Effects of Danggui Sini Granules(当归四逆颗粒)on Cardiomyocyte Apoptosis and Vasoactive Factors in Rat Models of Coronary Heart Disease with Cold Congealing and Blood Stasis Syndrome
Objective To explore the possible mechanism of Danggui Sini Granules(当归四逆颗粒)in treat-ment of coronary heart disease with cold congealing and blood stasis syndrome.Methods Fifty SD rats were randomly divided into a blank group,a model group,a Danshen Pill(丹参滴丸)group,and a low-and high-dosage Danggui Sini Granules group,with 10 rats in each group.Except for the blank group,the rat model of coronary heart disease with cold congealing and blood stasis syndrome was established by repeated cold stimulation at low temperature com-bined with intraperitoneal injection of posterior pituitary hormone in all other groups.In the 6th week of modelling,0.073 g·kg·d-1 of compound Danshen Pill was given to the Danshen Pill group,20.2 and 40.4 g·kg-1·d-1 of Danggui Sini Granules were given to the low-and high-dose Danggui Sini Granules groups,respectively,and 0.2 ml/10 g of sterile water was given to the blank group and the model group,all for 2 consecutive weeks.The general conditions of the rats were recorded,and the body mass was compared weekly.At the end of the intervention,electrocardiogram,blood rheological indexes,including whole blood low-cut viscosity,whole blood high-cut viscosity,erythrocyte aggre-gation index,and cardiac index were detected to evaluate the effect of the medication,and HE staining was used to observe the myocardial histopathological changes,TUNEL staining to detect the apoptotic situation of cardiomyo-cytes,and ELISA to detect the serum thyroid-stimulating hormone(TSH),free triiodothyronine(FT3),free tet-raiodothyronine(FT4)levels and thromboxane B2(TXB2),6-keto-prostaglandin F1α(6-Keto-PGF1α),endothelin 1(ET-1),and nitric oxide(NO)levels.Results Compared with the blank group at the same time point,the body mass of rats in the remaining groups decreased at all time points(P<0.05 or P<0.01);compared with the model group at the same time point,the body mass of rats in high-dose Danggui Sini Granules group and Danshen Pill group increased at the 6th and 7th weeks(P<0.05 or P<0.01).In the blank group,the S-T segment of the electrocardio-gram was close to the isoelectric line,the myocardial structure was regular,the fibres were closely arranged,and the nuclei of the cells were intact and neatly aligned;in the model group,the S-T segment of the electrocardiogram signifi-cantly elevated,and the arrangement of the myocardial fibres was obviously disordered,with myocardial cells appear-ing to be swollen,necrotic,and infiltrated by inflammatory cells,and the apoptosis-positive cells of the cardiac mus-cle cells obviously increased;in each of the medication groups,the electrocardiogram had a lowered S-T segment,and myocardial fibres were aligned,myocyte structure and morphology were improved,inflammatory cells reduced,and the number of apoptosis-positive cells significantly reduced.Compared with the blank group,the cardiac index,whole blood high cut viscosity,whole blood low cut viscosity,erythrocyte aggregation index increased in the model group,and the serum levels of TSH,FT3,FT4,NO,6-Keto-PGF1α significantly reduced,and the levels of ET-1 and TXB2 significantly increased(P<0.05 or P<0.01).Compared with the model group,the levels of cardiac index,whole blood high cut viscosity,whole blood low cut viscosity,erythrocyte aggregation index,ET-1 and TXB2 signifi-cantly decreased and the levels of NO and 6-Keto-PGF1αsignificantly increased in each medication group,and the se-rum levels of TSH,FT3,and FT4 elevated in the high-dose Danggui Sini Granules group and Danshen Pill group(P<0.05 or P<0.01).The serum TSH level of rats in the low-dose Danggui Sini Granules group was lower than that in Danshen Pill group and the high-dose Danggui Sini Granules group(P<0.01).Conclusion Danggui Sini Granules have the effect of alleviating myocardial injury in coronary heart disease with cold congealing and blood stasis syn-drome,and its mechanism may be related to reducing myocardial cell apoptosis,improving energy metabolism,and regulating the level of vasoactive factors.