贯叶连翘提取物对免疫性肝损伤小鼠肠道屏障功能损伤保护作用

The protective effect of Hypericum perforatum extract on intestinal barrier injury in acute immunological liver injury mice

目的 研究急性免疫性肝损伤对肠道屏障功能影响及贯叶连翘提取物（HPE）的作用。方法 60只ICR小鼠随机分为正常组、模型组、HPE低剂量组（25mg/kg）、HPE中剂量组（50mg/kg）、HPE高剂量组（100mg/kg）和地塞米松组（2.5mg/kg）。HPE组小鼠灌胃给予不同剂量HPE,连续10d后除正常组外小鼠禁食不禁饮,12h后采用尾静脉注射刀豆蛋白A（ConA）20mg/kg,8~12h后处死小鼠,取小肠组织,ELISA法测定肠匀浆二胺氧化酶（DAO）含量,免疫组化法测定肠组织闭锁蛋白（Occludin）、紧密连接相关蛋白-1（ZO-1）蛋白表达情况。结果 与正常组比较,模型组小鼠肠匀浆DAO水平明显降低,Occludin、ZO-1蛋白表达减弱,差异有统计学意义（P〈0.01）;与模型组比较,HPE各剂量组DAO水平显著升高,Occludin、ZO-1蛋白表达增强,差异有统计学意义（P〈0.01）。HPE高剂量组与HPE低剂量组比较,DAO、Occludin、ZO-1差异有统计学意义（P〈0.01）。结论 急性免疫性肝损伤时存在肠道屏障功能损伤,HPE对损伤的肠道屏障功能有保护作用,机制可能与增强Occlu-din、ZO-1蛋白表达有关。

Objective To investigate the protective effect of Hypericum petforatum extract （HPE） on intestinal bar- rier function in concanavalin A（ Con A） induced acute immunological liver injury mice. Methods Sixty ICR mice were randomly divided into six groups： normal group, model group, HPE（25,50,100 mg/kg） groups and dexam- ethasone group（2.5 mg/kg）. Different doses of HPE（25, 50, 100 mg/kg） were given to mice in HPE groups by gavage for 10 days. On day 10 Con A（20 mg/kg） was injected to mice by tail intravenous. After 8 to 12 h, mice were sacrificed. Diamine oxidase（DAO） levels in intestinal tissues were tested by ELISA assays. Expressions lev- els of Occludin, Zonula occludens-associated protein-1 （ ZO-1 ） were analyzed by immunohistochemical method. Re- sults Compared with the normal group, DAO levels and expressions levels of Occludin, ZO-1 were significantly decreased in the model group（P 〈 0. 01 ）. Compared with the model group, DAO levels and expressions levels of Occludin, ZO-1 were significantly increased in HPE group（ P 〈 0.01 ）. Compared with low dose group, DAO levels and expressions levels of Occludin, ZO-1 were significantly increased （ P 〈 0.01 ）. Conclusion Intestinal barrier function is damaged in acute immunological liver injury mice. HPE has obviously protective effects on the damaged intestinal barrier function, which may be associated with increasing expression of Occludin and ZO-1.