CART肽抑制缺血再灌注小鼠脑组织水通道蛋白4表达并减轻脑水肿  

CART peptide inhibits AQP-4 expression and alleviates brain edema in ischemia-reperfusion mice

作　　者：傅兴宁[1] 刘丽冰 张志杰[1] 师婷 祝世功[3] FU Xing-ning;LIU Li-bing;ZHANG Zhi-jie;SHI Ting;ZHU Shi-gong(Weifang Yidu Central Hospital,Oingzhou 262500,China;Fewang College of Shanxi Medical University,Fenyang032200,China;Peking University School of Basic Medical Science,Beijing 100191,China)

机构地区：[1]潍坊市益都中心医院,山东青州262500 [2]山西医科学大学汾阳学院,山西汾阳032200 [3]北京大学医学部基础医学院,北京100191

出　　处：《中国病理生理杂志》2018年第8期1363-1367,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81471254;No.81171081)

摘　　要：目的:研究可卡因及苯丙胺调节转录物(CART)肽对小鼠脑缺血再灌注急性期脑水肿的作用,并探讨其作用机制。方法:清洁级雄性ICR小鼠随机分为假手术(sham)组、大脑中动脉栓塞(MCAO)组和CART组,复制小鼠MCAO模型以模拟局灶性脑缺血再灌注损伤病理过程,TTC染色法计算脑梗死体积及脑水肿体积,干湿重法测定脑组织中水含量,通过检测伊文思蓝含量判断血脑屏障(BBB)的完整程度,免疫荧光和Western blot观察脑组织水通道蛋白4(AQP-4)的表达变化。结果:小鼠MCAO后24 h,CART肽处理组小鼠脑梗死体积和脑水肿体积均明显小于MCAO组(P<0.01),脑组织水含量亦明显低于MCAO组(P<0.01)。伊文思蓝测定表明,CART肽能够有效维持血脑屏障的完整性。免疫荧光和Western blot结果显示,MCAO小鼠脑组织中AQP-4表达明显升高,而CART处理明显抑制脑缺血再灌注诱导的AQP-4表达(P<0.05)。结论:CART肽可减轻脑缺血再灌注损伤小鼠急性期脑水肿,维持血脑屏障完整性,其作用机制可能与抑制脑组织AQP-4表达水平密切相关。AIM： To study the effect of cocaine-and amphetamine-regulated transcript（ CART） peptide on acute cerebral edema in mice after cerebral ischemia and reperfusion,and to explore its mechanism in this process.METHODS： The mouse model of middle cerebral artery occlusion（ MCAO） was used in this study. The brain infarct volume and swelling volume were measured by TTC staining. The water content in the brain tissue was calculated by dry and wet weight method. The integrity of the blood-brain barrier（ BBB） was determined by detecting the Evans blue leakage rate. Immunofluorescence and Western blot were used to observe the expression of aquaporin 4（ AQP-4） in the brain tissues. RESULTS： The cerebral infarction volume and edema volume in CART group were significantly smaller than those in MCAO group（ P〈0. 01）. The water content of the brain tissues in CART group was significantly lower than that in MCAO group（ P〈0. 01）. The results of Evans blue test showed that CART peptide effectively maintained the integrity of the BBB. Immunofluorescence observation and Western blot showed that the expression of AQP-4 was significantly increased in MCAO mouse brain tissues,while CART peptide treatment significantly inhibited the expression of AQP-4 induced by cerebral ischemia and reperfusion. CONCLUSION： CART peptide alleviates acute cerebral edema in the mice with cerebral ischemia-reperfusion injury,and maintains the integrity of BBB. This effect is closely related to the inhibition of AQP-4 expression.

关 键 词：可卡因及苯丙胺调节转录物 缺血再灌注损伤 水通道蛋白4 脑水肿 血脑屏障 

分 类 号：R743.3[医药卫生—神经病学与精神病学] R363[医药卫生—临床医学]