Abstract: Objective To explore the effect of mangiferin on myocardial apoptosis mediated by inlositol-requiring enzyme 1(IRE1)in diabetic rats.Methods Fifty healthy male Sprague-Dawley rats with the body weight of 250 to 280 g were selected and administered with 45 mg/kg streptozotocin intravenous injection to establish diabetes model;then the rats were randomly divided into 5 groups : normal group,diabetic group,and low-,moderate-,and high-dose mangiferin groups(with intragastric administration of 15,30,and 60 mg/kg·d for 12 weeks).The normal group and diabetic group were treated daily with normal saline intragastric administration.The blood glucose and cardiac function of the rats were determined;the myocardial apoptosis was assessed with terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling(TUNEL);and the expressions of IRE1,apoptosis signal-regulating kinase 1(ASK1),and c-Jun N-terminal kinase(JNK)were detected with immunohistochemistry.Results Compared with the normal group,the rats of diabetic group showed obviously increased blood sugar(P <0.01),significantly reduced left ventricular systolic pressure(LVSP)and positive and negative peak first derivative of pressure(±dp/dtmax),obviously increased left ventricular end-diastolic pressure(LVEDP)(P <0.01),and significantly increased rate of cardiomyocyte apoptosis(from 3.50±0.76% to 25.63±1.41%)(P <0.01).Compared with the rats of diabetic group,the rats with mangiferin treatment had a decreased myocardial apoptosis rate and improved protein expressions;for the rats with high dose mangiferin treatment,the myocardial apoptosis rate was decreased to 13.22±1.71(P <0.01)and the protein expressions of IRE1,ASKl and JNK were significantly reduced.Conclusion Mangiferin can inhibit myocardial apoptosis in diabetic rat and the effect may be related to the reductions of blood sugar and the inhibition JNK expression in endoplasmic reticulum stress.