【摘要】 目的 观察长期大量酒精摄入对大鼠心肌结构及心肌组织中丙二醛(MDA)、超氧化物歧化酶(SOD)和金属硫蛋白(MT)含量的影响,探讨氧化应激在酒精性心肌病大鼠中的作用。 方法 雄性健康SD大鼠45只,随机分为2组,即对照组20只和模型组25只。模型组酒精浓度从5%、10%、20%和30%依次各自由饮1周,然后递增至36%后以该浓度维持饲喂。对照组每日饮用与模型组酒精同等热量的葡萄糖水。6个月后,观察大鼠心肌组织的形态学改变及超微结构的变化,测定心肌组织中MDA、SOD及MT的含量。结果 模型组大鼠心肌细胞排列紊乱、间质充血、炎细胞浸润、线粒体肿胀、空泡形成、肌丝溶解、核膜不规则和核仁裂解。心肌组织中MDA含量明显升高(Plt;0.01),SOD活力含量明显降低(Plt;0.01),MT含量明显降低(Plt;0.01)。 结论 长期摄入大量酒精可使氧自由基代谢失衡,导致心肌损伤。氧化应激在酒精性心肌病发病机制中发挥着重要的作用。【Abstract】 Objective To observe the effect of longterm and large quantities of alcohol intake on myocardial structure of rats and the content of malondialdehyde (MDA), superoxide dismutase (SOD) and metallothionein (MT) in myocardium tissue. To study the effect of oxidative stress on the rats with alcoholic cardiomyopathy. Methods Fortyfive male and healthy SD rats were randomly divided into the control group (20 rats) and model group (25 rats).The alcoholic concentrate in model group was increased from 5%,10%,20% to 30% every week, and maintain free drinking mass concentration of 36% alcohol. The control group drink the same calories of glucose water. Six months later, the myocardial tissues were observed both in light microscope and electron microscope .The level of MDA、SOD and MT were tested in myocardium tissue. Results In the model rats, the cells of myocardial disarray, interstitial congestion, inflammatory cell infiltration, mitochondrial swelling, vacuole formation, melt filaments, irregular nuclear membrane and nucleolus cracking. The content of MDA incresed(Plt;0.01)and the activities of SOD decreased(Plt;001),levels of MT decreased (Plt;0.01) in the cardiac muscular tissues in the model group compared with the control group. Conclusion Longterm intake of large amounts of alcohol can break the balance of oxygen free radicals, which leading to the damage of myocardial. Oxidative stress plays an important role in the etiopathogenesis of alcoholic cardiomyopathy.
ObjectiveTo investigate the influence of Ataxia-telangiectasia mutated (ATM) activation on cellular oxidative stress induced by high glucose in bovine retinal capillary endothelial cells(BRECs). Methods The BRECs were treated by different culture medium with various glucose concentrations (5 mmol/L glucose, 30 mmol/L glucose, 30 mmol/L glucose+10 μmol/L KU55933) as normal glucose group, high glucose group and treatment group respectively.After the cells incubated for 48 hours, the protein expression of ATM, P-ATM, Mitogen-Activated Protein Kinase P38(P38), P-P38, Extracellular signal-regulated kinases(ERKs), P-ERKs was detected by Western blot; cellular ROS level was detected by Reactive Oxygen Species Assay Kit; propidium iodide/Hoechst staining was used for analysis of apoptosis; the expression of vascular endothelial growth factor (VEGF) in the supernatant was determined by Enzyme-Linked Immunosorbent Assay (ELISA); the paracellular permeability between endothelium cells was detected by FITC-dextran. ResultsCompared with the protein level of P-ATM, P-P38 and P-ERKs in high glucose group increased. Especially, P-P38, P-ERKs expressed much more than in high glucose group. The secretion of VEGF in high glucose group was higher than that in the normal glucose group but less than that in treatment group. The same tendency existed in ROS assay, apoptosis assay and paracellular permeability measuring. ConclusionsHigh glucose induced altered activation of ATM which might play a protective role in cellular oxidative stress. Deficiency of ATM might lead to ROS explosion, cell apoptosis and dysfunction of endothelial barrier. The mechanism might be associated with P38, ERKs and VEGF.