Study on the Mechanism of Chlorogenic Acid Regulating NLRP3 Inflammasome to Improve Atherosclerosis
Objective:To investigate the effects of chlorogenic acid on the NLRP3 inflammasome in a mouse model of atherosclerosis(AS).Methods:Eight male C57BL/6J mice were fed a regular diet as the control group(Control).Forty ApoE-/-mice were randomly divided into the model group(Model),low-dose chlorogenic acid group(CGA-L),medium-dose chlorogenic acid group(CGA-M),high-dose chlorogenic acid group(CGA-H),and simvastatin group(SIMV).All groups except for the control were fed a high-fat diet for 12 weeks to induce atherosclerosis confirmed by Oil Red O staining.After model confirmation,mice in CGA-L,CGA-M,and CGA-H groups were orally gavaged with chlorogenic acid at doses of 5,10,and 20 mg/kg/day respectively;Control and Model groups received 10 mL/kg/day of saline;SIMV group received simvastatin at 3 mg/kg/day,for 6 weeks.Serum levels of TC,TG,HDL-C,LDL-C were measured using an automatic biochemical analyzer;expression of IL-1β and IL-18 was assessed by ELISA;NLRP3 and Caspase-1 mRNA levels were evaluated by RT-qPCR.Results:Oil Red O staining showed extensive lipid deposition in the aortic intima of Model group mice,indicating successful modeling.Compared to the Control group,the Model group exhibited significantly elevated levels of TC,TG,LDL-C,IL-1β,IL-18,NLRP3,and Caspase-1 mRNA expression(P<0.01)and decreased HDL-C levels(P<0.01).Compared to the Model group,CGA-L,CGA-M,CGA-H,and SIMV groups showed significant reductions in TC,TG,LDL-C,IL-1β,IL-18,NLRP3,and Caspase-1 mRNA expression(P<0.05,P<0.01)and increased HDL-C levels(P<0.05,P<0.01).Among these,the CGA-H group demonstrated superior lipid-lowering and anti-inflammatory effects compared to CGA-L and CGA-M groups.Conclusion:Chlorogenic acid improves atherosclerosis by inhibiting the NLRP3 signaling pathway,reducing overexpression of inflammatory factors IL-1β,IL-18.
万方数据
维普
