PPARγ激动剂藁本内酯的中枢抗炎作用及机制研究  

The central anti-inflammatory effects and molecular mechanism of ligustilide,an agonist of PPARγ

作　　者：毛晓娜[1] 杜俊蓉[1] 旷喜[1] 李玲娇 王良芬[1] 

机构地区：[1]四川大学华西药学院,成都610041

出　　处：《中药药理与临床》2017年第1期26-30,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：藁本内酯调控缺血性脑卒中神经炎性的分子机制;国家自然科学基金项目(81072636)

摘　　要：目的:探讨PPARγ激动剂藁本内酯的中枢抗炎作用及其分子机制。方法:THP-1巨噬细胞分别经2.5μM、5μM、10μM的藁本内酯处理1h后用1ug/ml LPS刺激,1h后Western Blot检测细胞中p-p38蛋白表达水平;分别用PPARγsiRNA或阴性对照siRNA转染THP-1巨噬细胞,24h后加入10μM藁本内酯,1h后用1.0μg/ml LPS进行刺激。LPS处理24h后Real-time PCR检测PPARγmRNA水平;LPS处理48h后,Western Blot检测PPARγ、TLR4、p-NF-κB p65蛋白表达水平,ELISA法测定TNF-α和MCP-1的含量。结果:5μM、10μM藁本内酯均能降低p-p38的表达水平;10μM藁本内酯能够抑制THP-1巨噬细胞中LPS诱导的PPARγmRNA、PPARγ水平的降低及TLR4、p-p38、p-NF-κB p65、TNF-α、MCP-1水平的升高,而PPARγsiRNA的转染拮抗了藁本内酯的上述抗炎作用。结论:藁本内酯能够通过激动PPARγ抑制TLR4/NF-κB信号通路的活化从而发挥抗炎作用。Objective： The present study is to investigate the central anti-inflammatory effects and molecular mechanism of ligustilide,an agonist of PPARγ.Methods： The THP-1 macrophages cells were treated with 2.5μM,5μM,10μM ligustilide respectively for 1h,followed by stimulation with 1.0μg/ml LPS.1h after LPS treatment,p-p38 and p38 levels in cell lysate were determined by Western blot.The THP-1 macrophages cells were transfected with PPARγ siRNA or scrambled negative control siRNA.Twenty-four hours after transfection,the cells were treated with 10 μM ligustilide for 1 h,followed by stimulation with 1.0μg/ml LPS.24 h after LPS treatment,PPARγ mRNA levels in cell lysate were determined by Real-time PCR; 48 h after LPS treatment,the protein levels of PPARγ,TLR4,NF-κB p65 in cell lysate were determined by Western blot and the contents of TNF-α,MCP-1 in supernatants were measured by ELISA.Result： 5μM,10μM ligustilide can reduced LPS-induced increases in the proteins expression of p-p38; 10μM ligustilide reduced LPS-induced decreases in the PPARγ mRNA levels and PPARγ protein expression; 10μM ligustilide reduced LPS-induced increases in the proteins expression of TLR4,p-NF-κB p65 and the concentrations of TNF-α,MCP-1.But the anti-neuroinflammatory effects of ligustilide were effectively attenuated by PPARγ siRNA.Conclusion： ligustilide may prevent neuroinflammatory response via TLR4/NF-κB signaling inhibition in a PPARγ-dependent manner.

关 键 词：藁苯内酯 神经免疫炎症 PPARΓ TLR4/NF-κB 

分 类 号：R285[医药卫生—中药学]