不同程度慢性低度炎症对中枢神经炎症与认知功能影响的研究

Effects of different degrees of chronic low-grade inflammation on central nervous system inflammation and cognitivefunction

目的探讨不同程度慢性低度炎症对小鼠中枢神经炎症水平及认知功能的影响。方法雄性8周龄C57小鼠80只,随机分成假手术组(Sham组)、低浓度组(L组)、中浓度组(M组)及高浓度组(H组)。3组均连续6d腹腔注射脂多糖(LPS),LPS浓度分别为100μg/kg(L组)、200μg/kg(M组)及500μg/kg(H组),Sham组则连续6 d腹腔注射等量0.9%氯化钠注射液。采用酶联免疫吸附法检测小鼠血清及海马白介素-6(IL-6)、肿瘤坏死因子(TNF-α)水平,免疫荧光方法检测海马Iba-1水平,旷场及新物体识别实验检测认知行为学。结果与Sham组比较,L组、M组及H组外周IL-6、TNF-α及海马小胶质细胞活化水平显著升高(均P<0.05)。H组小鼠旷场中心区域活动时间显著减少(P<0.05),各组新物体识别实验结果差异无统计学意义(P>0.05)。结论小剂量LPS(100μg/kg)连续腹腔注射6 d即可导致成年小鼠中枢神经炎症,仅在大剂量时(500μg/kg)会诱发恐惧焦虑情绪,但视觉记忆能力无显著改变。

Objective To explore the effect of chronic low-grade inflammation of diferent degrees on the level of central nervous inflammation and cognitive function in mice.MethodsEighty male 8-week-old C57 mice were ran-domly divided into Sham group,low-concentration group(L group),medium-concentration group(M group)and high-concentration group(H group).The three groups were intraperitoneally injected with lipopolysaccharide(LPS,Escherichia coli 0111:B4)for six consecutive days,and the concentration ofLPS was 100μg/kg ofL grou,200μg/kg ofM group,500μg/kg ofGroup H,while the Sham group was intraperitoneally injected with the same amount ofLPS solvent(normal saline)for six consecutive days.Detection of interleukin-6(IL-6)and tumor necrosis factor(TNF)in serum and hippocampus by enzyme-linked immunosorbent assay.The level of Iba-1 in hippocampus was detected by immunofluorescence method.Cognitive behavior was tested by the open field and new object recognition experi-ments.Results Compared with Sham group,peripheral IL-6,TNF and the level of central Iba-lin L group,M group and H group increased significantly(all P<0.05).The activity time in the central area of the open field of mice in group H decreased significantly(P<0.05).There was no significant difference in the experimental results of new object recognition between the groups(P>0.05).Conclusions Low dose LPS(100μg/kg)continuous intraperito-neal injection for six days can cause central nervous inflammation in adult mice,and only in large doses(500μg/kg)can induce fear and anxiety,but there is no significant change in cognitive function.