缺血后适应调控树鼩脑缺血皮质TLR4表达  

Ischemia postconditioning regulates TLR4 expression in tree shrews's cortex of thrombotic cerebral ischemia

作　　者：冯蕊[1,2] 李树清[2] 

机构地区：[1]昆明医学院第一附属医院风湿免疫科,云南昆明650031 [2]昆明医学院基础医学院病理生理学教研室,云南昆明650031

出　　处：《基础医学与临床》2011年第5期503-508,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(30971171);教育部博士点专项基金(20050678008);云南省教育厅科研基金(09Y0154)

摘　　要：目的探讨缺血后适应对皮质髓过氧化物酶(MPO)、TLR4表达及炎性反应的影响。方法光化学法建立局灶性血栓性脑缺血模型;于脑缺血4 h后夹闭右颈总动脉5 min,再开夹5 min,共3个循环建立缺血后适应模型。HE染色观察脑皮质组织学改变及炎性反应,MPO免疫组化染色、Western blot法测定皮质TLR4蛋白表达,RT-PCR法测定皮质TLR4mRNA表达。结果缺血4、24和72 h后皮质神经元损伤及脑内炎性反应进行性加重,24 h达高峰,后适应处理后损伤明显减轻,且炎性细胞浸润减少。脑缺血后MPO表达增强,后适应后24及72 h表达减少(P<0.05)。脑缺血后TLR4蛋白表达升高(P<0.05),24 h达高峰,后适应后4及24 h表达减少(P<0.05),但后适应72 h表达增加(P<0.05)。TLR4mRNA的表达趋势与蛋白表达基本一致。结论缺血后适应的脑保护机制可能与调控TLR4表达及抑制脑内炎性反应有关。Objective To investigate the effect of postconditioning after brain ischemia on expresssion of MPO（myeloperoxidase）and TLR4（Toll-like receptor 4）and inflammation in cortex.Methods The thrombotic focal cerebral ischemia was induced by photochemical reaction in tree shrews,and ischemic postconditioning was established by repeated cycles of temporary right carotid artery clipped at 4 h after the onset of photochemical reaction and 5 min reperfusion.The change of histology of cortex（by Hematoxylin-and-Eosin）,MPO expression（by immunohistochemistry）,TLR4 expression（by Western blot） and TLR4 mRNA（by RT-PCR） were observed.Results Our study found extensive neuronal injury and inflammation in cortex at 4,24 and 72 h with peak at 24 h after cerebral ischemia,while the imjury was significantly attenuated after the postconditionng with less inflammation cells＇ infiltration.Immunohistochemistry analysis showed that cerebral ischemia caused an increase in MPO expression in cortex,and ischemic postcondionting decreased the expression at 24 h and 72 h（P0.05）.Cerebral ischemia caused an increase of the TLR4 expression in cortex（P0.05）,peak at 24 h.Postcondionting caused a decreaseof TLR4 expression in cortex at 4 hours and 24 hours（P0.05）followed by an increase at 72 hours（P0.05）.The levels of TLR4 mRNA in cortex showed the similar variation trend in accordance with the protein expression.Conclusion The protection mechanism of the prostconditioning may be related to inhibitting inflammation and regulating TLR4 expression.

关 键 词：光化学 炎性反应 脑缺血 Toll样受体4 缺血后适应 

分 类 号：R743.3[医药卫生—神经病学与精神病学]