苏木酮A通过抑制JAK2-STAT3信号通路发挥抗炎作用  

Sappanone A Plays An Anti-inflammatory Role by Inhibiting the JAK2-STAT3 Signaling Pathway

作　　者：邓成杰 马洪星 张华茜 胡月周 黄静 孙世芹 辛萍 DENG Chengjie;MA Hongxing;ZHANG Huaxi;HU Yuezhou;HUANG Jing;SUN Shiqin;XIN Ping(College of Pharmacy,Harbin Medical University-Daqing,Daqing 163319 Heilongjiang,China;Clinical Laboratory Department,Nanjing Lishui People's Hospital,Zhongda Hospital Lishui Branch,Southeast University,Nanjing 211200 Jiangsu,China;Department of Scientific Research and Teaching,Nanjing Lishui People's Hospital,Zhongda Hospital Lishui Branch,Southeast University,Nanjing 211200 Jiangsu,China)

机构地区：[1]哈尔滨医科大学大庆校区药学院,黑龙江大庆163319 [2]江苏省南京市溧水区人民医院检验科,江苏南京211200 [3]江苏省南京市溧水区人民医院科教科,江苏南京211200

出　　处：《中药新药与临床药理》2023年第12期1685-1690,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：黑龙江省省属高等学校基本科研业务费基础研究项目(JFQN202101);国家自然科学基金项目(81903763);黑龙江省自然科学基金项目(YQ2019H005);中国博士后科学基金(2019M661312);南京市溧水区人民医院引进人才科研启动基金(2021YJ01);大庆市指导性科技计划项目(zdy_2023-105)。

摘　　要：目的基于JAK2-STAT3信号通路探究苏木酮A(SA)在脂多糖(LPS)诱导的RAW264.7细胞模型中的抗炎作用和机制。方法MTT法检测苏木酮A、LPS、AG490对RAW264.7细胞活力的影响;建立LPS诱导的RAW264.7细胞炎性模型,通过ELISA法检测上清液中白细胞介素6(IL-6)的分泌水平;采用RT-PCR技术检测IL-6、酪氨酸激酶2(JAK2)和信号转导及转录激活因子3(STAT3)的mRNA表达;采用Western Blot法检测JAK2、磷酸化JAK2(p-JAK2)、STAT3及磷酸化STAT3(p-STAT3)的蛋白表达。结果与空白对照组比较,模型组的IL-6分泌水平明显增加,IL-6、JAK2和STAT3的m RNA表达上调,p-JAK2和p-STAT3蛋白表达水平升高(均P<0.01);与模型组比较,苏木酮A高剂量(5μg·mL-1)组明显降低了IL-6的含量,下调了IL-6、JAK2和STAT3的mRNA表达,抑制了p-JAK2和p-STAT3蛋白表达(均P<0.01)。结论苏木酮A可能通过抑制JAK2-STAT3信号通路以抑制促炎因子IL-6的分泌,从而发挥抗炎作用。Objective To investigate the anti-inflammatory effect and mechanism of sappanone A(SA)on lipopolysaccharide(LPS)-induced RAW264.7 cell model based on JAK2-STAT3 signaling pathway.Methods MTT assay was used to detect the effects of sappanone A,LPS and AG490 on RAW264.7 cell viability.The LPS-induced inflammatory model in RAW264.7 cells was established,and the secretion level of interleukin-6(IL-6)in the supernatant was detected by ELISA.mRNA expressions of IL-6,Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)were tested by RT-PCR.The protein expressions of JAK2,phosphorylated JAK2(p-JAK2),STAT3 and phosphorylated STAT3(p-STAT3)were determined by Western Blot.Results Compared with control group,IL-6 secretion level was significantly increased,mRNA expressions of IL-6,JAK2and STAT3 were up-regulated,and protein expressions of p-JAK2 and p-STAT3 were increased(all P<0.01)in model group.Compared with model group,high-dosed sappanone A(5μg·mL-1)was significantly decreased the secretion of IL-6,down-regulated the mRNA expressions of IL-6,JAK2 and STAT3,and inhibited the protein expressions of p-JAK2 and p-STAT3(all P<0.01).Conclusion Sappanone A may play an anti-inflammatory role by inhibiting the JAK2-STAT3 signaling pathway and hence inhibiting the secretion of IL-6.

关 键 词：苏木酮A RAW264.7细胞 抗炎 JAK2-STAT3 IL-6 

分 类 号：R285.5[医药卫生—中药学]