摘要
目的研究血管加压素1a受体(V1aR)拮抗剂对脑出血(in tracerebra l hem orrhage,ICH)后水孔蛋白-4(aquaporin-4,AQP 4)表达及血脑屏障(BBB)通透性的影响。方法运用立体定向技术,尾动脉采血制作大鼠脑出血模型。模型制作成功后,治疗组侧脑室注射V1aR拮抗剂,对照组仅注射等量人工脑脊液。采用免疫组化技术对血肿周围组织AQP 4蛋白进行检测。通过检测渗出到脑血管外的伊文斯蓝(Evans B lue,EB)的含量来定量观察BBB的通透性。结果脑出血后6h尾壳核血肿周围组织AQP 4蛋白表达开始增高,在脑出血1d达高峰(P<0.01),持续到3d以后逐渐下降,到7d仍高于正常水平。而用V1aR拮抗剂脑室注射后,AQP 4蛋白表达在各时间点表达明显降低。BBB通透性在脑出血后6h开始升高,1d达高峰(P<0.01),3d后回落,侧脑室注入V1aR拮抗剂后,BBB通透性与对照组比较明显下降(P<0.05)。结论V1aR拮抗剂能抑制AQP 4蛋白的表达,保护BBB,减轻脑出血后脑水肿。
Objective To investigate the effects of V1a vasopressin receptor（V1aR）antaganist on the AQP4 protein expression and the roles of AQP4 protein in brain edema formation. Methods Intracerebral hemorrhage （ICH）models were established by injection of autologous caudate artery blood into the caudate nucleus. After successful surgery,in treated group,0. 1μg V1a R antagonist was injected into lateral cerebral ventricle. In control group,the rats received intracerebroventricular injection of the equivalent artificial CSF. Immunohistochemistry method was adopted to analyse the expression of AQP4 protein around the microvessels. The blood-brain barrier （BBB）permeability was evaluated quantitatively by measuring Evans blue dye extravasations. Results After experimental intracerebral hemorrhage, the AQP4 protein performed significantly enhanced level in the control group,especially on 1d and 3d after ICH（P〈0.01）. When the rats received V1aR antagonist treatment,AQP4 protein showed a lower expression than that in the control group（P〈0. 01 ）. The BBB permeability showed a significant decrease at every time point in the treated group comparing with the control group（P〈0.05）. Conclusion V1aR antagonists protect BBB and reduce brain edema in the perihematoma region after ICH by downregulating the expression of AQP4 protein.
出处
《中风与神经疾病杂志》
CAS
CSCD
北大核心
2006年第3期264-266,I0001,共4页
Journal of Apoplexy and Nervous Diseases
