广州中医药大学学报2026,Vol.43Issue(8):2217-2225,9.DOI:10.13359/j.cnki.gzxbtcm.2026.08.027
瓜蒌通脉丸靶向PPARγ改善粥样动脉硬化小鼠血脂代谢与血管炎症
Gualou Tongmai Pills Ameliorates Lipid Metabolism and Vascular Inflammation in Atherosclerotic Mice via Targeting PPARγ
摘要
Abstract
Objective To observe the therapeutic effect and mechanism of Gualou Tongmai Pills(GLTMP)on atherosclerosis(AS)in mice.Methods Six normal C57BL/6J mice were used as a blank control group.Twenty-four ApoE-/-mice were randomly divided into four groups(n=6 per group):mode groupl,GLTMP group,rosiglitazone group,and GW9662(a PPARγ inhibitor)+GLTMP group.An atherosclerosis model was induced in ApoE-/-mice by feeding a highfat diet.After successful modeling,corresponding interventions were administered.Following treatment,plaque formation and pathological morphology were assessed by oil red O gross staining of the aorta,as well as oil red O,hematoxylin-eosin(HE)and Masson staining of the aortic root.Serum levels of triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were measured to evaluate lipid metabolism.Inflammatory cytokines interleukin-1β(IL-1β),interleukin 6(IL-6),and tumor necrosis factor α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).The protein expression levels of nuclear factor κB(NF-κB),peroxisome proliferatoractivated receptor γ(PPAR-γ),liver X receptor α(LXR-α),and ATP-binding cassette transporter A1(ABCA1)were measured by Western Blot and immunofluorescence staining.The interactions of PPARγ with LXRα and ABCA1 were verified by coimmunoprecipitation(Co-IP).Results Compared with the blank control group,the model group exhibited significant atherosclerotic plaques in the aorta,significantly increased serum levels of TG,TC,LDL-C,IL-1β,IL-6,and TNF-α,significantly decreased HDL-C level,significantly upregulated NF-κB protein expression,and significantly downregulated PPARγ,LXRα,and ABCA1 protein expression,the difference being statistically significant(P<0.05 or P<0.01).Compared with the model group,the GLTMP group showed reduced aortic plaques,decreased serum TG,TC,LDL-C and the above three inflammatory cytokine levels,increased HDL-C level,downregulated NF-κB protein expression,and upregulated PPARγ and LXRα expression,the difference being statistically significant(P<0.05 or P<0.01),with effects comparable to the positive control rosiglitazone.The effects of GLTMP were significantly blocked by the PPARγ inhibitor GW9662.Furthermore,protein-protein interactions were detected between PPARγ and LXRα,as well as between PPARγ and ABCA1.Conclusion GLTMP can improve lipid metabolism and inhibit vascular inflammation by targeting PPARγ and regulating the"PPARγ-LXRα-ABCA1"protein interaction as well as the"PPARγ/NF-κB/pro-inflammatory cytokine"axis,thereby delaying the progression of high-fat diet-induced atherosclerosis in ApoE-/-mice.关键词
瓜蒌通脉丸/动脉粥样硬化/血脂代谢/血管炎症/PPARγ/小鼠Key words
Gualou Tongmai Pills/atherosclerosis/lipid metabolism/vascular inflammation/PPARγ pathway/mice分类
医药卫生引用本文复制引用
吴嵩,陈玥,苑宇威,范新发,张鹏..瓜蒌通脉丸靶向PPARγ改善粥样动脉硬化小鼠血脂代谢与血管炎症[J].广州中医药大学学报,2026,43(8):2217-2225,9.基金项目
河北省重点研发计划项目(编号:21059010219D) (编号:21059010219D)