南方医科大学学报

南方医科大学学报 ›› 2018, Vol. 38 ›› Issue (10): 1255-.doi: 10.12122/j.issn.1673-4254.2018.10.17

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低剂量乙醇对糖尿病大鼠心肌损伤后NF-κB表达的影响

宣玲，陈斌，郭建路，康品方，陶敏，高琴，唐碧，张恒   

  • 出版日期:2018-10-20 发布日期:2018-10-20

Effect of low-dose ethanol consumption on expression of nuclear factor-κB in diabetic rats with myocardial injury

  • Online:2018-10-20 Published:2018-10-20

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摘要： 目的探讨低剂量乙醇对糖尿病大鼠心肌损伤后核因子-κB（NF-κB）表达的影响。方法实验大鼠分为3组：正常对照组， 糖尿病组和糖尿病+低剂量乙醇组。后两组大鼠腹腔注射链脲佐菌素55 mg/kg复制糖尿病大鼠模型，糖尿病+低剂量乙醇组于 造模成功1周后给予2.5%（20 mg/kg/d）乙醇日常饮用，1周后改为5%（39.45 mg/kg/d）的乙醇持续至8周。小动物超声测定心室 心功能变化，透射电镜观察心肌超微结构变化，测定血浆白介素-1（IL-1），白介素-4（IL-4）的变化，蛋白印迹检测左室心肌组织 NF-κB、IKK的蛋白表达，免疫组化测定心肌组织NF-κB的蛋白的胞内定位分布，测定心肌组织4-HNE的变化。结果与对照组 比较，糖尿病组左室收缩及舒张功能降低，血浆IL-1水平、心肌组织4-HNE表达增加（P<0.01），血浆IL-4水平降低（P<0.01），心 肌组织NF-κB、IKK的蛋白表达增加（P<0.01），NF-κB蛋白在胞内分布增加，透视电镜显示心肌肌丝断裂、肌原纤维结构不完整、 线粒体损伤。与糖尿病组相比，低剂量乙醇干预组大鼠左室收缩和舒张功能得到了改善，心肌肌原纤维和线粒体损伤减轻，降 低了血浆IL-1及心肌组织4-HNE水平（P<0.01）及NF-κB、IKK的蛋白表达（P<0.01），NF-κB蛋白胞内分布减少，血浆IL-4水平 升高（P<0.01）。结论糖尿病大鼠心肌损伤时，心肌组织NF-κB表达增加，低剂量乙醇干预使NF-κB的表达降低，提示NF-κB信 号通路参与低剂量乙醇对糖尿病损伤心肌的保护作用。

Abstract: Objective To investigate the effect of low-dose ethanol on the expression of nuclear factor-κB (NF-κB) in diabetic rats with myocardial injury. Methods Rat models of diabetes were established by an intraperitoneal injection of 55 mg/kg streptozotocin (STZ). After successful modeling, the rats were given 2.5% ethanol (daily dose of 20 mg/kg) for 1 week, followed by 5% ethanol (daily dose of 39.45 mg/kg) for another 7 weeks. Normal rats without STZ injection and diabetic rats without ethanol treatment serve as the normal control and diabetic model groups, respectively. The ventricular function of the rats was determined using echocardiography. The plasma levels of interleukin-1 (IL-1) and IL-4 were detected in the rats, and the expressions of 4-HNE, NF-κB and IKK proteins in the left anterior myocardium was evaluated using immunohistochemistry or Western blotting; the ultrastructural changes of the myocardium were observed using transmission electron microscopy. Results Compared with the normal control group, the diabetic rats showed significantly lowered systolic and diastolic functions of the left ventricle, increased plasma level of IL-1 and myocardial 4-HNE expression (P<0.01), decreased plasma level of plasma IL-4 (P<0.01), and increased myocardial expressions of NF-κB and IKK proteins (P<0.01). Transmission electron microscopy revealed myofibrillar rupture, incomplete myofibrillar structure and mitochondrial damage in the cardiac myocytes in the diabetic rats. Compared with the diabetic rats, the rats with low-dose ethanol treatment exhibited improved systolic and diastolic functions of the left ventricle, milder myocardial myofibrillar and mitochondrial damages, and significantly lowered plasma IL-1 level and myocardial expressions of 4-HNE, NF-κB and IKK (P<0.01), and increased plasma IL-4 level (P<0.01). Conclusions NF-κB expression is increased in the myocardium of diabetic rats with myocardial injury, and low-dose ethanol consumption lowers myocardial expression of NF-κB in diabetic rats, suggesting the involvement of NF-κB signaling pathway in the protective effect of low-dose ethanol against myocardial injury in diabetes mellitus.