| 唐宇平,蔡定芳,刘军,陈依萍.大黄改善急性脑出血大鼠血脑屏障损伤的水通道蛋白-4机理研究[J].,2006,(2):152-156 |
| 大黄改善急性脑出血大鼠血脑屏障损伤的水通道蛋白-4机理研究 |
| Research on Acting Mechanism of Rhubarb on Aquaporin-4 in Rats with Blood-brain Barrier Injury after Acute Cerebral Hemorrhage |
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| DOI： |
| 中文关键词: 脑出血 水通道蛋白-4 血脑屏障 脑水肿 |
| 英文关键词:cerebral hemorrhage aquaporin-4 blood-brain barrier cerebral edema |
| 基金项目:上海百人项目(BR97016);国家自然科学基金资助项目(No.30271639) |
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| 中文摘要: |
| 目的探讨大黄改善急性脑出血血脑屏障损伤的水通道蛋白4(aquaporin4,AQP4)机理。方法采用立体定向注射自体无肝素动脉血制作大鼠脑出血模型,对神经功能缺损、脑含水量进行观察,伊文思蓝染色观察血脑屏障紧密连接(bloodbrainbarriertightjunction,BBBTJ)的损害,电镜观察不同时间点BBB和神经星形胶质细胞足突改变,用RTPCR和Westernblot检测AQP4mRNA和蛋白表达。结果脑出血后,与模型组比较,大黄可明显减轻脑水肿;伊文思蓝染色结果显示血脑屏障从12h开始明显损害;电镜结果提示出血后12h血脑屏障紧密连接被破坏,而且神经星形胶质细胞足突肿胀;大黄可有效使血脑屏障紧密连接的破坏减少、神经星形胶质细胞足突肿胀减轻。脑出血模型组大鼠AQP4表达出现增高(P<0.05);脑出血后1天AQP4mRNA和AQP4蛋白表达增强,第3天达峰值,其后逐渐有所下降。大黄可抑制AQP4基因转录和翻译。结论大黄可通过改善血脑屏障损伤减轻脑水肿;大黄改善血脑屏障破坏的作用可能是通过抑制AQP4基因转录和翻译实现的。 |
| 英文摘要: |
| Objective To investigate the mechanism of rhubarb in regulating aquaporin-4 in rats with blood-brain barrier damage after acute cerebral hemorrhage (CH). Methods CH model was induced by stereospecific injection of auto-blood into caudate nucleus of rats, and the brain water content and neurological defect were detected to evaluate cerebral edema and neurological defect level. Also, the blood-brain barrier damage was observed by Evan’s blue staining; the changes of blood-brain barrier tight junction and astrocyte end feet at different time points were observed with electron microscope; and the AQP-4 mRNA and protein expression were measured with RT-PCR and Western blot. Results Rhubarb showed effects in reducing cerebral edema. Evan’s blue result indicated the blood-brain barrier was evidently damaged at the 12th hour after CH, with blood-brain barrier tight junction damaged and astrocyte end feet process swelled obviously, but these changes could be relieved by rhubarb. The AQP-4 mRNA and protein expression in rats increased significantly 24 hrs after modeling (P<0.05) and reached the peak value at 72 hrs, and decreased gradually after then. Rhubarb also showed inhibiting transcription and translation of AQP-4 gene. Conclusion Rhubarb could alleviate cerebral edema via reducing blood-brain barrier tight junction damage and astrocyte end feet process swelling, which might be realized by the inhibition on transcription and translation of AQP-4 gene. |
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