毛蕊异黄酮对大鼠蛛网膜下腔出血后血脑屏障和氧化应激反应的影响

Effect of Calycosin on Blood-Brain Barrier Integrity and Oxidative Stress after Subarachnoid Hemorrhage in Rats

目的探讨毛蕊异黄酮对蛛网膜下腔出血脑水肿和神经炎症反应的影响。方法体质量230~250 g的雄性SD大鼠72只,随机分为4组:假手术对照组(Sham组)、蛛网膜下腔出血组(SAH组)、毛蕊异黄酮15(C1组)、30 mg/(kg·d)组(C2组)。采用血管内穿刺法建立大鼠蛛网膜下腔出血(SAH)模型。Sham组仅在手术操作中将尼龙线头端送至右颈内动脉,但不刺破动脉管壁;SAH组大鼠制备SAH模型;C1组和C2组大鼠分别每日口饲毛蕊异黄酮溶液(溶于无菌生理盐水)15或30 mg/kg共7 d,之后制备SAH模型。术后24 h行脑水含量检测和伊文思蓝染色以分别反映脑水肿和血脑屏障破坏程度;采用超氧化物歧化酶(SOD)和丙二醛(MDA)试剂盒分别检测脑SOD活性和MDA摩尔浓度。结果与Sham组比较,SAH组大鼠脑水含量和伊文思蓝外渗率均明显增加(P <0.05),SOD活性显著降低(P <0.05),MDA摩尔浓度明显增加(P <0.05);与SAH组比较,C1和C2组大鼠脑水含量和伊文思蓝外渗率均明显减少(P <0.05),SOD活性显著增加(P <0.05),MDA摩尔浓度下调(P <0.05)。结论毛蕊异黄酮预处理可缓解蛛网膜下腔出血后脑水肿和血脑屏障破坏,减轻神经炎症反应和细胞凋亡,其机制可能与激活Nrf2信号通路相关。

Objective To investigate the effect of calycosin on blood–brain barrier integrity and oxidative stress after subarachnoid hemorrhage in rats.Methods A total of 72 male Sprague-Dawley rats weighing 230-250 g were randomly divided into 4 groups:sham-operated control group(Sham group),subarachnoid hemorrhage group(SAH group),calycosin 15 mg/kg/day group(C1 group),calycosin 30 mg/kg/day group(C2 group).The endovascular perforation model of SAH in rats was used in the present study.In the Sham group,the tip of nylon filament was merely sent to the right internal carotid artery without puncture of the artery wall;the SAH model was prepared in the SAH group;the calycosin solution was administered daily in the C1 group(15 mg/kg/d)and the C2 group(30 mg/kg/d)for 7 days,followed by establishment of the SAH model.The brain water content and Evans blue extravasation was detected 24 h after the surgery to evaluate the extent of brain edema and blood-brain barrier disruption;The commercial kits for superoxide dismutase(SOD)and malondialdehyde(MDA)were used to detect the SOD activity and MDA content in the brain.Results Compared with the Sham group,the brain water content and Evans blue extravasation rate in the SAH group were significantly increased,the SOD activity was diminished,and the MDA content was significantly increased.Compared with the SAH group,the brain water content and Evans blue extravasation rate of the SAH group were reduced,the SOD activity was increased,the MDA content was significantly down-regulated.Conclusions The treatment of calycosin could relieve blood-brain barrier destruction and reduce oxidative stress in the brain after subarachnoid hemorrhage.