生地大黄汤通过干预MMP-9对自发性高血压大鼠脑出血模型血脑屏障结构和功能的影响

Effects of Shengdi Dahuang Decoction on the structure and function of blood-brain barrier by intervening MMP-9 in spontaneous hypertension rats of intracerebral hemorrhage

目的:观察生地大黄汤通过干预基质金属蛋白酶-9(MMP-9)对自发性高血压大鼠(SHR)脑出血模型血脑屏障(BBB)结构和功能的影响。方法:采用自体血注入法制备SHR脑出血模型,分为假手术组、模型组和生地大黄汤组。生地大黄汤组灌胃生地大黄汤(18.51g·kg-1·d-1),假手术组和模型组灌胃等量纯水,1次/d,连续3d。术后第3天,Longa评分比较神经功能损伤,电镜观察BBB结构,伊文思蓝法观察BBB通透率,脑含水量检测脑水肿程度,Western Blot检测血肿周围组织MMP-9表达情况。结果:与假手术组比较,模型组大鼠神经功能损伤明显,BBB结构被破坏,EB通透率比、脑含水量、MMP-9表达显著上升(P<0.05);与模型组比较,生地大黄汤干预后,大鼠神经功能损伤减轻,BBB结构和功能改善,EB通透率比、脑含水量、MMP-9表达显著降低(P<0.05)。结论:生地大黄汤能够减轻脑出血大鼠神经功能损伤,下调MMP-9表达,改善BBB结构和功能,达到保护作用。

Objective:To observe the effects of Shengdi Dahuang Decoction(SDD)on the structure and function of blood-brain barrier(BBB)by intervening MMP-9 in spontaneous hypertension rats of intracerebral hemorrhage(ICH).Methods:The ICH model was established by method of autologous blood injection.Rats were randomly divided into 3 groups:sham group,ICH group and SDD group.Rats in SDD group were treated with SDD(18.51g·kg-1·d-1),and those in sham operation group and ICH group were given equivalent purified water once a day for three days.On the third day after operation,nerve function damage was compared by Longa score,structure of BBB was observed by transmission electron microscope and permeability of BBB was tested by Evans blue assay.Brain edema level was evaluated by brain water content and and expression of MMP-9 protein was detected by Western Blot assay.Results:Compared with sham group,rats of ICH group had bad nerve function,damaged BBB,and higher permeation ratio of EB,brain water content and the expression of MMP-9(P<0.05).After use of SDD,rats had lighter never function,improved structure and function of BBB,as well as lower expression of MMP-9 than ICH group(P<0.05).Conclusion:Shengdi Dahuang Decoction could alleviate nerve function damage,downregulate MMP-9 expression,improve structure and function of BBB and achieve the protective effect.