【摘要】 目的:观察活化的黄嘌呤氧化酶抑制剂别嘌呤醇对慢性充血性心力衰竭大鼠心肌收缩力及细胞内钙含量的影响。方法:实验于2005-07/2006-02在南方医科大学南方医院心血管内科实验室进行。取34只雄性Wistar大鼠,单纯随机分成3组:①对照组(n=10):只做开胸手术,不结扎动脉。②模型组(n=12):结扎左冠状动脉的前降支,制备大面积心肌梗死后心力衰竭动物模型。③别嘌呤醇组(n=12):结扎冠状动脉后灌胃给予别嘌呤醇20mg/(kg·d)。梗死4周后麻醉状态下迅速剪下心脏,取心肌记录不同细胞外钙浓度[Ca2+]情况下细胞内钙[Ca2+]i含量和心肌收缩力的变化。用westernblot观察肌钙蛋白I降解的情况。结果:23只大鼠进入结果分析。①收缩期模型组心肌收缩力低于对照组和别嘌呤醇组[(21.7±2.1),(46.9±4.9),(42.9±4.2)mN/mm2,P<0.05],后2组间差异不显著(P>0.05)。②收缩期模型组细胞内钙低于对照组和别嘌呤醇组[(0.31±0.02),(0.44±0.04),(0.38±0.04)μmol/L,P<0.05],后2组间差异不显著(P>0.05)。③舒张末期模型组心肌收缩力和细胞内钙较正常对照组和别嘌呤醇组略有增加,但是差异不显著(P>0.05)。④别嘌呤醇可抑制肌钙蛋白I降解。结论:①黄嘌呤氧化酶抑制剂别嘌呤醇能改善心衰心肌钙分布的不平衡状态,使细胞内钙水平恢复接近正常水平,增加心肌的收缩力。②别嘌呤醇的强心作用在于它不但能够改善心衰心肌钙分布的不平衡状态,而且能够增加肌丝蛋白对钙的敏感性,改善异常的兴奋收缩耦联。更多还原

【Abstract】 AIM: To observe the effects of allopurinol, an activated xanthine oxidase (XO) inhibitor on myocardial contractility and intracellular calcium content of rats with chronic congestive heart failure. METHODS: The experiment was conducted in the laboratory of Department of Cardiology, Nanfang Hospital, Southern Medical University between July 2005 and February. Thirty-four male Wistar rats were selected and randomly divided into 3 groups: ①control group (n=10): The rats were given thoracotomy without artery ligation. ②model group (n=12): The anterior descending branch of left coronary artery was ligated to establish the animal models of heart failure after extensive myocardial infarction. ③allopurinol group (n=12): Allopurinol (20 mg/kg per day) was given to the rats after ligation of coronary artery. The rat hearts were cut quickly under anaesthesia after 4 weeks of infarction, and the myocardium was taken to record the [Ca2+]i content at various extracellular calcium and changes of myocardial contractility. Troponin I (Tn Ⅰ) degradation was detected by western blot analysis. RESULTS: A total of 23 rats were involved in the result analysis. ①The myocardial contractility at systolic phase of the model group was lower than the control group and allopurinol group [(21.7±2.1), (46.9 ±4.9), (42.9±4.2) mN/mm2, P < 0.05], and there was no significant difference between the latter two groups (P > 0.05). ②The [Ca2+]i at systolic phase of the model group was lower than the control group and allopurinol group [(0.31±0.02), (0.44±0.04), (0.38±0.04) μmol/L, P < 0.05], and there was no significant difference between the latter two groups (P > 0.05). ③The myocardial contractility and [Ca2+]i at late diastolic phase of the model group was slightly increased compared with the control group and allopurinol group, but had no significant differences (P > 0.05). ④Allopurinol could inhibit TnⅠ degradation. CONCLUSION: ①Allopurinol, a XO inhibitor can improve the unbalanced distribution of calcium in heart failure to make the [Ca2+]i recover to the normal level and enhance the myocardial contractility. ②Allopurinol can enhance cardiac function by improving unbalanced distribution of calcium, increase the sensitivity of myofilaments to calcium and improving abnormal excitation contraction coupling.更多还原