阿魏酸钠对脂多糖引起的大鼠海马损伤的保护作用的信号传导机制  

Effects of sodium ferulate on lipopolysaccharide-induced c-Jun N-terminal kinase signal pathway 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] 

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：《中国老年学杂志》2014年第1期144-146,共3页Chinese Journal of Gerontology

基　　金：辽宁省教育厅科学研究项目(No.L2012310)

摘　　要：目的研究阿魏酸钠(SF)对脂多糖(LPS)所致大鼠海马神经元损伤保护作用的信号传导机制。方法 SD大鼠灌胃给予SF(100,200 mg/kg)3 w后,脑室注射LPS建立损伤模型,对照组灌胃及注射等量生理盐水,Western蛋白印迹观察磷酸化丝裂原激活的蛋白激酶的激酶4(MKK4)、磷酸化c-Jun氨基末端激酶1(JNK1)、磷酸化c-Jun和caspase-3表达,应用荧光免疫组织化学进行p-JNK和OX-42双染,激光共聚焦显微镜观察磷酸化JNK的表达部位。结果与LPS损伤组比较SF(100,200 mg/kg)能对抗LPS引起的海马CA1区磷酸化MKK4、磷酸化JNK1和磷酸化c-Jun及caspase-3表达水平增加(P<0.05),激光共聚焦显微镜观察结果显示,磷酸化的JNK主要在小胶质细胞表达。结论 SF通过抑制JNK激酶信号传导通路的活化,对抗LPS引起的海马炎症反应。Objective To observe the neuroprotective mechanisms of sodium ferulate(SF) on lipopolysaccharide(LPS)-induced neurotoxicity in rat hippocampus.Methods Rats were injected intracerebroventricularly with LPS 5 μl(1.0 mmol / L).Rats in control group were injected with saline of the same volume.Six hours after injection,Western blotting was used to determine the expressions of p-MKK4,p-c-Jun,p-JNK1,and caspase-3 in hippocampal CA1 region.Immunohistochemistry and double labeling immunofluorescence combined with laser scanning confocal microscope were used to investigate the expression of p-JNK and OX-42 protein in hippocampal CA1 areas.Results Intracerebroventricular injection of LPS in rats induced significant increases in protein levels of p-MKK4,p-JNK1,p-c-Jun,and caspase-3.The LPS-induced changes could be reversed by SF(100 mg / kg and 200 mg / kg daily,3 weeks).The result of p-JNK and OX-42 expressions examined by double labeling immunofluorescence combined with laser scanning confocal microscope showed that most of p-JNK immunoreac- tivity co-localized with microglia-speccific protein OX-42.Conclusions SF prevents LPS-induced neurotoxicity through suppressing the ex- pression of phosphorylated JNK signal pathway in hippocampal CA1 region.

关 键 词：阿魏酸钠 阿尔茨海默症 脂多糖 C-JUN氨基末端激酶 细胞凋亡 

分 类 号：R749.16[医药卫生—神经病学与精神病学]