C5a-C5aR在棕榈酸诱导的小胶质细胞炎症中的作用及机制  

Roles and mechanisms of complement 5a and complement 5a receptor in palmitic acid induced microglia inflammation

作　　者：刘艳[1] 徐三清 龙文君 卢慧玲[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院儿科,武汉430030

出　　处：《实用医学杂志》2018年第2期176-179,183,共5页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:81401277;81270949)

摘　　要：目的观察棕榈酸(PA)及C5a受体(C5a R)拮抗剂(PMX53)干预后小胶质细胞的炎性改变,探讨C5a-C5a R在PA诱导的小胶质细胞炎症中的作用及机制。方法取新生1日龄小鼠,分离脑组织,原代培养小胶质细胞并进行分离纯化及鉴定。纯化小胶质细胞随机分成:对照组、PA组、PA+PMX53组。分别应用QT-PCR、Western blot及ELISA法检测PA及PA+PMX53干预后小胶质细胞Iba-1蛋白、ERK1/2m RNA及蛋白、TNF-α表达变化。结果 PA干预后,Iba-1蛋白及TNF-α浓度较对照组明显升高(P<0.001);PA组ERK1/2 m RNA及p-ERK1/2蛋白表达较对照组明显升高(P=0.005 6),而ERK1/2蛋白与对照组无明显差异(P>0.05)。PA+PMX53干预组较PA组Iba-1蛋白、p-ERK1/2蛋白、ERK1/2 mRNA及TNF-α浓度表达有所下降(P<0.001);ERK1/2蛋白在各组比较差异无显著性。结论 PA可能通过C5a-C5a R激活ERK通路,诱发小胶质细胞炎症反应,C5a R拮抗剂在神经系统炎性损伤疾病中具有神经保护作用。Objective To observe the effect of complement 5a receptor （CSaR） antagonist （PMX53） and palmitic acid （PA） on the inflammatory reaction of microglia, and to investigate the roles and mechanisms of com- plement C5a -CSaR in PA induced microglia inflammation. Methods Microglia from one day old mice was collect- ed, purified and identified by primary culture and immunohistochemical staining, and then was randomly divided into three groups including PA group, PA＋PMX53 group and control group. The expressions of tumor necrosis factor-α （TNF-α）, Iba-1 and ERK1/2 were determined by ELISA, Western blot and QT-PCR. Results In PA group, the levels of Iba-1 and TNF-α were higher significantly than the control group （P 〈 0.001 ）. Similarly, the levels of ERK1/2 mRNA （P = 0.005 6） and p-ERK1/2 protein（P 〈 0.001 ）in the PA group were higher significantly than that in control group in spite of no difference in ERK1/2 protein in all groups. However, the levels of Iba-1, p- ERKI/2 protein, ERK1/2 mRNA and TNF-α in the PA ＋PMX53 group were significantly lower than that in the PA group（P 〈 0.001）, although there was no difference in ERK1/2 protein in all groups. Conclusions C5a receptor antagonist suppresses inflammatory reaction of microglia induced byPA, suggesting that C5a- CSaR-ERK may par- ticipate in the inflammation of microglia induced byPA. Therefore, C5a receptor antagonist may protect the brain tissues from inflammation-induced damage.

关 键 词：棕榈酸 C5A受体 小胶质细胞 炎症 

分 类 号：R741[医药卫生—神经病学与精神病学]