董彦彦,王甜甜,王琳,等.高强度间歇运动联合二甲双胍对1型糖尿病大鼠心脏病理性重塑的影响及机制研究[J].中华物理医学与康复杂志,2025,47(11):961-966
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| 高强度间歇运动联合二甲双胍对1型糖尿病大鼠心脏病理性重塑的影响及机制研究 |
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| DOI：10.3760/cma.j.cn421666-20250326-00269 |
| 中文关键词: 糖尿病 心肌病 高强度间歇运动 心脏重塑 二甲双胍 |
| 英文关键词: Diabetes mellitus Cardiomyopathy Interval training Cardiac remodeling Metformin |
| 基金项目:河南省科技攻关课题（242102321140） |
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| 中文摘要: |
| 目的 探讨高强度间歇运动联合二甲双胍对1型糖尿病（T1DM）大鼠心脏病理性重塑的影响及可能作用机制。 方法 采用随机数字表法将60只雄性SD大鼠分为对照组、模型组、运动组、药物组及联合组，每组12只大鼠。通过单剂量链脲佐菌素（60 mg/kg体重）腹腔注射方式将模型组、运动组、药物组及联合组大鼠制成T1DM模型。制模后对照组及模型组大鼠置于鼠笼内安静饲养，药物组大鼠给予二甲双胍灌胃（300 mg/kg体重，每天1次），运动组大鼠进行8周高强度间歇运动干预（3次/周），联合组大鼠给予二甲双胍灌胃及8周高强度间歇运动干预。经8周干预后测量各组大鼠体重、心脏指数（心脏重量/体重）及空腹血糖（FBG）水平，采用超声心动图评估大鼠心脏结构与功能；随后取各组大鼠心脏组织进行HE染色并测量心肌细胞宽度，采用Masson染色检测胶原容积分数，采用Western blot法测定心房钠尿肽（ANP）、脑钠尿肽（BNP）、转化生长因子-β（TGF-β）、胶原蛋白（Col）、过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）、磷酸化AMP激活蛋白激酶（p-AMPK）、兰尼碱受体（RyR）和肌浆网钙ATP酶（SERCA）蛋白表达量。 结果 与对照组比较，模型组心脏指数、FBG、左心室收缩末期内径（LVESD）、左心室舒张末期内径（LVEDD）均显著增加（P<0.05），体重、左心室缩短分数（LVFS）、左心室射血分数（LVEF）则明显下降（P<0.05），心肌细胞宽度和胶原容积分数明显增加（P<0.05），ANP、BNP、TGF-β、Col蛋白表达明显上调（P<0.05），PGC-1α、p-AMPK、RyR、SERCA蛋白表达明显下调（P<0.05）。与模型组比较，运动组、药物组及联合组上述指标均出现不同程度改善（P<0.05），并以联合组上述指标的改善幅度尤为显著（P<0.05）。 结论 高强度间歇运动联合二甲双胍可延缓T1DM大鼠心脏重塑，且疗效优于单一运动疗法或药物治疗，其作用机制可能与改善心肌纤维化和病理性心脏肥大、恢复线粒体功能及细胞内钙稳态、增强心功能有关。 |
| 英文摘要: |
| Objective To explore the effect on cardiac remodeling of combining high-intensity interval training with metformin in cases of type 1 diabetes mellitus (T1DM) and its possible mechanisms. Methods Sixty male Sprague-Dawley rats were randomly divided into control, model, exercise, drug and combination groups with twelve per group. T1DM was induced in all except the control group using a single intraperitoneal injection of streptozotocin (60mg/kg of body weight). The control and model groups were then housed without intervention, while the drug and exercise groups underwent metformin gavage (300mg/kg/day) or 8 weeks of high-intensity interval training (3 sessions/week), respectively. The combination group receiving both. After the training, body weight, a cardiac index (heart weight/body weight), and fasting blood glucose (FBG) were measured in all of the rats. Echocardiography assessed cardiac structure and function, and myocardial tissue was collected for HE or Masson staining to measure cardiomyocyte width and collagen volume fraction respectively. Protein expression and the levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), transforming growth factor-β (TGF-β), collagen (Col), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), phosphorylated AMP-activated protein kinase (p-AMPK), ryanodine receptor (RyR), and sarcoplasmic reticulum calcium ATPase (SERCA) were determined using western blotting. Results Compared with the control group, the model group showed significantly increased cardiac indices, FBG levels, and left ventricular end-systolic and end-diastolic diameters. But they had significantly decreased body weight, left ventricular fractional shortening and ejection fraction. Compared with the control group, there was a significant increase in the cardiomyocyte width and collagen volume fraction, as well as in ANP, BNP, TGF-β, and Col levels in the model group, along with downregulated PGC-1α, p-AMPK, RyR, and SERCA protein expression. Compared with the model group, the exercise, drug, and combination groups exhibited varying degrees of improvement in all these indicators, with the most pronounced effects in the combination group. Conclusions High-intensity interval training combined with metformin promotes cardiac remodeling in T1DM rats, outperforming either intervention alone. The mechanism may involve minimizing myocardial fibrosis and pathological hypertrophy, restoring mitochondrial function and intracellular calcium homeostasis. |
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