虾青素对db/db小鼠血脑屏障损伤和认知障碍的影响及机制  

Effect of astaxanthin on blood brain barrier injury and cognitive impairment in db/db mice and its mechanism

作　　者：李艳 高琳 刘耀武 周晓燕 LI Yan;GAO Lin;LIU Yao-wu;ZHOU Xiao-yan(Graduate School,Xuzhou Medical University,Xuzhou,Jiangsu 221000,China;Dept of Pharmacology,School of Pharmacy,Xuzhou Medical University,Xuzhou,Jiangsu 221000,China;Dept of Genetics,School of Life Sciences,Xuzhou Medical University,Xuzhou,Jiangsu 221000,China)

机构地区：[1]徐州医科大学研究生学院,江苏徐州221000 [2]徐州医科大学药学院药理学教研室,江苏徐州221000 [3]徐州医科大学生命科学学院遗传学教研室,江苏徐州221000

出　　处：《中国药理学通报》2023年第6期1073-1077,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金青年项目资助(No 81701298);徐州市推动科技创新专项资金项目资助(No KC21062)。

摘　　要：目的明确虾青素(astaxanthin,ASTA)对高血糖引起的血脑屏障(blood brain barrier,BBB)损伤和认知障碍的影响及机制。方法8周龄db/db雄性小鼠给予不同剂量(5、10、20 mg·kg^(-1))的ASTA灌胃,持续4周。Western blot检测小鼠脑部CD31,闭合小环蛋白-1(zonula occluden-1,ZO-1)和紧密连接蛋白5(claudin5,Cldn5)的蛋白表达,酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)检测脑部炎症因子白介素-6(interleukin-6,IL-6),白介素-1β(inter-leukin-1β,IL-1β)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的水平。水迷宫检测各组小鼠的学习记忆功能。结果db/db小鼠脑部CD31,ZO-1和Cldn5蛋白表达明显低于db/m小鼠,10和20 mg·kg^(-1) ASTA灌胃,能明显增加db/db小鼠脑部CD31,ZO-1和Cldn5蛋白的表达水平;db/db小鼠脑部炎症因子明显高于db/m,ASTA 10 mg·kg^(-1)灌胃能够减轻高血糖引起的糖尿病小鼠脑部的炎症反应;db/db小鼠的学习记忆功能明显低于db/m组,ASTA 10 mg·kg^(-1)灌胃能够改善db/db小鼠的认知功能。结论ASTA通过抑制脑部炎症因子的表达,缓解糖尿病引起的BBB损伤和认知障碍。Aim To investigate the effect of astaxanthin(ASTA)on the blood brain barrier(BBB)injury and cognitive disorders in mice induced by hyperglycemia and the possible mechanism.Methods db/db mice aged eight weeks were administered ASTA(5,10,20 mg·kg^(-1))by intragastric injection once daily for four weeks.After treatment,Western blot was used to detect the expressions of CD31,zonula occludens-1(ZO-1),and claudin 5(Cldn5)in brain of mic.Enzyme-linked immunosorbent assay(ELISA)was used to determine the level of interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNFα).The Morris water maze was used to detect mouse learning and memory function.Results After four weeks of ASTA(10 and 20 mg·kg-1)treatment,the expressions of CD31,ZO-1,and Cldn5 in brain tissues of db/db mice were significantly lower than those of db/m mice.The expressions of inflammatory cytokines in the brain of db/db mice were raised significantly compared with db/m mice,but the learning and memory functions in the db/db mice were worse than those of db/m mice.Furthermore,the results indicated that ASTA(10 mg·kg^(-1))could reduce the brain’s inflammatory response mediated by hyperglycemia and improve cognitive function.Conclusions ASTA inhibits the expression of inflammatory cytokines,and eventually alleviates the BBB injury and cognitive disorders induced by diabetes.

关 键 词：虾青素 糖尿病 血脑屏障 认知障碍 炎症 海马 

分 类 号：R-332[医药卫生] R322.81R338.64R364.5R587.1