CAJ | 학술논문

目的探讨水通道蛋白4(aquaporins 4,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、12 h组、24 h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24 h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12 h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,24 h较明显.AQP4蛋白在1h开始降低,6h降至最低点,12 h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.
목적 탐토수통도단백4(aquaporins 4,AQP4)재조기창상성뇌수종조직중적표체여조직병리개변,이급여혈뇌병장(blood-brain barrier,BBB)결구파배적상관성. 방법 건강성년Wistar대서120지,제작뇌창상모형,안수궤수자표법분위가수술조화창상조,창상조우분위창상1h조、3h조、6h조、12 h조、24 h조5개아조,매조20지.분별측정뇌함수량,병리관찰뇌수종정황급BBB결구변화,면역조직화학급면역인적실험검측뇌조직IgG화AQP4표체. 결과 가수술조뇌조직결구정상,IgG염색음성,뇌함수량급AQP4표체미견이상.창상조적뇌함수량종창상6h후명현증가,지24 h최고;IgG종창상1h후즉명현증가지6h,지후유지고수평지24h.병리관찰현시,뇌창상후1h즉출현BBB파배,홍세포종혈관내루출,조직간극증관,정현혈관원성수종,병수시간연장이축점가중;창상후6h교명현.창상후3h개시출현세포내수종,효질세포포체증대,포장담염혹공포양변,선립체종창,역수시간연장이축점가중,재6h교위명현.창상후12 h제료상술량충수종병존지외,개시출현조직배사、염성세포침윤급소효질세포증생,24 h교명현.AQP4단백재1h개시강저,6h강지최저점,12 h개시회승,정“V”형변화. 결론 이BBB파배위특정적혈관원성수종시조기뇌창상적주요병리개변,계이출현세포내수종병존적혼합성수종,수시간연장량충수종축점가중.조기뇌창상시AQP4표체하조,이당세포내수종삼여시AQP4표체상조.
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 24hours; IgG expression showed significant increase at 1 hour postinjury,peaked at 6 hours postinjury 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 postinjury,which manifested as vasogenic brain edema.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 characterized by BBB disruption is the primary histopathological change in early-phase of brain trauma,followed by the coexistence with intracellular edema and aggravation of the two forms of edema over time.AQP4 expression is down-regulated in the vasogenic edema phase but highly expressed at phase of the intracellular edema.