芒果苷对糖尿病大鼠心肌细胞凋亡影响

Effect of mangiferin on myocardial apoptosis in diabetic rats

目的探讨芒果苷对肌醇依赖酶1介导的糖尿病大鼠心肌细胞凋亡影响。方法健康雄性SD大鼠50只,随机分为对照组,糖尿病组,芒果苷低、中、高剂量组(15、30、60 mg/kg),灌胃12周,糖尿病组与芒果苷组大鼠给予链脲佐菌素45 mg/kg建立糖尿病模型;测定大鼠血糖,心功能;用原位末端转移酶标记技术检测心肌细胞凋亡;免疫组织化学法检测肌醇依赖酶1(IRE1)、凋亡信号调节激酶1(ASK1)、c-Jun氨基末端激酶(JNK)表达。结果与对照组比较,糖尿病组大鼠血糖[(25.52±2.82)mmol/L]明显升高(P<0.01),左心室收缩压、左室内压最大上升和下降速率均明显降低,左室舒张末压明显升高(P<0.01),心肌细胞凋亡率[(25.63±1.41)%]增加(P<0.01),心肌细胞IRE1、ASK1、JNK蛋白表达明显增强(P<0.01);与糖尿病组比较,高剂量芒果苷组大鼠血糖[(12.04±1.86)mmol/L]降低,心肌细胞凋亡率[(13.22±1.71)%]下降(P<0.01),心功能明显改善,心肌细胞IRE1、ASKl、JNK蛋白表达均明显下调(P<0.01)。结论芒果苷可抑制糖尿病大鼠心肌细胞凋亡,其机制可能与下调血糖、内质网应激中IRE1介导的JNK信号通路表达有关。

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-Daw ley 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 d UTP-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 show ed 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.