实验性脑出血后水通道蛋白-4的表达变化

目的　研究出血性脑水肿病理过程中水通道蛋白 4 (aquaporin 4 ,AQP4 )的表达与脑水肿形成之间的关系。方法　采用胶原酶制作大鼠脑出血模型 ,原位杂交和免疫组化法检测AQP4mRNA和蛋白质的表达变化 ,并用电镜技术和微血管灌注法观察脑水肿区的超微结构和微血管的变化。结果　与对照组相比 ,脑出血后 6h ,AQP4mRNA和蛋白质在脑水肿区表达增强 ,AQP4mRNA(吸光度值 ,A)由 0 2 9上升到 0 5 7(P <0 0 1) ,AQP4蛋白A值由 0 0 6上升到 0 15 (P <0 0 1) ,电镜下可见脑组织轻度水肿 ;至 72h ,AQP4mRNA和蛋白质的表达达到高峰 ,AQP4mRNA的A值为 0 88,AQP4蛋白A值为 0 2 5 ,此时脑组织严重水肿 ,神经元、胶质细胞和内皮细胞明显肿胀 ,毛细血管造影可见毛细血管开始增生 ;第 7天 ,AQP4的表达已减少 (尤以mRNA明显 ) ,但仍显著高于对照组 ,此时脑水肿已减轻。在整个脑水肿的形成过程中 ,AQP4mRNA和蛋白的表达呈高度正相关 (rs>0 82 ,Ps<0 0 1)。结论　脑出血后AQP4表达明显增强 ,提示AQP4参与了出血性脑水肿的发生发展过程 ,在出血性脑水肿的形成过程中起重要作用。

Changes of aquaporin-4 expressions in experimental rats after intracerebral hemorrhage

Objective To study the relationship between the expression of aquaporin-4 (AQP4) and cerebral edema formation during the pathologic course of hemorrhagic cerebral edema. Methods The intracerebral hemorrhage (ICH) was established by infusing collagenase into rat caudate nucleus. In situ hybridization and immunohistochemistry were respectively used to evaluate AQP4 mRNA and protein expression, and electronic microscopy and microangium perfusion were respectively used to observe the changes of the ultrastructural and local capillaries in perihematomal brain edema. Results As compared with the control group, there appeared a significant increase in AQP4 mRNA and protein expression on the edematous tissue at 6 hours in rats following ICH. AQP4 mRNA expression (optical density, A) was increased from 0.29 to 0.57 (P<0.01), and AQP4 protein expression (A) increased from 0.06 to 0.15. At the same time, the light swelling in perihematomal brain tissue was found. At 72 h, the expression of AQP4 mRNA and protein reached at its maximum, AQP4 mRNA expression (A) reached at 0.88 and AQP4 protein expression (A) at 0.25 (P<0.01). The brain edema became remarkable; neurons and glias together with endothelial cells were all remarkably swelling and capillaries began to proliferate in perihematomal tissue. At day 7, the expression of AQP4 mRNA and protein in intracerebral hemorrhagic group were still higher than that in the control group, and the brain edema was not remarkable. The AQP4 mRNA expression showed a positive relationship with the AQP4 protein expression during the brain edema formation (r s>0.82, P s<0.01). Conclusions The increased expression of AQP4 was participated in the course of ICH after hemorrhagic cerebral edema, suggesting that AQP4 should play an important role in the pathological course of the hemorrhagic cerebral edema.