Exploration of the effects of Huayu qutan formula on atherosclerosis in ApoE-/-mice based on EETs-mediated pyroptosis
OBJECTIVE To explore the effects and mechanism of Huayu qutan formula on atherosclerosis(AS)in ApoE-/-mice.METHODS Thirty ApoE-/-mice were randomly divided into model group,Huayu qutan formula group[20 g/(kg·d)],rosuvastatin group[1.55 mg/(kg·d)],with 10 mice in each group.Another 10 C57BL/6J mice were selected as normal control group.ApoE-/-mice were given high-lipid diet for 12 weeks to induce AS model.After modeling,each group was given relevant medicine or normal saline intragastrically,once a day,for 4 consecutive weeks.After the last administration,the levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),5,6-epoxyeicosatrienoic acid(5,6-EET),8,9-EET,11,12-EET,14,15-EET,interleukin-1β(IL-1β)and IL-18 in serum were detected;mRNA expressions of inhibitor of nuclear factor κB(IκB),nuclear factor κB(NF-κB),NOD-like receptor thermal protein domain associated protein 3(NLRP3),Caspase-1,IL-1β and IL-18 in the aortic tissue of mice were detected;protein expression levels of IκB,NF-κB,NLRP3,apoptosis-associated speck-like protein containing CARD(ASC),Caspase-1,gasdermin D(GSDMD),IL-1β and IL-18 in the aortic tissue of mice were detected.The morphological changes of the aortic tissue were observed.RESULTS Compared with model group,the serum levels of TC,TG,LDL-C,IL-1β and IL-18,the mRNA expressions of IκB,NF-κB,NLRP3,Caspase-1,IL-1β and IL-18 in aortic tissue,and the protein expressions of IκB,NF-κB,NLRP3,ASC,Caspase-1,GSDMD,IL-1β and IL-18 were all decreased significantly in Huayu qutan formula group and rosuvastatin group(P＜0.05),while the serum levels of 5,6-EET,8,9-EET,11,12-EET and 14,15-EET were increased significantly(P＜0.05).The aortic atherosclerotic plaques were alleviated significantly.CONCLUSIONS Huayu qutan formula can play role of anti-AS through EETs-mediated pyroptosis.
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