中国药理学通报2024,Vol.40Issue(9):1766-1772,7.DOI:10.12360/CPB202312016
香青兰总黄酮调控TMAO介导的JAK/STAT轴抗大鼠动脉粥样硬化及RAW264.7细胞炎症的研究
Effect of total flavonoids of Dracocephalum moldavica on TMAO-mediated JAK/STAT axis against atherosclerosis in rats and inflammation in RAW264.7 cells
摘要
Abstract
Aim To investigate the protective effect of total flavonoids of Dracocephalum moldavica(TFDM)on atherosclerosis in rats and the inflammation of mouse macrophage RAW264.7 aggravated by trimeth-ylamine N-oxide(TMAO)and its possible mecha-nism.Methods The AS model of SD rats was estab-lished by high-fat diet feeding combined with intraper-itoneal injection of vitamin D3.The rats were divided into control group,model group,simvastatin group(15 mg·kg-1)and TFDM group(60,30,15 mg·kg-1).Biochemical method was used to detect the levels of se-rum total cholesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDL-C).HE staining was used to detect the pathological changes of aortic tissue.ELISA kit was used to detect the expression of TMAO,IL-1β,IL-6 in serum and TNF-α in liver tis-sue.Western blot was used to detect the expression of JAK,STAT and TNF-α protein in aorta.In addition,RAW264.7 macrophages were cultured in vitro,and LPS+TMAO was used to establish a macrophage in-flammation model,which was intervened by TFDM(100,50,25 mg·L-1).CCK-8 was used to determine cell viability and proliferation,and RT-qPCR was used to detect the expression of TNF-α,IL-6,JAK and STAT mRNA in cells.Results TFDM could significantly down-regulate the levels of serum TC,TG,LDL-C,ser-um TMAO,IL-1β,IL-6 and liver TNF-α,reduce aortic plaque deposition,and down-regulate the protein ex-pression of TNF-α,JAK and STAT in aorta.In addi-tion,TFDM intervention can significantly down-regulate the expression of TNF-α,IL-6,JAK,STAT mRNA and the expression of JAK,STAT protein.Conclusion TFDM can reduce the content of TMAO in serum,in-hibit JAK/STAT inflammatory signaling pathway and slow down the occurrence of inflammation,playing an anti-AS role.关键词
香青兰总黄酮/动脉粥样硬化/肠道菌群/氧化三甲胺/炎症反应/JAK/STAT信号通路Key words
total flavonoids of Dracocephalum mold-avica/atherosclerosis/intestinal flora/trimethylamine oxide/inflammatory reaction/JAK/STAT signaling pathway分类
医药卫生引用本文复制引用
曹文疆,杜春妍,黄川生,赵云丽,马晓莉,袁勇,王新春..香青兰总黄酮调控TMAO介导的JAK/STAT轴抗大鼠动脉粥样硬化及RAW264.7细胞炎症的研究[J].中国药理学通报,2024,40(9):1766-1772,7.基金项目
兵团科技计划项目重点领域科技攻关计划(No 2022AB020) (No 2022AB020)
国家自然科学基金资助项目(No 81960766) (No 81960766)