Objective To observe the therapeutic effect and mechanism of Xinmaikang Prescription for mice with atherosclerosis(AS).Methods A high-fat diet feeding method was used to construct an AS ApoE-/-mouse model.Successful modeled mice were randomly divided into four groups,i.e.,the model group,the Atorvastatin group,and the low-and high-dose groups of Xinmaikang Prescription,with eight mice in each group.A normal group(eight mice)was also set up.After 12 weeks of corresponding intervention in each group,the pathological changes of aorta were observed by oil red O staining,enzyme-linked immunosorbent assay(ELISA)was used to determine the contents of interleukin 1β(IL-1β)and interleukin 18(IL-18)in serum,and real-time quantitative polymerase chain reaction(qPCR)was used to detect the mRNA expression levels of pyroptosis-associated proteins nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)and cysteine protein hydrolase 1(Caspase-1)as well as inflammatory factors IL-1β and IL-18 in aorta tissues,and Western Blot method was used to detect the protein expression levels of NLRP3,Caspase-1,IL-1β and IL-18 in aortic tissues.Results Compared with the normal group,the intima thickness in the model group was significantly increased,and a large number of lipid plaques and inflammatory cell infiltration appeared in aorta,the contents of IL-1β and IL-18 in serum were elevated(P<0.01),and the mRNA and protein expression levels of NLRP3,Caspase-1,IL-1β and IL-18 in the aortic tissues were significantly increased(P<0.01);in the Xinmaikang Prescription high-dose group and Atorvastatin group,the lipid droplets and area of vulnerable plaques in aortic tissues were significantly reduced,and the serum levels of IL-1β and IL-18 were decreased(P<0.01),and the mRNA and protein expression of NLRP3,Caspase-1,IL-1β and IL-18 in aortic tissues were significantly reduced(P<0.01).Conclusion Xinmaikang Prescription may effectively reduce the inflammatory response and pyoptosis of vascular endothelial cells in AS model mice through regulating the NLRP3/Caspase-1/IL-1β signaling pathway,thus exerting the effect of preventing and treating AS.

Objective To explore the mechanism of Xinkang Prescription (Descurainiae Semen Lepidii Semen,Armeniacae Semen Amarum,Poria,Astragali Radix,Citri Reticulatae Pericarpium,Sparanii Rhizoma) for purging the lung and promoting diuresis in treating heart failure by regulating phosphorylation of phospholamban (PLN). Methods Forty-eight C57BL/6J mice were randomly divided into sham-operation group,model group,low-,medium-and high-dose Xinkang Prescription groups(0.455,0.91,1.82 g·kg-1),as well as Entresto group (25 mg·kg-1),with eight mice in each group. The model of ischemic heart failure was established by ligating the left anterior descending coronary artery in mice. After the model was successfully replicated,mice were orally administered with the above-mentioned dosages of Xinkang Prescription and Entresto once a day for four weeks,while sham-operation group and model group were given 0.9％ sodium chloride solution by gavage at the same time. Echocardiography was used to detect the cardiac function of the mice in each group,including left ventricular ejection fraction (LVEF),left ventricular fractional shortening (LVFS),left ventricular end-diastolic dimension (LVEDD) and left ventricular end systolic diameter (LVESD). Hematoxylin-eosin (HE) staining was used to observe the pathological changes in cardiac tissue of mice. qRT-PCR was used to detect the mRNA expression of BNP. Western Blot and Jess were used to detect the expression of PLN,p-Thr17-PLN,p-Ser16-PLN,sarcoplasmic reticulum calcium ATPase 2a (SERCA2a),protein kinase A (PKA),p-PKA,Ca2+/calmodulin-dependent kinaseⅡ(CaMKⅡ) and p-CaMKⅡ in cardiac tissue,and to calculate the ratio of SERCA2a/PLN. The SERCA2a activity was determined by the inorganic phosphorus method.Results Compared with the sham-operation group,the model group showed a significant decrease in LVEF and LVFS(P<0.01) and a significant increase in LVEDD and LVESD (P<0.01). HE staining showed the fibril of cardiac muscle broke and disarranged,accompanied by inflammatory cell infiltration. The mRNA expression of BNP was significantly up-regulated (P<0.01),and the protein expressions of p-Ser16-PLN,p-Thr17-PLN,p-PKA,the ratio of SERCA2a/PLN and SERCA2a activity were significantly down-regulated (P<0.01),while the expression of p-CaMKⅡ was up-regulated (P<0.01). Compared with the model group,LVEF and LVFS in medium-,high-dose Xinkang Prescription groups were significantly increased(P<0.01),while LVEDD and LVESD were significantly decreased (P<0.01). HE staining showed significant improvement in the pathological damage of cardiac tissue. The expression level of BNP was significantly decreased (P<0.01),while the protein expressions of p-Ser16-PLN,p-Thr17-PLN,p-PKA,the ratio of SERCA2a/PLN and SERCA2a activity were significantly increased (P<0.01). The protein expression of p-CaMKⅡ was remarkably decreased(P<0.05). Conclusion Xinkang Prescription can effectively improve cardiac function of mice with heart failure,which may be related to enhance phosphorylation levels of phospholamban.