藏红花素联合左旋丁基苯酞对缺血性脑损伤大鼠的保护作用研究

Protective Effects of Saffron Combined with Levobutylphthalide on Ischemic Brain Injury in Rats

目的:探讨藏红花素联合左旋丁基苯酞对缺血性脑损伤大鼠的保护作用。方法:选取健康、清洁级Wistar雄性大鼠40只建立缺血性脑损伤模型,分为模型组、左旋丁基苯酞组、联合组和假手术组,每组10只。左旋丁基苯酞组大鼠给予左旋丁基苯酞40 mg/kg灌胃干预,联合组大鼠在左旋丁基苯酞组的基础上腹腔注射藏红花素40 mg/kg,假手术组和模型组大鼠给予等体积的0.9%氯化钠溶液干预。比较各组大鼠的神经功能、血脑屏障(BBB)通透性和脑组织含水量,观察脑组织病理学、神经细胞凋亡情况,检测脑组织氧化应激相关指标、勿动蛋白-66(Nogo-66)、勿动蛋白-66受体(NgR)和神经丝蛋白(NFP)的蛋白表达。结果:模型组、左旋丁基苯酞组和联合组大鼠的神经功能及超氧化物歧化酶(SOD)、过氧化氢酶(CAT)水平低于假手术组,BBB通透性、脑组织含水量、神经细胞凋亡数量和丙二醛(MDA)水平高于假手术组,差异均有统计学意义(P<0.05);左旋丁基苯酞组、联合组大鼠的神经功能及SOD、CAT水平高于模型组,BBB通透性、脑组织含水量、神经细胞凋亡数量和MDA水平低于模型组,差异均有统计学意义(P<0.05);联合组大鼠的神经功能及SOD、CAT水平高于左旋丁基苯酞组,BBB通透性、脑组织含水量、神经细胞凋亡数量和MDA水平低于左旋丁基苯酞组,差异均有统计学意义(P<0.05)。模型组、左旋丁基苯酞组和联合组大鼠NFP蛋白表达低于假手术组,Nogo-66、NgR蛋白表达高于假手术组;左旋丁基苯酞组、联合组大鼠的NFP蛋白表达高于模型组,Nogo-66、NgR蛋白表达低于模型组;联合组大鼠的NFP蛋白表达高于左旋丁基苯酞组,Nogo-66、NgR蛋白表达低于左旋丁基苯酞组,上述差异均有统计学意义(P<0.05)。结论:藏红花素联合左旋丁基苯酞灌胃能保护大鼠神经功能,减轻氧化应激损伤,其作用机制与调控Nogo-66、NgR和NFP蛋白有关。

OBJECTIVE:To probe into the protective effects of saffron combined with levobutylphthalide on ischemic brain injury in rats.METHODS:Forty healthy and clean Wistar male rats were selected to establish the ischemic brain injury model and divided into the model group,levobutylphthalide group,combined group and sham surgery group,with 10 cases in each group.Rats in the levobutylphthalide group were given 40 mg/kg gavage intervention,the combined group was intraperitoneally injected with 40 mg/kg saffron on the basis of the levobutylphthalide group,the sham surgery group and model group received equal volume of 0.9% sodium chloride solution intervention.Neurological function,blood brain barrier(BBB)permeability and brain tissue moisture capacity were compared.The brain histopathology and neural apoptosis were observed,and the brain tissue oxidative stress related indicators,Nogo-66,NgR and neurofilament protein(NFP)expression were detected.RESULTS:The neurological function,SOD and CAT levels of rats in the model group,levobutylphthalide group and combined group were lower than those in the sham surgery group,BBB permeability,brain tissue moisture capacity,number of neuronal apoptosis and MDA levels were higher than those in the sham surgery group,with statistically significant differences(P<0.05).The neurological function,SOD and CAT levels of levobutylphthalide group and combined group were higher than those of the model group,while BBB permeability,brain tissue moisture capacity,number of neuronal apoptosis and MDA levels were lower than those of the model group,the differences were statistically significant(P<0.05).The neurological function,SOD and CAT levels of the combined group were higher than those of the levobutylphthalide group,while BBB permeability,brain tissue moisture capacity,number of neuronal apoptosis and MDA levels were lower than those of the levobutylphthalide group,with statistically significant differences(P<0.05).The expression of NFP in the model group,levobutylphthalide group and combined group was lower than that in the sham surgery group,while the expression of Nogo-66 and NgR was higher than that in the sham surgery group;the expression of NFP in the levobutylphthalide group and combined group was higher than that in the model group,while the expression of Nogo-66 and NgR was lower than that in the model group;the expression of NFP in the combined group was higher than that in the levobutylphthalide group,and the expression of Nogo-66 and NgR was lower than that in the levobutylphthalide group,with statistically significant differences(P<0.05).CONCLUSIONS:Gastric administration of saffron combined with levobutylphthalide can protect the neurological function of rats and alleviate the oxidative stress injury,and the mechanism of action is related to the regulation of Nogo-66,NGR and NFP.