Bertuglia Silvia, Reiter Russel J
CNR Institute of Clinical Physiology, Faculty of Medicine, University of Pisa, Pisa, Italy.
J Pineal Res. 2007 Jan;42(1):55-63. doi: 10.1111/j.1600-079X.2006.00383.x.
Earlier studies showed that melatonin has powerful antioxidative effects on ischemia-reperfusion (I/R) injury in healthy hamsters. In the present study, the possible protective effects of melatonin in 10-month-old cardiomyopathic (CM) hamsters were evaluated in a model of I/R in the cheek pouches observed by intravital microscopy. In CM (BIO 14.6) hamsters diameter, red blood cell (RBC) velocity and flow in arterioles as well as lipid peroxide and nitrite/nitrate concentrations in the systemic blood, perfused capillary length, vascular permeability, and leukocyte adhesion were measured after melatonin injection (6 mg/kg intraperitoneally daily for 3 weeks), and after I/R. The influence of melatonin on the incidence of postischemic-reperfusion-induced ventricular tachycardia (VT) and ventricular fibrillation (VF) were also measured. Changes in the arteriolar response to NG-monomethyl-L-arginine (L-NMMA), a nitric oxide inhibitor, norepinephrine (NE), and angiotensin II (ANG II) were studied before and after melatonin injection (10 mg/kg intravenously). In CM hamsters, melatonin restored normal arteriolar responses to L-NMMA, NE, and ANG II. I/R elevated lipid peroxide and nitrate/nitrite levels, and vascular permeability while arteriolar diameter, RBC velocity, flow and capillary perfusion were reduced. These effects were more marked in CM versus healthy hamsters. During I/R melatonin reduced oxidative and nitrosative stress, vasoconstriction, leukocyte adhesion, and vascular permeability and increased capillary perfusion. Melatonin reduced the incidence of VT while VF during reperfusion disappeared totally. In conclusion, melatonin prevents both microvascular injury and ventricular arrhythmias during postischemic reperfusion by modulating the lipid peroxide overproduction and nitrative stress which are involved in the development of cardiomyopathy.
早期研究表明，褪黑素对健康仓鼠的缺血再灌注（I/R）损伤具有强大的抗氧化作用。在本研究中，通过活体显微镜观察颊囊I/R模型，评估了褪黑素对10月龄心肌病（CM）仓鼠的潜在保护作用。在CM（BIO 14.6）仓鼠中，在注射褪黑素（每天腹腔注射6 mg/kg，共3周）后以及I/R后，测量了小动脉直径、红细胞（RBC）速度和血流，以及全身血液中的脂质过氧化物和亚硝酸盐/硝酸盐浓度、灌注毛细血管长度、血管通透性和白细胞粘附。还测量了褪黑素对缺血再灌注诱导的室性心动过速（VT）和室颤（VF）发生率的影响。在静脉注射褪黑素（10 mg/kg）前后，研究了小动脉对一氧化氮抑制剂NG-单甲基-L-精氨酸（L-NMMA）、去甲肾上腺素（NE）和血管紧张素II（ANG II）反应的变化。在CM仓鼠中，褪黑素恢复了小动脉对L-NMMA、NE和ANG II的正常反应。I/R使脂质过氧化物和硝酸盐/亚硝酸盐水平以及血管通透性升高，而小动脉直径、RBC速度、血流和毛细血管灌注降低。与健康仓鼠相比，这些影响在CM仓鼠中更为明显。在I/R期间，褪黑素降低了氧化和亚硝化应激、血管收缩、白细胞粘附和血管通透性，并增加了毛细血管灌注。褪黑素降低了VT的发生率，而复灌注期间的VF完全消失。总之，褪黑素通过调节参与心肌病发展的脂质过氧化物过度产生和硝化应激，预防缺血再灌注后的微血管损伤和室性心律失常。
