阿魏酸钠对脂多糖引起的大鼠海马炎症反应的抑制作用及其机制探讨  

Inhibitory effects and mechanisms of sodium ferulate on lipopolysaccharide induced inflammatory reaction in rat hippocampus in vivo

作　　者：闫恩志[1] 范莹[1] 隋海娟[1] 刘婉珠[2] 刘卓[1] 金英[1] 

机构地区：[1]辽宁医学院药理学教研室,辽宁锦州121001 [2]辽宁医学院机能实验中心,辽宁锦州121001

出　　处：《中成药》2013年第2期211-215,共5页Chinese Traditional Patent Medicine

基　　金：辽宁省教育厅创新团队项目(LT 2010064);辽宁省教育厅科学研究项目(L2012310)

摘　　要：目的研究阿魏酸钠抑制脂多糖所致大鼠海马炎症反应的信号传导机制。方法 SD大鼠随机分为对照组、模型组、阿魏酸钠组(100、200 mg/kg)。对照组、模型组大鼠灌胃等量生理盐水,阿魏酸钠组大鼠灌胃给予不同剂量阿魏酸钠(100、200 mg/kg)。3周后,模型组、阿魏酸钠组脑室注射脂多糖建立损伤模型,对照组注射等量生理盐水。取海马CA1区,Western蛋白印迹观察白介素-1β(IL-1β)、诱导型一氧化氮合酶(iNOS)、磷酸化丝裂原活化蛋白激酶3/6抗体(MKK3/MKK6)、磷酸化丝裂原活化蛋白激酶P38(p38MAPK)、磷酸化活化转录因子2(ATF-2)表达。RT-PCR检测IL-1β和iNOS的mRNA表达水平。结果阿魏酸钠(100、200 mg/kg)可对抗脑室内注射脂多糖引起的IL-1β、iNOS表达增加,抑制磷酸化的MKK3/6、p38MAPK和ATF-2表达(P<0.01)。结论阿魏酸钠通过抑制p38MAPK信号传导通路激活对抗脂多糖引起的海马炎症反应。ABSTRACT：lipopolysaccharide （LPS）-induced inflammatory reaction in rat hippocampus. METHODS SD rats were randomly divided into four groups ： control group, model group, sodium ferulate groups （ 100 and 200 mg/kg）. Rats were administered with sodium ferulate for 3 weeks in sodium fernlate groups and were administered with saline of the same volume in the control group and model group. Three weeks later, rats were injected intracerebroventricularly with LPS 5 μL （1.0 mmol/L） in the model group and sodium ferulate groups, and were injected with saline of the same volume in the control group. Western blotting was used to determine the expression of IL-1β, iNOS, phospho-mitogen-activated protein kinase kinase 3/6 （MKK3/MKK6）, phospho-mitogen-activated protein kinase p38 （p38MAPK）, phospho-activating transcription factor-2 （ATF-2）. RT-PCR was used to analyse the changes in IL-lβ mRNA and iNOS mRNA levels. RESULTS The experiment showed that sodium ferulate could antagonize the expression increase of IL-lβ and iNOS induced by intracerebroventricular injection of LPS in rats, and inhibit phosphorylated MKK3/MKK6, p38 MAPK, ATF-2 （P 〈 0. 01 ）. CONCLUSION Sodium fernlate, which may be related to its inhibitory effect on the expression of p38MAPK signal pathway, can improve the LPS-induced inflammatory response in rat hippocampus.

关 键 词：阿魏酸钠 脂多糖 丝裂原激活的蛋白激酶p38 海马 

分 类 号：R285.5[医药卫生—中药学]