中药新药与临床药理2025，Vol.36Issue(9)：1441-1449,9.DOI:10.19378/j.issn.1003-9783.2025.09.004
基于NLRP3/IL-1β通路探讨左归降糖舒心方调控巨噬细胞焦亡对糖尿病动脉粥样硬化小鼠的作用及机制
Mechanism of Zuogui Jiangtang Shuxin Formula in Regulating Macrophage Pyroptosis via the NLRP3/IL-1β Pathway in Diabetic Atherosclerotic Mice
摘要
Abstract
Objective To investigate the therapeutic effects and mechanism of Zuogui Jiangtang Shuxin Formula(ZJSF)on macrophage pyroptosis in diabetic atherosclerotic mice through the NOD-like receptor protein 3(NLRP3)/interleukin-1β(IL-1β)pathway.Methods Male Apoe-/-mice were acclimatized for 1 week,then injected intraperitoneally with low-dose streptozotocin(40 mg·kg-1)once daily for 5 consecutive days.After confirming fasting blood glucose(FBG)>11.1 mmol·L-1,mice were fed a high-fat diet for 12 weeks.After modeling,mice were randomly divided into model,Metformin(0.065 g·kg-1),and ZJSF(28.86 g·kg-1)groups(n=5 each),with C57BL/6 male mice as blank controls.Treatments were administered via gavage once daily for 8 weeks,while controls received distilled water.Serum triglycerides(TG),total cholesterol(TC)were detected by the automatic biochemical analyzer,FBG was tested by the glucometer,TNF-α,IL-18,and IL-1β levels were measured by ELISA.Aortic histopathology was assessed via HE and Masson staining;CD68 and Caspase-1 expression was detected by immunofluorescence;NLRP3/IL-1β pathway proteins were analyzed by Western Blot.Results Compared with blank controls,model mice showed significantly elevated FBG,TC,TG,TNF-α,IL-1β,and IL-18(P＜0.01);aortic intimal thickening,plaque protrusion,cholesterol crystals,foam cell accumulation,and thin fibrous caps were observed.CD68/Caspase-1 co-expression and NLRP3,IL-1β,GSDMD-N protein levels were upregulated(P＜0.01).Compared with the model group,ZJSF and Metformin groups exhibited reduced metabolic/inflammatory markers(P＜0.01),mitigated plaque formation,increased collagen content,and downregulated protein expression of CD68/Caspase-1 fluorescence intensity(P＜0.01)and NLRP3/IL-1β/GSDMD-N(P＜0.05,P＜0.01).Conclusion ZJSF improves glucolipid metabolism,attenuates inflammation,and stabilizes atherosclerotic plaques,potentially by suppressing macrophage pyroptosis via NLRP3/IL-1β pathway modulation.关键词
左归降糖舒心方/糖尿病动脉粥样硬化/糖脂代谢/炎症反应/巨噬细胞焦亡/NLRP3/IL-1β信号通路/小鼠Key words
Zuogui Jiangtang Shuxin Formula/diabetic atherosclerosis/glucolipid metabolism/inflammatory response/macrophage pyroptosis/NLRP3/IL-1β signaling pathway/mice分类
医药卫生引用本文复制引用
杨金伟,周毅,肖凡,喻嵘..基于NLRP3/IL-1β通路探讨左归降糖舒心方调控巨噬细胞焦亡对糖尿病动脉粥样硬化小鼠的作用及机制[J].中药新药与临床药理,2025,36(9):1441-1449,9.基金项目
国家自然科学基金项目(82205077) （82205077）
湖南省自然科学基金项目(2022JJ40315) （2022JJ40315）
湖南省教育厅资助科研项目(21B0390) （21B0390）
湖南省卫生健康委科研计划项目(D202303067601) （D202303067601）
中药粉体与创新药物省部共建国家重点实验室培育基地开放基金项目(21PTKF1016). （21PTKF1016）
