AngⅡ在脑缺血大鼠大脑皮质中的表达及依达拉奉对其干预的影响

Expression of angiotensinⅡin the cerebral cortex following cerebral ischemia and the intervention effect of edaravone in the adult rats

目的:研究大鼠局灶性脑缺血后AngⅡ在脑组织中的表达变化规律及应用自由基清除剂-依达拉奉干预治疗对脑组织中AngⅡ表达的影响,探讨脑缺血后脑内AngⅡ表达的生物学作用及依达拉奉对缺血性脑损伤的保护作用。方法:采用微创开颅法建立大鼠大脑中动脉闭塞(MCAO)模型,分为正常对照组、假手术组、脑缺血组和药物干预组。应用免疫组织化学及尼氏染色方法分别观察脑缺血后和依达拉奉干预后AngⅡ在脑内的表达和神经元的变化。结果:在缺血半暗区可见大量AngⅡ阳性细胞,以缺血后1周数目最多,且免疫阳性反应最强,与对照组相比有显著性差异(P<0.05);尼氏染色显示,缺血半暗区可见大量变性坏死神经元,其中以1周组数量最多,与对照组相比有统计学意义(P<0.05);经依达拉奉干预后半暗区AngⅡ阳性细胞数量、光密度值及变性坏死神经元数量明显减少,与对照组比较有统计学差异,以治疗后3 d最为显著(P<0.01)。结论:①大鼠局灶性脑缺血后缺血半暗区AngⅡ表达增强,可能与缺血后神经元的病理变化有一定联系;②脑损伤后,依达拉奉可能通过抑制AngⅡ的表达而减少神经元的坏死,发挥脑保护作用。

Objective： To observe the expressive changes of Ang I in the brain after ischemia and the effect of edaravone, a free radical scavenger, on the expression of AngⅡ following the focal cerebral ischemia in the rats, exploring the biological function of Ang Ⅱ and the protective effect of edaravone on the ischemic brain injury. Methods： The rat model of middle cerebral artery occlusion （MCAO） was established by minimal invasive craniotomy. The rats were divided into normal control groups, sham operation groups, cerebral ischemia groups and drug intervention groups. Immunohistochemistry and Nissl staining were respectively used to observe the expressive changes of Ang I and pathological changes of neurons in the brain after cerebral ischemia and edaravone treatment. Results： There were a large number of Ang II -pos- itive cells in the ischemic border （penumbra） zone. The largest number and optical density of Ang Ⅱ -positive ceils strikingly reached the peak at 1 w after ischemia, significantly different with the control groups （ P 〈 0.05 ）. Some neurons of degeneration and necrosis were observed in the penumbra zone by Nissl staining, peaked at lw after MCAO, showing sig- nificantly differences compared with the control groups （ P 〈 0.05 ）. The quantity and intensity of Ang I -positive cells and neurons of degeneration and necrosis in the ischemic penumbra decreased obviously after the edaravone treatment,lowest level at the 3 d group, showing significantly differences compared with the saline groups （ P 〈 0.05 ）. Conclu- sions： ①The expression of Ang II increased in the ischemic penumbra, which may be involved with neuronal damage after focal cerebral ischemia in rats; ②Edaravone may be exert protect effect by inhibiting the expression of Ang Ⅱ , and further decreasing neuronal damage following ischemia.