Change of aquaporin-4 in brain edema after cerebral ischemia reperfusion in rats
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摘要:
目的基于大鼠局灶性脑损伤缺血再灌注模型，观察水通道蛋白 4（AQP4）、蛋白激酶 C（PKC）的表达水平变化与脑水肿的关系。 方法线栓法复制大脑中动脉缺血再灌注模型，大鼠随机分为正常对照组、假手术组和缺血再灌注（CIR）组。通过绿色荧光蛋白 G FP 标识的 AQP4 示踪系统评价大鼠星形胶质细胞的水通透性，同时检测脑组织含水量和进行神经功能缺损评分。 AQP4 和 PKC 的表达使用免疫组织化学方法检测。 结果CIR 后 6 h 大鼠开始出现神经功能缺损，脑组织含水量在 CIR 12 h 明显升高，24 h~3 d 时达到高峰；AQP4 表达在早期水平降低，从 12 h 逐渐升高，至 CIR 24 h 明显升高，3 d 达高峰；PKC 在 CIR 6 h 后缓慢增加，连续 5 d 维持较高水平。 结论脑水肿可能和 PKC、AQP4 的升高相关，PKC 可能在 CIR 早期通过磷酸化 AQP4 以降低 AQP4 的表达以延缓脑水肿进程。 Abstract:ObjectiveTo explore the relationship between expression level of aquaporin-4 (AQP4), protein kinase C (PKC) and brain edema based on the focal cerebral ischemia reperfusion rat model. MethodsThe rat model of middle cerebral artery (MCA) was duplicated by suture method .The rats were randomly divided into normal control group, sham-operated group and cerebral ischemia reperfusion(CIR) group. Water permeability for rat astrocytes was evaluated by the green fluorescent protein(GFP) labeled AQP4 tracing system. Scores of neurofunctional defect were graded and water content in brain tissues was measured. Expression of AQP4 and PKC in brain tissue was detected by immunohistochemistry. ResultsNeurofunctional defect occurred at 6 h after CIR. Water content in brain tissue increased at 12 h after CIR, reached peak at day 1-3. The expression levels of AQP4 were decreased first, then increased gradually at 12 h later, obviously increased at 24 h after CIR and reached to highest point at day 3. While PKC increased gradually at 6 h after CIR, kept high level for 5 days. ConclusionBrain edema may relate to the rise of PKC and AQP4, PKC may reduce the expression of AQP4 via phosphorylation in the early stage of CIR in order to delay the process of brain edema. -
Key words:
- aquaporin4 /
- protein kinase C /
- water permeability /
- brain edema
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表 1 3组各观察指标的变化（x±s）
分组 例数（n） AQP4 PKC 脑含水量（%） 神经功能缺损评分 CIR组6 h 24 2.90±0.55* 5.49±0.53* 79.12±0.31 10.92±0.72* CIR组12 h 24 4.30±0.53 5.51±0.45* 80.16±0.21* 10.21±0.77* CIR组24 h 24 5.30±0.52* 5.95±0.81* 82.59±0.78* 9.19±2.16* CIR组3 d 24 6.30±0.53* 6.21±0.85* 82.87±0.56* 8.12±2.11* CIR组5 d 24 6.17±0.42* 6.42±0.53* 83.15±0.72* 10.29±1.11* 对照组 12 3.89±0.12 4.10±0.02 77.98±0.48 18.32±0.13 假手术组 12 3.62±0.53 3.65±0.59 77.69±0.53 17.65±0.54 F 21.5 32.4 18.3 85.7 P ＜0.05 ＜0.05 ＜0.05 ＜0.01 *P＜0.05 vs 对照组. 
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