【摘要】 目的 觀察長期大量酒精攝入對大鼠心肌結構及心肌組織中丙二醛(MDA)、超氧化物歧化酶(SOD)和金屬硫蛋白(MT)含量的影響,探討氧化應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,隨機分為2組,即對照組20只和模型組25只。模型組酒精濃度從5%、10%、20%和30%依次各自由飲1周,然后遞增至36%后以該濃度維持飼喂。對照組每日飲用與模型組酒精同等熱量的葡萄糖水。6個月后,觀察大鼠心肌組織的形態學改變及超微結構的變化,測定心肌組織中MDA、SOD及MT的含量。結果 模型組大鼠心肌細胞排列紊亂、間質充血、炎細胞浸潤、線粒體腫脹、空泡形成、肌絲溶解、核膜不規則和核仁裂解。心肌組織中MDA含量明顯升高(Plt;0.01),SOD活力含量明顯降低(Plt;0.01),MT含量明顯降低(Plt;0.01)。 結論 長期攝入大量酒精可使氧自由基代謝失衡,導致心肌損傷。氧化應激在酒精性心肌病發病機制中發揮著重要的作用。【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.
Retinopathy of Prematurity (ROP) is a blinding eye disease characterized by abnormal retinal vascular proliferation and is a major cause of visual impairment in children. Its pathogenesis is complex, involving multiple factors such as hyperoxia exposure, hypoxic compensation, oxidative stress, inflammatory responses, and abnormal angiogenesis, with oxidative stress playing a central role. It is characterized by excessive production of reactive oxygen species and impaired antioxidant function, leading to retinal vascular endothelial cell damage, formation of avascular areas, and abnormal vascular proliferation. Studies have shown that oxidative stress can promote the development and progression of ROP through vascular damage, nitrooxidative stress synergy, and interference with cellular metabolism. Current treatment strategies mainly include antioxidant agents (such as vitamin C, vitamin E, and lutein), signal pathway regulatory agents (such as nuclear factor erythroid 2-related factor 2 activators, signal transducer and activator of transcription 3 inhibitors), corticosteroids (such as Triamcinolone and Dexamethasone), and adrenergic receptor antagonists (such as Propranolol), but their efficacy and safety still require further validation. In the future, multidisciplinary collaboration should be strengthened to further explore the interactions between oxidative stress and other pathological mechanisms, and long-term follow-up studies should be conducted to develop safer and more effective strategies for the prevention and treatment of ROP, thereby improving the visual outcomes of preterm infants.
