小钻木脂素类化合物戈米辛R的体外抗炎机制研究  

Research on in Vitro Anti-Inflammatory Mechanism of Gomisin R,the Lignans of Kadsura longipedunculata Finet et Gagnep

作　　者：覃朗[1] 莫单丹[2] 程娅[1] 李日伦[1] 龚小妹[2] 周小雷[2] 唐炳兰[2] QIN Lang;MO Dan-dan;CHENG Ya;LI Ri-lun;GONG Xiao-mei;ZHOU Xiao-lei;TANG Bing-lan(Department of Basic Medical Science,Guangxi Medical College,Nanning 530023,China;Guangxi Key Laboratory of Medicinal Resources Protection and Genetic Improvement,Guangxi Engineering Research Center of TCM Resource Intelligent Creation,Guangxi Botanical Garden of Medicinal Plant,Nanning 530023,China)

机构地区：[1]广西卫生职业技术学院医学基础部,南宁530023 [2]广西药用植物园,广西药用资源保护与遗传改良重点实验室,广西壮族自治区中药资源智慧创制工程研究中心,南宁530023

出　　处：《中国药学杂志》2022年第18期1543-1548,共6页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目资助(81660721);2017年广西科技重大专项资助(桂科AA18242040);2020年广西高校中青年教师科研基础能力提升项目资助(2020KY43007)。

摘　　要：目的通过脂多糖(LPS)诱导活化小鼠单核巨噬细胞系RAW264.7建立炎症模型,探讨小钻木脂素类化合物戈米辛R对炎症细胞增殖及炎症因子分泌的影响,评价其抗炎活性及机制。方法采用MTT比色法检测经LPS诱导的RAW264.7细胞存活率并计算半数抑制浓度(IC);采用ELISA法检测细胞上清液TNF-α、IL-1β、IL-6等炎症因子含量;利用RT-PCR法检测细胞TNF-α、IL-1β、IL-6、IκB-α、NF-κB p65的mRNA表达量;Western blot法检测细胞IκB-α及NF-κB p65蛋白表达量。结果与LPS模型组比较,戈米辛R可显著抑制LPS诱导的RAW264.7细胞增殖;降低细胞分泌TNF-α、IL-1β及IL-6的含量;升高LPS所致降低的IκB-αmRNA的表达量同时降低LPS引起升高的TNF-α、IL-1β、IL-6、NF-κB p65的mRNA表达量;升高IκB-α并降低NF-κB p65的蛋白表达量,显示出良好的剂量依赖性,具有统计学差异(P<0.05)。结论戈米辛R可通过抑制TNF-α、IL-1β、IL-6、NF-κB p65的mRNA和NF-κB p65蛋白的表达,增加IκB-αmRNA和IκB-α蛋白的表达,减少致炎因子TNF-α、IL-1β、IL-6的释放,从而发挥显著抗炎活性。OBJECTIVE To explore the effects of gomisin R(the lignans from Kadsura longipedunculata Finet et Gagnep.)on inflammatory cell proliferation and inflammatory factor secretion,and evaluate its anti-inflammatory activity and mechanism.METHODS Inflammation model was built by inducing and activating RAW264.7,the macrophage-monocyte lineage of rats,with lipopolysaccharide(LPS),then the cell survival rate of RAW264.7 was examined via MTT,and the half inhibition concentration(IC)was calculated.The levels of inflammatory factors,such as TNF-α,IL-1β,IL-6 in cell supernatant were tested via ELISA.The mRNA expression levels of cellular TNF-α,IL-1β,IL-6,IκB-αand NF-κB p65,were measured via RT-PCR.And the protein expression levels of cellular IκB-αand NF-κB p65,were measured via Western blot.RESULTS Compared with the LPS model set,gomisin R could notably inhibit the cell proliferation of RAW264.7 induced by LPS,decrease the TNF-α,IL-1βand IL-6 secretion of cells,enhance the mRNA expression levels of IκB-α,which were decreased by LPS,and in the meantime,lower the mRNA expressions of TNF-α,IL-1β,IL-6 and NF-κB p65,which was increased by LPS,and increase the protein expression of IκB-αwhile reduce that of NF-κB p65,the result of which was highly dependent on dose and the difference was statistically significant(P<0.05).CONCLUSION Gomisin R can inhibit the mRNA and NF-κB p65 protein expressions of TNF-α,IL-1β,IL-6 and NF-κB p65,and meanwhile increase the protein expressions of IκB-αmRNA and IκB-α,thus reducing the release of inflammatory factors such as TNF-α,IL-1βand IL-6,and bringing remarkable anti-inflammatory activity into full play.

关 键 词：戈米辛R 抗炎 RAW264.7 细胞因子 NF-ΚB 

分 类 号：R965[医药卫生—药理学]