LXR对新生小鼠炎症模型中脑中缝背核内5-HT表达的调节作用  

Activation of liver X receptor suppresses LPS-induced inflammation in the midbrain dorsal raphe nucleus of neonatal mice

作　　者：王颖[1] 高君伟[1] 赵敬会[1] 杨振慧[1] 范晓棠[1] 

机构地区：[1]第三军医大学组织胚胎学教研室,重庆400038

出　　处：《免疫学杂志》2015年第1期36-40,共5页Immunological Journal

基　　金：国家自然科学基金(31070927;81371197)

摘　　要：目的观察激活肝脏X受体对LPS致新生小鼠中脑中缝背核(dorsal raphe nucleus,DRN)内炎症反应的调节作用。方法采用小胶质细胞标记物(ionized calcium binding adapter molecule 1,Iba-1),5-hydroxytryptamine(5-HT)能神经元细胞标记物serotonin及tryptophan hydroxylase(TPH),运用免疫荧光方法检测LXR激动剂TO901317处理对出生后第12天LPS诱发的中脑DRN内小胶质细胞活化的影响及对5-HT能神经元的调节作用,采用ELISA法测定中脑内TNF-α的水平。结果新生小鼠LPS刺激可导致中脑DRN处Iba-1标记的小胶质细胞及serotonin、TPH标记的5-HT能神经元细胞数量显著增加(P<0.05,P<0.01,P<0.05),TO901317预处理能使LPS刺激新生小鼠中脑DRN处Iba-1标记小胶质细胞及Serotonin标记的5-HT能神经元细胞数量显著低于单纯LPS注射组(P<0.05,P<0.05),TNF-α在LPS组中脑的水平显著高于对照组和TO预处理组(P<0.05,P<0.05)。结论LXR受体激活能有效抑制中脑DRN处神经炎症反应,并抑制5-HT神经递质的分泌。To observe the inflammatory response in the midbrain dorsal raphe nucleus（DRN） of neonatal mice after activation of liver x receptor（LXR）, mice from the same batch at day 12（P12） were randomly divided into TO group treated with the liver X receptor agonist TO901317 and a control group treated with vehicle.Immunohistochemistry was done to detect the Iba-1 positive microglia, serotonin and tryptophan hydroxylase（TPH）positive neurons in the midbrain DRN. In addition, ELISA was also applied to observe the level of tumor necrosis factor α（TNF-α） from the midbrain tissue. Data showed that LPS treatment significantly increased the number of Iba1-positive microglia, serotonin-labeled neurons as well as TPH-positive 5-HT neurons in the DRN of LPS induced neonatal mice compared with control group（P〈0.05, P〈0.01, P〈0.05）. However, the number of Iba1-labeled microglia and serotonin-labeled 5-HT neurons were significantly reduced by TO901317 pretreatment（P〈0.05, P〈0.05）. Additionally, the expression of TNF-α was increased in the midbrain of LPS-induced mice in comparison with vehicle treated group, and TO901317 pre-treatment reduced LPS-induced release. In conclusion,activation of liver X receptor with TO901317 effectively inhibits the neuroinflammation in the midbrain DRN and decreases the release of 5-HT neurotransmitter.

关 键 词：LXR激动剂 中缝背核 小胶质细胞 5-HT能神经元细胞 

分 类 号：R392[医药卫生—免疫学]