Yamashita N, Hoshida S, Otsu K, Taniguchi N, Kuzuya T, Hori M
The First Department of Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Br J Pharmacol. 2000 Oct;131(3):415-22. doi: 10.1038/sj.bjp.0703594.
We utilized a rat model of myocardial infarction to investigate whether manganese superoxide dismutase (Mn-SOD), an intrinsic radical scavenger, and tumour necrosis factor- alpha (TNF-alpha) and/or interleukin-1beta (IL-1beta) are involved in the late phase of ischaemic preconditioning (IP). IP was induced in anaesthetized rats by four 3-min left coronary artery (LCA) occlusions, each separated by 10 min of reperfusion. Twenty-four hours after the repetitive brief ischaemia, the LCA was occluded for 20 min followed by reperfusion for 48 h. IP reduced the infarct size by approximately 46% as determined after 48 h of reperfusion. Antisense oligodeoxynucleotides to Mn-SOD inhibited the increases in Mn-SOD content and activity, and abolished the expected decrease in myocardial infarct size. Sense or scrambled oligodeoxynucleotides did not abolish either Mn-SOD induction or tolerance to ischaemia/reperfusion. The simultaneous administration of the antibodies to TNF-alpha (0.5 ml) and IL-1beta (0.5 mg) prior to IP abolished the cardioprotection and the increase in Mn-SOD activity induced by IP. We conclude that the induction and activation of Mn-SOD, mediated by TNF-alpha and IL-1beta after IP, plays an important role in the acquisition of late-phase cardioprotection against ischaemia/reperfusion injury in rats.
我们利用大鼠心肌梗死模型来研究内源性自由基清除剂锰超氧化物歧化酶（Mn-SOD）以及肿瘤坏死因子-α（TNF-α）和/或白细胞介素-1β（IL-1β）是否参与缺血预处理（IP）的晚期阶段。通过对麻醉大鼠进行四次3分钟的左冠状动脉（LCA）闭塞来诱导IP，每次闭塞间隔10分钟的再灌注。在重复短暂缺血24小时后，将LCA闭塞20分钟，随后再灌注48小时。再灌注48小时后测定，IP使梗死面积减少了约46%。针对Mn-SOD的反义寡脱氧核苷酸抑制了Mn-SOD含量和活性的增加，并消除了预期的心肌梗死面积减小。正义或乱序寡脱氧核苷酸既没有消除Mn-SOD的诱导，也没有消除对缺血/再灌注的耐受性。在IP之前同时给予抗TNF-α抗体（0.5 ml）和抗IL-1β抗体（0.5 mg）消除了IP诱导的心脏保护作用以及Mn-SOD活性的增加。我们得出结论，IP后由TNF-α和IL-1β介导的Mn-SOD的诱导和激活在大鼠获得针对缺血/再灌注损伤的晚期心脏保护中起重要作用。
