摘要
目的 探讨水通道蛋白4(AQP4)对大鼠脑缺血再灌注损伤的影响作用和寻找防治脑缺血再灌注损伤的新途径。 方法 采用自行构建的含 AQP4 基因的真核表达质粒,在大鼠脑内进行预先转染,观察分析转染后大鼠脑内AQP4表达水平的变化、卒中后 24 h脑梗死灶体积及大鼠卒中后神经功能缺损程度的变化。 结果 (1)单纯给予大鼠脑内注射 AQP4 基因 24 h后,大鼠的神经功能缺损评分无明显变化;(2)AQP4基因干预组大鼠缺血 2 h再灌注 12 h和 24 h神经功能缺损评分分别为(7 .9±0. 7)、(7. 1±0 .9)分,明显低于AQP4基因干预对照组;(3)注射含AQP4基因的真核表达质粒后可升高大鼠脑缺血再灌注损伤早期脑内 AQP4 的表达水平;(4) AQP4 基因干预组脑再灌注24 h皮质和纹状体梗死灶体积分别为(261 .0±18. 2) mm3、(21. 9±1 .9) mm3,明显大于AQP4基因干预对照组和对照组(P<0. 05)。 结论 (1)单纯提高脑内 AQP4 的水平并不影响大鼠神经功能;(2) 预先提高脑内AQP4的水平,可加重脑缺血再灌注损伤的程度;(3)改变脑内 AQP4水平或活性可望成为新的防治脑卒中后脑损伤的新策略。
Objective To investigate the effects of aquaporin4 (AQP4) on the brain injury after cerebral ischemic reperfusion and to search the new method that can prevent and cure the injury. Methods Locally injection of naked DNA ( pcNDA3.1/Zeo), which carries AQP4 gene and reporter gene green fluorescent protein(GFP), in the brain was performed 12 h before ischemic challenge to up-regulate the AQP4 expression. The expressed level of AQP4, the infarction size and neurological deficit scores were estimated in three groups. Results (1) Exogenous AQP4 expression in the brain did not affect the healthy rat neurological deficit score; (2) Rat neurological deficit scores were 7.9±0.7, and 7.1±0.9 respectively in 12 h and 24 h after reperfusion in AQP4 injected group, which were lower than that in plasmid control group when both groups were challenged with reperfusion after ischemia; (3) Expression of AQP4 in the brain was higher in AQP4 injected group than plasmid control group and control group in early stage after reperfusion; (4) Expression of exogenous AQP4 in the brain increased the cortex and striatum infarction size 24 h after reperfusion, which were (261.0±18.2) mm 3 and (21.9±1.9) mm 3, respectively, in AQP4 injected group more than plasmid control group. Conclusions (1) Increased local AQP4 expression in brain does not affect neurological function in the healthy rat; (2) Pre-expression of AQP4 increase infarction size and neuro-functional injury; (3) Modification of AQP4 activity and regulation of AQP4 expression level would be the new strategy for the prevention of cerebral edema and the reduction of cerebral injury after stroke.
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2005年第3期201-204,共4页
Chinese Journal of Geriatrics
