摘要
目的:观察慢性低O2高CO2小鼠脑组织超微结构改变及神经炎症因子表达,探讨腺苷A2A受体与神经系统炎症的关系。方法:实验动物随机分为6组:对照野生组(NC+/+);对照杂合组(NC+/-);对照敲除组(NC-/-);低O2高CO24周野生组(4HH+/+);低O2高CO24周杂合组(4HH+/-);低O2高CO24周敲除组(4HH-/-)。利用野生型、A2A受体敲除型小鼠进行对照实验,电镜观察脑组织中神经胶质细胞改变以及外源性炎症细胞浸润;采用RT-PCR方法测定皮层和海马中TNF-αmRNA、IFN-γmRNA、TGF-β1mRNA的表达。结果:电镜示4HH+/+组比NC+/+组星形胶质细胞数量明显增加,形态以凋亡为主,同时可见足突明显水肿,少突胶质细胞水肿、空泡形成、髓鞘疏松;4HH-/-组比4HH+/+组凋亡的星形胶质细胞数量减少,形态仅轻度异常,未见明显水肿;实验动物脑内未见外周炎症细胞浸润。与相应小鼠表型的对照组比较,RT-PCR分析显示低O2高CO24周各组的皮层及海马的TNF-αmRNA、IFN-γmRNA表达上调(P<0.05);与4HH+/+组比较,4HH-/-组海马TNF-αmRNA表达上调不显著(P<0.05)。结论:慢性低O2高CO2小鼠脑组织存在程度不等的凋亡与炎症现象,腺苷A2A受体基因敲除可能通过抑制TNF-αmRNA表达等起到神经保护作用。
Objective： To examine the ultrastructural changes and expression of neuroinflammatory cytokines after exposure to chronic hypoxic hypercapnia, a mouse model of COPD, and to further investigate the effect of genetic inactivation of adenosine A2A receptor on these pathological changes. Methods= Mice were randomly divided into three control groups： the control wild-type group （NC＋/＋） ; control heterozygous knockout group （NC＋/-） ; control homozygous knockout group （NC-/-） and three hypoxic hypercapnia 4-week groups： hypoxic hypercapnia wild-type group （4HH＋/＋）; hypoxic hypercapnia heterozygous knockout group （4HH＋/-） and hypoxic hypercapnia homozygous knockout group （4HH-/-）. The uttrastructural changes in glias, the infiltration of exogenous inflanmatory cells in the brain of wild type and A2A receptor knockout mice were observed by electron microscope. The expression of TNF- αmRNA, IFN- y mRNA, TGF- β1 mRNA in cortex and hippocampus was determined by RT-PCR in these mice. Results： Compared with that in the NC＋/＋ group, the number of astrocytes with apoptotic characteristics was increased in the 4HH＋/＋ group, and edema of the foot process in astrocytes and edema.vacuolization in oligodendrocytes and rarefaction of myelin sheath were seen clearly. Interestingly, compared with the 4HH＋/＋ group, the 4HH-/- group had significantly less apoptotic astrocytes with reduced edema and mild morphological changes. However, there was no infiltration of peripheral inflammatory cells in every group. The expression of TNF- α mRNA, IFN-ymRNA in cortex and hippoeampus was significantly increased in three 4HH groups compared with their corresponding control groups by RT-PCR （P〈0.05）. Compared with the 4HH ＋/＋ group, the expression of TNF- α mRNA in hippocampus was increased unsignificantly in the 4HH-/- group （P〈0.05）. Conclusion： Inflammation and apoptosis in mice＇ s brain can be induced by chronic hypoxic hypercapnia. Adenosine A2A receptor knockout may be of protection after mice＇s exposure to chronic hypoxic hypercapnia by modulating neuroinflammation.
出处
《温州医学院学报》
CAS
2009年第2期119-123,共5页
Journal of Wenzhou Medical College
基金
浙江省自然科学基金资助项目基金号(Y2080503)
温州市科技局科研基金资助项目(Y2003A008)
