常新,Email: bananalcx@126.com

摘要:目的 探讨米诺环素对大脑中动脉闭塞(MCAO)大鼠的神经保护作用及潜在的促神经发生作用。方法 电凝法制备MCAO模型。实验大鼠随机分为假手术组、MCAO模型组及抗炎组后分别给予相应处理,于2周行转子杆、爬梯实验以及水迷宫测试评价运动及认知功能,并通过病理学处理及免疫组化检测对比各组各时间点梗死灶周5-溴脱氧核苷尿嘧啶(BrdU)、神经上皮干细胞蛋白(Nestin)、胶原纤维酸性蛋白(GFAP)阳性细胞计数。组间比较用单因素方差分析,两两比较用t检验。结果 与模型组相比,急性期米诺环素短期治疗并不能明显减小梗死面积,但运动功能、空间学习及记忆能力均有所恢复(P<0.05)。抗炎组BrdU、Nestin以及GFAP阳性细胞数较对照组增加(P<0.05),BrdU、GFAP阳性细胞呈增加趋势,2周时增加最为明显;Nestin阳性细胞1周达高峰,之后逐渐下降。结论 脑梗死急性期米诺环素治疗可能通过促进神经发生过程补偿、修复局部病灶的功能损伤与缺失,从而促进脑梗死大鼠神经功能恢复。

关键词:大脑中动脉闭塞; 神经前体细胞; 5-溴脱氧核苷尿嘧啶; 神经上皮干细胞蛋白; 胶原纤维酸性蛋白; 抗炎治疗

2012年度山西医科大学科技创新基金(C01201014)

Acute treatment with minocycline promotes neurogenesis and reduces functional impairment after focal cerebral ischemia

Wu Xiaowei1, Meng Qingmin2, Zhang Xiaofang3, Mao Jinming3, Li Changxin1, Li Xinguo3.

Department of Neurology, First Hospital of Shanxi Medical University, Taiyuan 030001, China; 2Department of Neurology, the Third Hospital of Hebei North University, Zhangjiakou 075000, China; 3Graduat
Li Changxin, Email: bananalcx@126.com

Abstract:Objective To investigate the neuroprotective and pro-neurogenesis effect of minocycline on experimental cerebral ischemic rats. Methods Middle cerebral artery occlusion (MCAO) rats model were prepared by electric coagulation. The rats were divided randomly into 3 groups as sham control group, MCAO group and anti-inflammatory group, and then underwent different management. 5-Bromodeoxyuridine (BrdU) was given to trace proliferation of neural precursor cells (NPCs). The number of preserved new neurons and astrocytes were marked by neuroepithelial stem cell protein (Nestin) and collagen fiber acid protein (GFAP), respectively. Motor function evaluation and cognitive tests were processed after 2 weeks' treatment. Results After 2 weeks' minocycline treatment, there was no identifiable reduction in infarction size of MCAO rats, but motor function, spatial learning and memory ability were resumed to a certain degree (P<0.05). In anti-inflammatory group, BrdU, Nestin and GFAP positive cells were increased significantly (P<0.05), GFAP and BrdU positive cells emerged a sustained growth trend in 2 weeks, while Nestin labeled cells reached the peak at 1 week, then decreased gradually. Conclusions Acute treatment with minocycline reduces functional impairment induced by focal cerebral ischemia. The potential mechanism might partly attribute to the inducement and/or facilitation of anti-inflammatory therapy to neurogenesis, which might due to the optimized micro-environment.

Keywords:Middle cerebral artery occlusion; Neurogenesis; BrdU; Nestin; Collagen fiber acid protein; Anti-inflammatory treatment

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(编辑:戚红丹 收稿日期:2016-10-17)