羟基红花黄色素A对大鼠局灶性脑缺血再灌注NMDAR_1蛋白表达的影响

目的　探讨羟基红花黄色素A(hydrosafflowyellowA ,HSYA)对大鼠局灶性脑缺血的保护作用及其机制。方法采用大鼠大脑中动脉闭塞 (MCAO)模型 ,观察HSYA对MCAO 2h ,再灌注 0、1、3、6、9、12、2 4及 72h ,1、2周时脑组织病理和NMDAR1 蛋白表达的变化。结果　HE染色显示缺血 2h再灌注 0～ 1h即可见神经细胞变性 ,细胞周围水肿 ,再灌注 3～ 6h可见软化灶。再灌注 12～ 2 4h ,软化灶扩大。治疗组可明显减轻缺血性损伤 ,神经细胞变性和坏死明显减轻。免疫组织化学染色可见NMDAR1 蛋白在正常大鼠大脑皮质锥体样细胞上呈散在阳性表达。缺血再灌注 0～ 1hNMDAR1 蛋白表达即明显增高 ,3h左右达高峰 ,然后逐渐下降 ,2 4～ 72h表达明显低于正常 ,1～ 2周时表达开始恢复 ,但仍偏低。与同时间点对照组比较 ,HSYA可明显降低早期 (12h以内 )NMDAR1 蛋白的表达 ,上调后期 (2 4h以后 )NMDAR1 蛋白的表达。结论　HSYA对缺血再灌注脑组织具有保护作用 ,其对NMDAR1 蛋白表达的双向调节作用可能为其脑保护作用的重要机制

The effect of hydrosafflower yellow A on the NMDA receptor 1 protein expression in rats with focal cerebral ischemia-reperfusion injury

Objective To study the cerebral protective effect and the mechanism of hydrosafflower yellow A (HSYA) in rats with focal ischemia-reperfusion.Methods The effect of HSYA on the pathological changes and expression of the NMDAR 1 after ischemia-reperfusion was observed in the rat model of MCAO.Results Under HE staining,the changes as follows could be seen:the neuron degeneration and edema could be seen in 0～1 h after reperfusion;some infarction could be seen in 3～6 h after reperfusion and the extent of infarction extended in 12～24 h after reperfusion;the degeneration and necrosis of neurons was obviously decreased and the infarction was also reduced in treatment groups. Under immunohistochemical staining, there was moderate NMDAR 1 positive expression in the cells like neurons in normal rats. The NMDAR 1 expression increased sharply after reperfusion for 0～1 h,and reached the peak in 3 h after reperfusion, then decreased gradually and showed an expression lower than normal in 24～72 h after reperfusion. The expression began to rise in 1～2 weeks but still lower than the normal level.In contrast to the control group, HSYA could largely reduce the NMDAR 1 expression in earlier stage (before 12 h) and increase the expression in later stage (after 24 h).Conclusion The HSYA has the protective effect on cerebral ischemia. The two-phase moderating effect of HSYA on the protein expression of NMDAR 1 after cerebral ischemia-reperfusion may be an important mechanism of cerebral protective effect.