摘要
目的研究高压氧预处理对老龄大鼠全脑缺血再灌注损伤时Nogo mRNA、Nogo-A及NgR蛋白表达的影响,探讨其改善认知功能的可能机制。方法雄性SD大鼠42只,月龄14月,随机分为4组:对照组(C组,n=6)、高压氧组(H组,n=12)、脑缺血再灌注损伤组(I/R组,n=12)和高压氧预处理组(HOP组,n=12)。H组和HOP组每天置于高压氧舱内1h,氧压为0.2MPa,连续5d,最后1次高压氧处理后24h时I/R组和HOP组采用改良Pulsinelli四血管闭塞法制备大鼠全脑缺血再灌注损伤模型,全脑缺血10min。再灌注24h时H组、I/R组和HOP组随机取6只大鼠断头取脑,分离大脑皮质,采用实时荧光定量PCR法检测Nogo mRNA的表达水平,Western blot法检测Nogo—A及NgR蛋白的表达水平。余大鼠自由喂养5d后采用Morris水迷宫实验测定认知功能。结果与C组比较,I/R组和HOP组认知功能降低,Nogo mRNA及Nogo-A蛋白表达上调(P〈0.05);与I/R组比较,H组和HOP组认知功能提高,Nogo mRNA及Nogo-A蛋白表达下调(P〈0.05)。各组NgR蛋白表达比较差异无统计学意义(P〉0.05)。结论高压氧预处理通过抑制脑皮质Nogo mRNA及Nogo—A蛋白表达上调,改善老龄大鼠全脑缺血再灌注损伤时的认知功能。
Objective To investigate the effect of hyperbaric oxygen preconditioning (HOP) on expression of Nogo mRNA, Nogo-A and NgR protein in the cerebral cortex after acute global cerebral ischemia-reperfusion (I/R) injury in aged rats. Methods Forty-two aged male SD rats aged 14 months weighing 480-530 g were randomly divided into 4 groups: group Ⅰ control (group C, n = 6) ; group Ⅱ HOP ( n = 12) ; group Ⅲ cerebral I/R ( n = 12) and group Ⅳ HOP + I/R ( n = 12). Global cerebral I/R was induced by 4-vessel occlusion method described by Pulsinelli. Bilateral vertebral arteries were permanently occluded by cauterization, and bilateral carotid arteries were occluded for 10 min. Successful induction of cerebral ischemia was confirmed by bilateral dilated pupils unresponsive to light and EEG changes. In group Ⅱ and Ⅳ the animals received 1 h hyperbaric oxyyen at 2 absolute atmospheric pressure per day for 5 consecutive days. In group Ⅳ (HOP + I/R) global cerebral I/R was induced at 24 h after last hyperbaric oxyyen treatment. Six animals in each group were killed at 24 h after I/R in each group and their brains were removed for detection of Nogo mRNA expression (by Q-PCR) and expression of Nogo-A and NgR protein (by Western blot) in cerebral cortex. Cognitive function was determined at 5 days after cerebral ischemia using Morris Water Maze in the other animals. Results The learning ability and memory were significantly decreased while the expression of Nogo mRNA and Nogo-A protein was significantly increased in group Ⅲ (I/R) and Ⅳ (HOP + I/R) as compared with control group. HOP significantly ameliorated the cerebral I/R-induced decrease in learning ability and memory and increase in Nogo mRNA and Nogo-A protein expression. Conclusion Hyperbaric oxyyen preconditioning can ameliorate acute global cerebral I/R injury- induced cognitive impairment by decreasing Nogo mRNA and Nogo-A protein expression in the brain.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2010年第2期223-226,共4页
Chinese Journal of Anesthesiology
基金
重庆市卫生局科研基金(渝卫科教2008-2-09)