芒果苷对糖尿病大鼠心肌细胞凋亡影响

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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 investigate the effect of mangiferin on cardiomyocyte apoptosis induced by inositol 1 in diabetic rats. Methods Fifty healthy male Sprague Dawley rats were randomly divided into control group, diabetic group and low, medium and high dose mangiferin groups (15, 30, and 60 mg / kg) for 12 weeks. The diabetic group and mangiferin group Rats were given streptozotocin 45 mg / kg to establish the model of diabetes mellitus; the blood glucose and cardiac function were measured; the apoptosis of cardiomyocytes was detected by in situ terminal transaminase labeling; the activity of inositol 1 (IRE1) , Apoptosis signal-regulated kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK). Results Compared with the control group, the blood glucose (25.52 ± 2.82 mmol / L) was significantly increased in the diabetic group (P <0.01), the left ventricular systolic pressure and the maximal increase and decrease rate of left ventricular pressure were significantly decreased, while the left ventricular diastolic (P <0.01). The apoptosis rate of cardiomyocytes was significantly increased (P <0.01), the apoptosis rate of cardiomyocytes was increased (25.63 ± 1.41)% (P <0.01) and the expression of IRE1, ASK1 and JNK was significantly increased (12.04 ± 1.86) mmol / L], the apoptosis rate of cardiomyocytes was decreased (13.22 ± 1.71%) (P <0.01), the cardiac function was significantly improved, the number of myocardial cells The protein expressions of IRE1, ASK1 and JNK were significantly down-regulated (P <0.01). Conclusion Mangiferin can inhibit myocardial cell apoptosis in diabetic rats. The mechanism may be related to down-regulation of IRE1-mediated JNK signaling pathway in glucose and endoplasmic reticulum stress.
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