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OA

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.