Decoction for warming Yang and removing toxin stabilizes atherosclerotic vulnerable plaque via regulating NLRP3/Caspase-1 pathway
Objective It is to explore the effects of decoction for warming Yang and removing toxin on blood lipids,plaque stability and expressions of receptor-interacting protein kinase 1 ( RIPK1 ),NLR-family Pyrin domain-containing protein 3 (NLRP3),and Caspase-1 in aortic tissues in atherosclerotic rats.Methods Forty healthy adult Wistar rats were fed with high-fat diet and intraperitoneally injected with vitamin D3 to establish models of atherosclerosis.35 successfully modeled rats were randomly divided into model group,simvastatin group,and the low,medium,and high dose groups of decoction for warming Yang and removing toxin,with 7 rats in each group.The rats were continued to fed with high-fat diet for 12 weeks,during which the low,medium,and high dose groups of decoction for warming Yang and removing toxin were given decoction for warming Yang and removing toxin 11.55 g/(kg·d),23.10 g/(kg·d),and 46.20 g/(kg·d) by gavage,respectively,while the simvastatin group was administered with 2 mg/mL simvastatin solution 2.10 mg/( kg·d) by gavage,and the model group was administered with distilled water 0.2mL/10g by gavage,all once daily.On the second day after the last gavage,the serum levels of triacylglycerol ( TG),total cholesterol ( TC),low-density lipoprotein choles-terol ( LDL-C),and high-density lipoprotein cholesterol ( HDL-C) were measured by automatic biochemistry,the patholog-ical morphology of aortic tissues was observed by HE staining,and the protein expressions of phosphorylated RIPK1 ( p-RIPK1),RIPK1,NLRP3,and Caspase-1 in aortic tissues were detected by Western blot.Results The differences in ser-um levels of TC,TG,LDL-C,HDL-C and relative protein expressions of p-RIPK1,RIPK1,NLRP3,Caspase-1 in aortic tissues of rats were not significant between the low dose group of decoction for warming Yang and removing toxin and model group (all P>0.05),and there was little difference in the aortic tissue structure,and the overall stability of the plaque was poor.The serum levels of TC,TG,LDL-C and relative protein expressions of p-RIPK1,RIPK1,NLRP3,Caspase-1 in aortic tissues of rats in the medium and high dose groups of decoction for warming Yang and removing toxin were signifi-cantly lower,while the serum levels of HDL-C were significantly higher than those in the model group (all P<0.05),and their overall stability of plaques was better (P<0.05).There were no significant differences in the serum levels of TC,TG,LDL-C,HDL-C and relative protein expressions of NLRP3,Caspase-1 in aortic tissues between the high-dose group of decoction for warming Yang and removing toxin and simvastatin group (all P>0.05);the relative protein expressions of p-RIPK1 and RIPK1 in the high dose group and simvastatin group were significantly lower than those in the medium-dose group (all P<0.05);the differences in the protein relative expressions of p-RIPK1 and RIPK1 were not statistically signif-icant between the high dose group and simvastatin group (all P>0.05) and the structure of aortic tissues of the two groups were more complete.Conclusion Decoction for warming Yang and removing toxin has effects of anti-inflammation,lipid-regulating,and plaque-stabilizing,and its mechanism may be related to down-regulating RIPK1 expression and inhibiting the NLRP3/Caspase-1 pathway.
atherosclerosisdecoction for warming Yang and removing toxinNLRP3Caspase-1