一种新型α-MSH相关肽JYM595的抗炎活性研究  

Study on anti-inflammatory activity of a novelα-MSH related peptide JYM595

作　　者：林艳霞 倪穗颖 张利香 陈健文[2] LIN Yan-xia;NI Sui-ying;ZHANG Li-xiang(Shenzhen YJMed technology co.,Ltd,Shenzhen,Guangdong 518188,China)

机构地区：[1]深圳市健元医药科技有限公司,广东深圳518188 [2]中山大学药学院,广州510006

出　　处：《中国处方药》2020年第8期4-7,共4页Journal of China Prescription Drug

摘　　要：目的 研究一种以内源性多肽 α-MSH作为母体进行设计得到的新型多肽JYM595的体内外抗炎作用.方法 采用CCK-8法检测JYM595对RAW 264.7细胞活力的影响,选取合适浓度进行体外抗炎活性研究.以LPS刺激巨噬细胞RAW 264.7,ELISA试剂盒检测JYM595对RAW 264.7分泌炎症因子TNF-α、IL-6的影响.采用二甲苯诱导小鼠耳肿胀模型和角叉菜胶诱导大鼠足肿胀模型对JYM595的体内抗炎活性进行研究.结果 0.1~100 nM的JYM595对RAW 264.7的细胞活力无显著影响.选取0.1、1、10 nM的JYM595预处理RAW 264.71h后,用LPS刺激6 h,JYM595能浓度依赖性地抑制炎症因子TNF-α、IL-6的分泌,且同等浓度(1 nM)下,JYM595的抑制效果较 α-MSH好.腹腔注射给予小鼠0.1、0.25、0.5 mg/kg的JYM595能降低二甲苯诱导的耳肿胀程度,且呈剂量依赖性,0.25 mg/kg的JYM595与0.25 mg/kg的 α-MSH作用相当.在角叉菜胶诱导的大鼠足肿胀模型上,0.05、0.1、0.2 mg/kg JYM595能剂量依赖性地降低大鼠足肿胀程度.结论 JYM595具有体内外抗炎活性,在抗炎领域具有良好的开发前景.Objective To investigate the in vitro and in vivo anti-inflammatory effects of a novel petide(JYM595),which was obtained by a rational design based on the sequence of an endogenous peptideα-MSH.Methods The impact of JYM595 on RAW 264.7 viability were detected with CCK-8 assay and the concentration of JYM595 employed in the following in vitro study were chosen according to the result.A murine macrophage cell line RAW264.7 were stimulated with LPS and the effect of JYM595 on pro-inflammatory cytokines TNF-αand IL-6 production in RAW264.7 were tested with ELISA method.A dimethylbenzene-induced ear edema model in mice and a Carrageenan-induced paw edema model in SD Rat were established to study the in vivo anti-inflammatory activity of JYM595.Results At the concentration from 0.1 to 100 nM,JYM595 had no significant impact on RAW 264.7 cell viability.Pretreatment of 0.1,1 and 10 nM JYM595 for 1 h inhibited TNF-αand IL-6 production in RAW 264.7 cells stimulated with LPS for 6 h.At the concentrations of 1 nM,JYM595 exerted a more pronounced suppression effect thanα-MSH.Intraperitoneal injection of 0.1,0.25,0.5 mg/kg JYM595 caused dose-related suppression of ear edema induced in mice by dimethylbenzene.JYM595 andα-MSH were equipotent when given 0.25 mg/kg per mouse.In another in vivo model,0.05,0.1,0.2 mg/kg JYM595 applied intraperitoneally was shown to inhibit Carrageenan-induced paw edema in rats in a dose-dependent manner.Conclusion JYM595 exhibits in vitro and in vivo anti-inflammatory activity,which possesses therapeutic potential for the treatment of inflammatory diseases.

关 键 词：多肽 Α-MSH 炎症 抗炎活性 

分 类 号：R965[医药卫生—药理学]