丹红注射液对缺血性脑损伤大鼠海马CA1区醛糖还原酶表达的影响

Effect of Danhong Injection on Aldose Reductase Expression in Hippocampal CA1 Region of Ischemic Brain Injury Rats

关键词:  丹红注射液  脑缺血  醛糖还原酶

Key words:  Danhong injection  cerebral ischemia  aldose reductase

摘要:

目的 考察丹红注射液对脑缺血再灌注模型大鼠海马CA1区醛糖还原酶（aldose reductase，AR）表达的影响，并探讨其作用机制。方法 SD大鼠随机分为假手术组、缺血再灌注组（模型组）、缺血再灌注加丹红注射液组（丹红注射液组）、缺血再灌注加依帕司他组（依帕司他组），采用改良线栓法制作大脑中动脉缺血1 h再灌注模型，在大鼠脑缺血再灌注开始时丹红注射液组、依帕司他组分别按2 mL·kg^-1、20 μg·kg^-1在0，24，48 h尾静脉注射给药，72 h后处死大鼠取材。通过HE染色、免疫组化及Western blot等方法考察大鼠海马CA1区神经元细胞病理形态变化、AR的阳性细胞指数以及AR蛋白的表达变化。结果 给药72 h后，与假手术组相比，模型组大鼠脑组织海马CA1区神经元细胞凋亡较多，分布排列紊乱，且AR的阳性细胞数表达增多（P<0.05），Western blot显示AR表达量升高（P<0.05）。与模型组相比，丹红注射液组和依帕司他组神经元细胞凋亡减少，分布排列更整齐；丹红注射液组AR的阳性指数降低（P<0.05），且Western blot显示AR表达量降低（P<0.05）。结论 脑缺血再灌注损伤可激活大鼠海马CA1区AR的表达。丹红注射液对脑组织海马CA1区神经元细胞具有保护作用，其作用机制可能与降低AR的表达有关。

Abstract:

OBJECTIVE To investigate the effect of Danhong injection on aldose reductase(AR) expression in hippocampal CA1 of cerebral ischemia-reperfusion rats, and to reveal the protective mechanism. METHODS SD rats were randomly divided into sham operation group, ischemia-reperfusion group(model group), ischemia-reperfusion with Danhong injection group(Danhong injection group), ischemia-reperfusion with epalrestat group(epalrestat group). One hour reperfusion model of middle cerebral artery ischemia by modified suture method. At the beginning of cerebral ischemia-reperfusion in rats, the Danhong injection group and the epalrestat group were administered in travenously with dose of 2 mL·kg^-1, 20 μg·kg^-1 at 0, 24, 48 h. Then, the rats were sacrificed 72 h later. HE staining, immunohistochemistry and Western blot were used to evaluate the pathological changes of neurons, the AR positive index and expression level of AR in hippocampal CA1. RESULTS After 72 h of administration, compared with the sham group, the hippocampal CA1 displayed disordered neurons arrangement and significant apoptosis in the model group. Western blot showed that the expression of AR was significantly increased after cerebral ischemia-reperfusion(P<0.05). Compared with the model group, the Danhong injection group and epalrestat group exhibited less neuronal apoptosis and more regular neurons distribution. The AR positive index of Danhong injection group was decreased(P<0.05). Western blot showed that the expression of AR was also inhibited by Danhong injection. CONCLUSION Ischemia-reperfusion injury induced the expression of AR in hippocampal CA1. Danhong injection has protective effects on hippocampal CA1 neuronal cells via down-regulating the expression of AR.