基于JAK2/STAT3通路探讨丹红注射液对慢性心力衰竭大鼠心肌细胞凋亡的影响OA

Objective To explore the effects and mechanism of Danhong Injection in cardiomyocyte apoptosis in rats with chronic heart failure(CHF)based on JAK2/STAT3 pathway.Methods A rat model of CHF was established by abdominal aortic narrowing.The modeled rats were divided into the model group,Danhong Injection group and captopril group according to random number table method,the sham-operation group was set up.The rats in each group were given corresponding drug by gavage for 15 consecutive days.Cardiac ultrasound was used to detect the ventricular structure and cardiac function indexes(LVEDD,LVESD,LVEF,LVFS),serum NT-proBNP,TNF-α and IL-6 were detected by ELISA,HE and Masson staining were used to observe the pathological changes of myocardial tissue and the characteristics of myocardial fibers,apoptosis rate of cardiomyocytes was detected by TUNEL method,RT-qPCR was used to detect the expressions of JAK2,STAT3,Bcl-2,Bax,Caspase-3 and Caspase-9 mRNA in myocardial tissue,the protein expressions of p-JAK2,JAK2,p-STAT3,STAT3,Bcl-2,Bax,Caspase-3 and Caspase-9 was detected by Western blot.Results Compared with the sham-operation group,rats in the model group were depressed,slow in activity,and had dark,dry and easy-to-lose hair,and purple paw nails and tongue;cardiac ultrasound showed a significant increase in LVEDD and LVESD(P<0.01),and a significant decrease in LVEF and LVFS(P<0.01);the contents of serum NT-proBNP,TNF-α and IL-6 significantly increased(P<0.01);cardiomyocytes arrangement disturbed with cellular hypertrophy,necrosis,collagen fiber hyperplasia,inflammatory cell infiltration and increased myocardial fibrosis(P<0.01),the apoptosis rate of cardiomyocytes was increased(P<0.01),the expressions of JAK2,STAT3 mRNA and p-JAK2,p-STAT3 protein in myocardial tissue significantly increased,the expressions of Bax,Caspase-3,Caspase-9 mRNA and protein significantly increased,and the expressions of Bcl-2 mRNA and protein significantly decreased(P<0.01).Compared with the model group,rats in Danhong Injection group and captopril group showed improved mental status,diet and activity,shiny hair,and red paw nails and tongue;LVEDD and LVESD significantly reduced,and LVEF and LVFS increased(P<0.01);the contents of NT-proBNP,TNF-α and IL-6 significantly decreased(P<0.01);myocardial tissue structure was slightly abnormal,collagen fiber proliferation and myocardial fiber steatosis were reduced,myocardial fibrosis rate was significantly decreased(P<0.01),the apoptosis rate of cardiomyocytes significantly decreased(P<0.01);the expressions of JAK2,STAT3 mRNA and p-JAK2,p-STAT3 protein in myocardial tissue significantly decreased,the expressions of Bax,Caspase-3,Caspase-9 mRNA and protein significantly decreased,and the expressions of Bcl-2 mRNA and protein significantly increased(P<0.01).Conclusion Danhong Injection may reduce cardiomyocyte apoptosis by inhibiting JAK2/STAT3 pathway,improve myocardial tissue damage and promote the recovery of cardiac function in CHF rats.