大黄提取物灌胃对脑梗死大鼠血脑屏障通透性的改善作用及其机制

Improvement and mechanism of Dahuang(rhubarb)extract on blood-brain barrier permeability in rats with cerebral infarction

目的观察大黄提取物灌胃对脑梗死大鼠血脑屏障(BBB)通透性的改善作用,并探讨其机制。方法180只SPF级SD雄性大鼠随机分为假手术组、模型组、大黄组,每组60只。模型组和大黄组大鼠采用经典longa's线拴法制备脑梗死模型。建模当日,大黄组大黄提取物灌胃,假手术组、模型组给予生理盐水灌胃,每天2次,连续观察,各组分别于观察的第1、3、5、7、10天随机抽取10只用于实验。采用Longa评分法对各组大鼠进行神经功能评分,采用甲酰胺浸泡法测算大鼠脑组织中伊文思蓝(EB)渗出量,采用Real-time PCR法检测各组大鼠脑梗死区Oc⁃cludin mRNA。结果建模后第1、3、5、7、10天,假手术组大鼠神经功能评分均为0分,模型组大鼠神经功能评分均高于假手术组(P均<0.05),大黄组大鼠神经功能评分均低于模型组(P均<0.05)。假手术组大鼠脑组织中EB渗出量较少,且各时间点无变化;模型组大鼠脑组织中EB渗出量均高于假手术组(P均<0.05),大黄组大鼠脑组织中EB渗出量均低于模型组(P均<0.05)。假手术组大鼠脑梗死区Occludin mRNA相对表达量在各时间点无明显变化趋势,模型组大鼠脑梗死区Occludin mRNA相对表达量均低于假手术组(P均<0.05),大黄组大鼠脑梗死区Occludin mRNA相对表达量均高于模型组(P均<0.05)。结论大黄提取物灌胃可改善脑梗死大鼠的BBB渗透性,其机制可能与大黄提取物阻止脑梗死区Occludin mRNA的降解有关。

Objective To observe the effect of Dahuang(rhubarb)extract in improving the permeability of the blood-brain barrier(BBB)in rats with cerebral infarction and to explore its mechanism.Methods Totally 180 specific pathogen-free(SPF)male SD rats were randomly divided into the sham operation group,model group,and rhubarb group,with 60 rats in each group.Rats in the model group and the rhubarb group were used to prepare cerebral infarction models by the classic longa's thread tethering method.On the day of modeling,the rhubarb extract in the rhubarb group was given intragastrically,and the rats in the sham operation group and the model group were given intragastric administration of nor⁃mal saline,twice a day for continuous observation.We randomly selected 10 rats in each group on the first,third,fifth,seventh,and tenth days of observation.The Longa scoring method was used to score the neurological function of each group of rats,the formamide soaking method was used to measure the amount of Evans blue(EB)exudation in the rat brain tissues,and the real-time PCR was used to detect the Occludin mRNA in the cerebral infarction area of rats in each group.Results On the 1,3,5,7,and 10 days after modeling,the neurological function scores of rats in the sham operation group were all 0 point.The neurological function scores of rats in the model group were higher than those in the sham opera⁃tion group,and the neurological function scores of rats in the sham operation group were lower than those in the model group(all P<0.05).The amount of EB exudation in the cerebral tissues of rats in the sham operation group was less,and there was no change at different time points;the amount of EB exudation in the brain tissues of the model group was higher than that in the sham operation group,and the amount of EB exudation in the brain tissues of the rhubarb group was lower than that in the model group(all P<0.05).The relative expression of Occludin mRNA in the cerebral infarction area of rats in the sham operation group did not change significantly at various time points.The relative expression of Occludin mRNA in the cerebral infarction area of rats in the model group was lower than that in the sham operation group(P<0.05),and the relative expression of Occludin mRNA in the cerebral infarction area of mice was higher in the rhubarb group than in the model group(all P<0.05).Conclusion Rhubarb extract can improve the BBB permeability of rats with cerebral infarction by intragastric administration,and the mechanism may be related to its prevention on the degradation of Occlu⁃din mRNA in the cerebral infarction area.