雷公藤甲素通过调控AMPK/mTOR通路抑制脂肪细胞和巨噬细胞炎症机制研究  

Triptolide Exhibits Anti-inflammatory Effects on Adipocytes and Macrophages by Inhibition of AMPK/mTOR Pathway

作　　者：李雪丽[1] 刘钊[1] LI Xueli;LIU Zhao(Experimental Research Center,China Academy of Chinese Medical Sciences,Beijing Key Laboratory of Research of Chinese Medicine on Prevention and Treatment for Major Diseases,Beijing 100700,China)

机构地区：[1]中国中医科学院医学实验中心,北京市中医药防治重大疾病基础研究重点实验室,北京100700

出　　处：《辽宁中医药大学学报》2022年第12期24-29,F0003,共7页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：中央公益研究机构基础研究经费项目(ZZ13-YQ-081);中国中医科学院自主选题项目(ZZ2018019)。

摘　　要：目的研究雷公藤甲素对3T3-L1脂肪细胞、RAW264.7巨噬细胞和两种细胞共培养炎症细胞模型的抑制作用及可能机制。方法该研究采用脂多糖、细胞条件培养基和巨噬-脂肪细胞共培养构建脂肪细胞、巨噬细胞和模拟脂肪组织的细胞炎症模型,应用这些炎症模型来研究雷公藤甲素(0.005、0.010、0.020、0.040μmol·L^(-1))对脂肪细胞和巨噬细胞以及脂肪组织分泌细胞因子的影响,并探求其对脂肪细胞内AMPK/mTOR信号通路上关键蛋白表达和激活的调控作用。结果雷公藤甲素通过有效抑制脂肪细胞AMPKα的表达和磷酸化水平,增强mTOR的磷酸化程度以及刺激4E-BP1的表达和磷酸化,从而减少炎症状态时的脂肪细胞分泌调节活化正常T细胞表达和分泌的趋化因子(RANTES)、单核细胞趋化蛋白-1(MCP-1)、角化细胞衍生趋化因子(KC)、嗜酸细胞活化趋化因子(EOTAXIN)。雷公藤甲素也能抑制炎症状态的巨噬细胞分泌粒细胞-巨噬细胞集落刺激因子(GM-CSF)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、RANTES、MCP-1、KC和EOTAXIN。结论雷公藤甲素能有效抑制巨噬细胞、脂肪细胞及两者之间的炎症反应,是非常有潜力的降低肥胖患者脂肪慢性炎症的抗炎药物。Objective To study the inhibitory effect of triptolide on 3T3-L1 adipocytes,RAW264.7macrophages and two co-cultured inflammatory cell models.Methods In this study,lipopolysaccharide(LPS),conditioned medium and co-culture of macrophages and adipocytes were used to establish cell inflammatory models of adipocytes,macrophages and adipose tissue,the effects of triptolide(0.005,0.010,0.020 and 0.040μmol·L^(-1))on the secretion of cytokines by adipocytes,macrophages and adipose tissue were studied using these inflammatory models.And to explore its regulatory role on the expression and activation of key proteins in AMPK/mTOR signaling pathway in adipocytes.Results Triptolide can effectively inhibit the expression and phosphorylation of AMPKαin adipocytes,enhance the phosphorylation of mTOR,and stimulate the expression and phosphorylation of 4EBP1,it can reduce the release of RANTES,MCP-1,KC and EOTAXIN by adipocytes in inflammatory state.Triptolide also inhibited the secretion of GM-CSF,IL-6,TNF-α,RANTES,MCP-1,KC and EOTAXIN in inflammatory macrophages.Conclusion Triptolide can effectively inhibit the inflammatory reaction of macrophages and adipocytes,and it is a potential anti-inflammatory drug to reduce the chronic inflammation of adipocytes in obese patients.

关 键 词：雷公藤甲素 脂肪细胞 巨噬细胞 趋化因子 

分 类 号：R285.5[医药卫生—中药学]