吴茱萸碱抑制M2型巨噬细胞功能的机制研究  

Mechanisms of Evodiamine Attenuating M2 Polarized Macrophages

作　　者：樊垒垒 朱飞云[1,2,3] 崔琳[1,2] 王小晓[1,2] 张松江[3] 沈思[1,2] 朱明军[1,2] 王幼平[1,2] 

机构地区：[1]河南中医学院第一附属医院中心实验室,郑州450000 [2]河南中医学院第一附属医院心脏中心,郑州450000 [3]河南中医学院第一临床医学院,郑州450008

出　　处：《世界科学技术-中医药现代化》2015年第11期2322-2327,共6页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委面上项目(81170243);国家自然科学基金委项目:TRPV1受体在盐敏感性高血压过程中所介导的肾脏保护作用的机理研究;负责人:王幼平;河南省科技创新杰出人才项目(124200510007);河南省科技创新杰出人才项目:盐敏感性高血压过程中TRPV1受体调控单核/巨噬细胞功能的机理研究;负责人:王幼平

摘　　要：目的:吴茱萸碱是中药吴茱萸重要生物碱成分之一,其具有明显的抗炎作用,但具体机制不清。研究显示瞬时受体电位香草醛亚型1受体(Transient Receptor Potential Vanilloid Type 1 Channel,TRPV1)对炎症反应具有明显的抑制作用,而吴茱萸碱可激活TRPV1受体。本研究以人单核细胞(THP-1)培养模型,探明吴茱萸碱对M2型巨噬细胞功能的影响及TRPV1受体参与该过程中的作用,从而阐明吴茱萸碱抑制炎症反应的分子生物机制。方法:在THP-1细胞培养模型上,观察吴茱萸碱对白介素-4(Interleukin-4,IL-4)诱导的M2型巨噬细胞功能的影响,以及特异性TRPV1受体拮抗剂Capsazepine(CAPZ)对该过程的影响,并分别利用ELISA、荧光定量PCR和western blot确定M2型巨噬细胞功能指标,其中包括TGF-β1的产生、Arginase-1和Mannose Receptor m RNA和蛋白的表达。结果:本研究发现吴茱萸碱明显抑制IL-4诱导的M2型巨噬细胞功能亚型,其主要表现为TGF-β1分泌产生下降(P<0.05),同时伴有Arginase-1和Mannose Receptor m RNA和蛋白表达的降低(P<0.05),以上结果可被特异性TRPV1受体拮抗剂CAPZ所阻断(P<0.05)。结论:本研究显示吴茱萸碱通过激活TRPV1受体抑制M2型巨噬细胞功能反应,从而实现其抑制炎症反应的作用。Evodiamine（EVO） was one of the important alkaloids extracted from Chinese herb Evodia rutaecarpa which possessed the ability of anti-inflammation. However, the mechanisms responsible for its anti-inflammation remained to be elucidated. Several studies had shown that the transient receptor potential vanilloid type 1 channel（TRPV1） had obvious inhibitory effects on inflammatory response; and EVO activated TRPV1. This study cultured THP-1 model for the exploration on effect of EVO on M2 polarized macrophages as well as the role of TRPV1, in order to illustrate the molecular biological mechanisms of anti-inflammation effect by EVO. Based on the THP-1 cell culture model, the observation was made on influence of EVO to interleukin-4（IL-4） induced M2 polarized macrophage, as well as the specific TRPV1 antagonist Capsazepine（CAPZ）. Functional indexes of M2 polarized macrophage were identified by ELISA, fluorescence quantitative PCR and western blot, which included TGF-β1 production, the expression of arginase-1, mannose receptor m RNA and protein. The results showed that EVO obviously inhibited the levels of IL-4-triggered M2 polarized macrophage functional subtype, which was mainly manifested as decreased production of TGF-β1（P〈0.05）. Meanwhile, the expressions of arginase-1, mannose receptor m RNA and protein were decreased（P〈0.05）. All results mentioned above can be blocked by TRPV1 antagonist CAPZ（P〈0.05）. It was concluded that the inhibitory effects of EVO on M2 polarized macrophages appeared attributable to its ability to activate TRPV1 in order to realize its anti-inflammation effect.

关 键 词：吴茱萸碱 瞬时受体电位香草醛亚型1受体 M2型巨噬细胞 炎症 

分 类 号：R285[医药卫生—中药学]