阿尔茨海默病模型大鼠血浆内毒素激活小胶质细胞中P38和JNK及NF-κB作用的研究

The role of P38、JNK and NF-κB on activating MG by LPS in rats with Alzheimer disease

目的研究阿尔茨海默病(alzheimer disease,AD)模型大鼠脑组织P38、JNK、NF-κB在血浆内毒素(lipopolysaccharide,LPS)激活小胶质细胞(microglia,MG)中的作用。方法选用雄性Wistar大鼠,腹腔注射D-半乳糖和AlCl3,连续90d,制备AD大鼠模型。采用鲎试剂法检测模型大鼠血浆中LPS含量,免疫印迹法(western-blot)检测大鼠脑组织P38、JNK、NF-κB表达水平,免疫荧光法检测大鼠脑组织OX-42表达。采用SPSS 16.0软件分析,计量资料实验数据以均数±标准差(x±s)表示,用多因素重复测量方差分析及t检验进行两组间比较,P<0.05为差异有统计学意义。结果大鼠脑组织OX-42表达对照组与模型组均可见阳性荧光颗粒,荧光强度(767.2±35.4)vs(1 054.2±128.4),两组相比,t=2.534,P<0.01,差异有统计学意义。模型组与对照组大鼠脑组织P38、JNK蛋白各组均存在表达[(65.3±4.4)vs(684.9±6.1),(169.4±15.3)vs(183.2±17.5)],组间差异无统计学意义;而模型组大鼠脑组织p-P38、p-JNK表达水平明显高于对照组[64.3±5.8)vs(109.7±12.9),t=4.259,P<0.01;(21.9±2.8)vs(171.9±20.8),t=4.657,P<0.01]。模型组大鼠脑组织NF-κB表达水平(51.9±7.6)%明显高于对照组(34.7±4.6)%,两组相比差异有统计学意义(t=4.631,P<0.01)。结论 P38、JNK、NF-κB信号转导通路在AD模型大鼠血浆LPS激活MG进一步诱发AD过程中发挥了重要作用。

Objective To explore the role of P38、JNK and NF-κB on activating microglia by Lipopolysaccharide（LPS）in rats with Alzheimer disease（AD）.Methods Adult male Wistar rats were subjected to 90 days of consecutive intraperitoneal injection with D-galactose and aluminum trichloride（AlCl3） to establish the Alzheimer disease model.Rats in control group were injected with NS.After the administration,the serum level of LPS was measured by Tachypleus Amebocyte Lysate method and the expression of P38、JNK、NF-κB and OX-42 in the brain were determined by Western-blot and IFA.SPSS 16.0 software was used to analyze the data.Results Compared to the control group,the serum level of LPS and the expression of P38、JNK、NF-κB and OX-42 in the brain of AD rats were all significantly higher（P0.01）.Conclusions The P38、JNK and NF-κB play important roles on activating microglia by LPS in the AD rats model which were established by D-galactose and AlCl3.