洋橄榄叶素HY1对LPS诱导小鼠神经炎症的作用及机制探讨

Effect and Possible Mechanism of Elaiophylin HY1 Against LPS-Induced Neuroinflammation

目的研究洋橄榄叶素HY1对脂多糖(LPS)诱导小鼠神经炎症的作用及机制。方法 BALB/c小鼠随机分为正常对照组、LPS模型组、LPS模型组+HY1 3 mg·kg^(-1)组、LPS模型组+HY1 10 mg·kg^(-1)组。HY1连续给药7 d, LPS模型组及HY1给药组腹腔注射LPS 5 mg·kg^(-1),LPS注射6 h后取脑皮层组织进行检测。ELISA检测小鼠脑皮层组织中白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、单核细胞趋化蛋白1(MCP-1)和细胞间黏附分子1(ICAM-1)的含量。Western blot检测炎症通路相关蛋白环氧合酶2(COX2)、高迁移率族蛋白B1(HMGB1)、髓样分化因子88(MyD88)的表达水平。结果与正常对照组比较,LPS模型组脑皮层组织中炎症因子及炎症通路相关蛋白IL-1β,IL-6,TNF-α,MCP-1,ICAM-1,COX2,HMGB1,MyD88的水平显著增高(所有P<0.01),HY1 3 mg·kg^(-1)及10 mg·kg^(-1)给药组可降低脑皮层组织的促炎细胞因子、趋化因子和黏附分子的释放,并下调炎症通路相关蛋白COX2、HMGB1、MyD88蛋白的表达。结论 HY1可改善LPS诱导的小鼠神经炎症,机制可能与下调炎症蛋白COX2,HMGB1和MyD88相关。

OBJECTIVE To investigate the anti-neuroinflammation effects of elaiophylin elaiophylin1(HY1) on cerebral cortex of LPS induced mice. METHODS BALB/c mice were randomly divided into control group, LPS model group, LPS+HY1 3,10 mg·kg-1 treatment group, and LPS+HY1 10 mg·kg-1 treatment group. After 7 d of administration, mice in LPS model group and HY1 treatment groups were injected with 5 mg·kg-1 LPS intraperitoneally and cerebral cortex tissues were obtained for the following detection after 6 h of LPS injection. The levels of IL-1β, IL-6, TNF-α, MCP-1 and ICAM-1 in cerebral cortex tissues were measured by ELISA;the expression of inflammatory pathway-related protein, including COX2, HMGB1 and MyD88 were detected by Western blot. RESULTS Compared with the control group, the levels of inflammatory related factors and proteins including IL-1β,IL-6,TNF-α, MCP-1, ICAM-1, COX2, HMGB1, and MyD88 in cortex tissues of LPS model group were significantly increased(all P<0.01), while HY1 administration could decrease the release of proinflammatory factors, chemokine and adhesion molecules, and downregulate the expression of inflammatory proteins, such as COX2, HMGB1 and MyD88. CONCLUSION HY1 can protect against neuroinflammation in the cerebral cortex tissue of LPS-injured mice and the mechanism may be related to downregulating of COX2, HMGB1 and MyD88 proteins.