The Mechanism of Tianxiang Dan in Inhibiting Atherosclerosis Progression by Regulating the Autophagy-mTOR-AIM2 Inflammasome Axis Based on ApoE-/-and NLRP3-/-Mouse Models
GUO Longlong
SUN Longfei
ZHANG Li
ZHANG Xiaxia
GUO Lintao
WEI Wenijie
AN Dongqing
Abstract：Objective:To explore the effect of Tianxiang Dan in inhibiting the progression of atherosclerosis in mice by regulating the autophagy-mammalian target of rapamycin(mTOR)-absent in melanoma 2(AIM2)inflammatoryosome axis and its mechanism.Methods:Atherosclerosis models of ApoE knockout(ApoE-/-)mice were established by feeding with a high-fat diet for 12 weeks.The mice were divided into the model group(MD group),Tianxian Dan group[2.73 g/(kg·d),TXD group],ApoE-/-·NACHT,LRR and PYD domain protein 3(NLRP3)-/-+TXD group[2.73 g/(kg·d),NLRP3-/-group]and ApoE-/-·NLRP3-/-+RGFP966 group[400 μg/(kg·d),RGFP966 group],with 10 mice in each group.Ten C57BL/6J mice were fed with the basic diet as the blank control group(CO group).The plaque burden and stability were evaluated by oil red O staining,hematoxylin-eosin(HE)and Masson staining.The morphology of autophagosomes in aortic tissue was observed under transmission electron microscopy.The expressions of microtubule-associated protein 1 light chain 3(LC3),myosin-like BCL2-binding protein(Beclin-1),phosphorylated mTOR(p-mTOR),AIM2,Caspase-1,pyroptosis factor D(GSDMD),interleukin-1β(IL-1β),and interleukin-18(IL-18)proteins were detected by Western Blot.The mRNA expression of AIM2 was detected by immunohistochemistry and real-time fluorescence quantitative reverse transcription polymerase chain reaction(qRT-PCR).The levels of IL-1β and IL-18 in serum and aortic homogenate were determined by enzyme-linked immunosorbent assay(ELISA),and correlation analysis was performed.Results:Compared with the MD group,the protein expressions of AIM2,p-mTOR,Caspase-1,GSDMD,IL-1β,IL-18,and the serum levels of IL-1β and IL-18,the mRNA expression AIM2 in the TXD group decreased,while the protein expressions of LC3 and Beclin-1 increased(P<0.05).Compared with the TXD group,the protein expressions of AIM2,p-mTOR,Caspase-1,GSDMD,and AIM2 mRNA in the NLRP3-/-group increased,while the protein expressions of IL-18,LC3,Beclin-1,and the serum content of IL-18 decreased(P<0.05).Compared with the TXD group,the protein expression and serum content of IL-18 in the RGFP966 group decreased(P<0.05).Correlation analysis showed that the autophagy level was negatively correlated with AIM2,GSDMD,IL-1β,IL-18,and p-mTOR were LC3 correlated with AIM2,GSDMD,IL-1β,and IL-18.Conclusion:Tianxiang Dan could reduce plaque burden and enhance plaque stability and its mechanism might be related to the regulation of the autophagy-mTOR-AIM2 inflammatory pathway.
Keywords：atherosclerosisTianxian Danautophagy-mammalian target of rapamycin-absent in melanoma 2 inflammatory pathwaymiceexperimental study
Publication Date：2026-03-25
Online Publishing Date：2026-04-07(First online date of this platform, not the publication date of the document)
Pages：9( 860-868 )