全反式维甲酸对缺血再灌注大鼠血脑屏障通透性的影响

Effects of all-trans retinoic acid on blood-brain barrier permeability in rats with cerebral ischemia/reperfusion injury

摘要:

目的 探究全反式维甲酸对缺血再灌注大鼠血脑屏障通透性的影响。方法 将180只健康雄性大鼠完全随机分为假手术组(Sham),缺血再灌注组(I/R)和全反式维甲酸干预组(ATRA),每组60只,使用ZeaLonga法制作局灶性脑缺血再灌注模型。在维甲酸干预(30 mg/kg)后不同时间点(1 d、3 d、7 d)分别通过测定大鼠脑梗死体积、伊文思蓝(EB)含量、基质金属蛋白酶-9(MMP-9)的表达来观察大鼠血脑屏障通透性的变化。结果 缺血再灌注后脑梗死体积及EB含量均在1 d达高峰,之后逐渐下降,1 d及7 d时ATRA组脑梗死体积及EB含量均明显低于I/R组(P<0.05)。MMP-9的表达3 d达高峰,免疫组化法显示3 d和7 d时ATRA组低于I/R组(P<0.05),免疫印迹法显示1 d、3 d、7 d时ATRA组低于I/R组(P<0.05)。结论 全反式维甲酸可以减轻再灌注后血脑屏障的破坏。

Abstract:

Objective To explore the effects of all-trans retinoic acid (ATRA) on blood-brain barrier permeability in rats with cerebral ischemia/reperfusion (I/R) injury.Methods One hundred and eighty healthy male rats were randomly and equally divided into sham group, I/R group, and ATRA group. The rat model of focal cerebral I/R injury was established by Zea Longa's method. At 1 day, 3 day, and 7 day after intervention with ATRA (30 mg/kg), the volume of cerebral infarction, content of Evans blue (EB), and expression of matrix metalloproteinase-9 (MMP-9) were determined to evaluate the changes in blood-brain barrier permeability in rats.Results The volume of cerebral infarction and EB content reached a peak at 1 d after cerebral I/R, and gradually decreased afterwards. The volume of cerebral infarction and EB content were significantly lower in the ATRA group than in the I/R group at 1 day and 7 day (P<0.05). The expression of MMP-9 reached a peak at 3 d. Immunohistochemical analysis showed the ATRA group had significantly lower expression of MMP-9 than the I/R group at 3 d and 7 d (P<0.05), while Western blot demonstrated that the ATRA group had significantly lower expression of MMP-9 than the I/R group at each time point (P<0.05).Conclusions ATRA may reduce damages in blood-brain barrier after I/R.