大蒜素对脑出血大鼠血脑屏障通透性的影响及机制研究  

Effects and mechanism of allicin on the permeability of blood-brain barrier in rats with cerebral hemorrhage

作　　者：赵军苍[1] 郭宏盛 李永召 孙振宇 郝亚静 王献明[1] Zhao Juncang;Guo Hongsheng;Li Yongzhao;Sun Zhenyu;Hao Yajing;Wang Xianming(Department of Emergency Surgery,Handan Central Hospital,Handan 056001,China)

机构地区：[1]河北省邯郸市中心医院急诊外科,056001

出　　处：《心脑血管病防治》2021年第3期234-238,共5页CARDIO-CEREBROVASCULAR DISEASE PREVENTION AND TREATMENT

基　　金：邯郸市科学技术研究与发展计划项目(1823208039ZC)。

摘　　要：目的探讨大蒜素对脑出血大鼠血脑屏障通透性(BBB)的影响并探索其机制。方法180只Sprague-Dawley(SD)大鼠随机分为假手术组(0.9%氯化钠溶液),脑出血组(0.9%氯化钠溶液),大蒜素5、10、20 mg/(kg·d)组,尼莫地平2 mg/(kg·d)组,各30只。采用自体血注射法复制大鼠脑出血模型,造模成功后立即腹腔注射给药,每天1次,连续7 d。根据改良神经功能缺损评分标准(mNSS)评分以评价大鼠行为学,伊文思蓝渗透法测定BBB通透性,干湿比重法测定脑组织含水量,Western blot法检测闭合蛋白(Occludin)、紧密连接蛋白-5(Claudin-5)、闭锁连接蛋白-1(ZO-1)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)表达;酶联免疫吸附法检测肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)含量。结果与脑出血组比较,经大蒜素10、20 mg/(kg·d)或尼莫地平2 mg/(kg·d)治疗7d能够显著降低mNSS评分(t=6.655、11.298、8.895,P<0.01),降低脑出血大鼠脑组织渗透量和脑组织含水量(t=2.272~10.741,P<0.05),上调Occludin、Claudin-5、ZO-1蛋白表达(t=5.552~12.919,P<0.01),下调MMP-2和MMP-9蛋白表达(t=2.826、23.958,P<0.05),降低TNF-α、IL-6含量(t=2.234、8.401,P<0.05),IL-1β含量在大蒜素20 mg/(kg·d)组降低(t=2.975,P<0.01)。结论大蒜素对脑出血大鼠BBB通透性具有保护作用;可能与上调Occludin、Claudin-5、ZO-1表达,下调MMP-2、MMP-9表达以及抑制炎症反应有关。Objective To investigate the effects of allicin on the permeability of blood-brain barrier(BBB)in rats with cerebral hemorrhage and explore its mechanism.Methods 180 SD rats were randomly divided into sham operation group(0.9%sodium chloride solution),cerebral hemorrhage group(0.9%sodium chloride solution),allicin 5,10,20 mg/(kg·d)groups and nimodipine 2 mg/(kg·d)group,each had 30 rats.The model rats with cerebral hemorrhage were made by autogenous blood injection;the drugs were given by intraperitoneal injection immediately after successful modeling,once a day for 7 d.The behavioristics of the rats was evaluated by modified neureological severity scores(mNSS)scoring.The permeability of BBB was measured by Evans blue permeation method and the water content of brain tissue was measured by dry wet specific gravity method,the expression of brain tissue closure protein(Occludin),tight junction protein-5(claudin-5),locking Zonula Occluden-1(ZO-1),matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9)were determined by Western blot;the content of tumor necrosis factor-α(TNF-α),Interleukin-1β(IL-1β)and Interleukin-6(IL-6)were detected by enzyme linked immunosorbent assay.Results Compared with the cerebral hemorrhage group,the m NSS score of the rats in allicin 10,20 mg/(kg·d)and nimodipine 2 mg/(kg·d)group were decreased after 7 d of treatment(t=6.655,11.298,8.895;P<0.01),the permeability and the water content in brain tissue were reduced(t=2.272-10.741,P<0.05),the expression of Occludin,Claudin-5,ZO-1 were significantlyup-regulated(t=5.552-12.919,P<0.01),the MMP-2 and MMP-9 were significantly down-regulated(t=2.826-23.958,P<0.05);the content of TNF-αand IL-6 were decreased(t=2.234-8.401,P<0.05),the content of IL-1βin Allicin 20 mg/(kg·d)group was decreased(t=2.975,P<0.01).Conclusion Allicin has protective effect on the permeability of BBB in rats with cerebral hemorrhage,which mechanism may be related to the up-regulation of occludin,claudin-5 and ZO-1,downregulation of MMP-2,MMP-9 and inhibitio

关 键 词：大蒜素 脑出血 脑水肿 血脑屏障 炎症 

分 类 号：R285.5[医药卫生—中药学]