早期创伤性脑水肿水通道蛋白4的表达及组织病理改变  

Expression of aquaporins 4 and pathological changes in early phase of traumatic brain edema

作　　者：鲁宏[1] 雷小燕[1] 胡惠[1] 何占平[1] 

机构地区：[1]中南大学湘雅医学院附属海ISI医院,海口570208

出　　处：《中华创伤杂志》2013年第12期1224-1229,共6页Chinese Journal of Trauma

基　　金：国家自然科学基金资助项目（81160181）;海南省国际合作资助项目[琼科（2012）65号]

摘　　要：目的探讨水通道蛋白4（aquaporins4，AQP4）在早期创伤性脑水肿组织中的表达与组织病理改变，以及与血脑屏障（blood—brain barrier，BBB）结构破坏的相关性。方法健康成年Wistar大鼠120只，制作脑创伤模型，按随机数字表法分为假手术组和创伤组，创伤组又分为创伤1h组、3h组、6h组、12h组、24h组5个亚组，每组20只。分别测定脑含水量，病理观察脑水肿情况及BBB结构变化，免疫组织化学及免疫印迹实验检测脑组织IgG和AQP4表达。结果假手术组脑组织结构正常，IgG染色阴性，脑含水量及AQP4表达未见异常。创伤组的脑含水量从创伤6h后明显增加，至24h最高；IgG从创伤1h后即明显增加至6h，之后维持高水平至24h。病理观察显示，脑创伤后1h即出现BBB破坏，红细胞从血管内漏出，组织间隙增宽，呈现血管源性水肿，并随时间延长而逐渐加重；创伤后6h较明显。创伤后3h开始出现细胞内水肿，胶质细胞胞体增大，胞浆淡染或空泡样变，线粒体肿胀，亦随时间延长而逐渐加重，在6h较为明显。创伤后12h除了上述两种水肿并存之外，开始出现组织坏死、炎性细胞浸润及小胶质细胞增生，24h较明显。AQP4蛋白在1h开始降低，6h降至最低点，12h开始回升，呈“V”形变化。结论以BBB破坏为特征的血管源性水肿是早期脑创伤的主要病理改变，继而出现细胞内水肿并存的混合性水肿，随时间延长两种水肿逐渐加重。早期脑创伤时AQP4表达下调，而当细胞内水肿参与时AQP4表达上调。Objective To investigate the expression of aquaporins 4 （AQP4） and histopathological changes in early phase of traumatic brain edema and the correlation between AQP4 expression and structural damage to blood-brain barrier （BBB）. Methods A total of 120 healthy adult Wistar rats were divided into sham operation group and brain trauma group （ which was subgrouped at hours 1, 3, 6, 12 and 24 postinjury） according to random number table, with 20 rats per group. At each time point, brain water content was measured; brain edema and BBB structural changes were observed pathologically; IgG and AQP4 expressions in traumatic brain tissues were detected with immunohistochemical method and Western-blotting. Results In sham operation group, negatively stained IgG was observed and there were no abnormalities in brain tissue structure, brain water content as well as AQP4 expression. In brain trauma group, cerebral water content presented notable increase at 6 hours postinjury and peaked at 24 hours; IgG expression showed significant increase at 1 hour postinjury, peaked at 6 hours postiujury and remained a high level at 24 hours. Pathologic observation revealed damage to BBB, blood red cells leaking out of the blood vessels, and tissue gap widening at 1 hour postiniury, which manifested as vasogenic brainedema. Further, those phenomena were gradually aggravated over time and became obvious at 6 hours postinjury. Intracellular edema occurred at 3 hours postinjury, with the presence of increased glial cell body, cytoplasm light staining or vacuolar degeneration, as well as mitochondria swelling and was also aggravated with time, particularly at 6 hours postinjury. Except that the previously mentioned two forms of edema coexisted at 12 hours postinjury, tissue necrosis, inflammatory cell infiltration and microglia proliferation were emerged and aggravated at 24 hours postinjury. AQP4 level decreased at 1 hour, minimized at 6 hours and regained at 12 hours, showing a V-shape curve. Conclusions Vasogenic edema characteriz

关 键 词：脑水肿 病理学 水通道蛋白4 

分 类 号：R651.1[医药卫生—外科学]