Catalpol decreases peroxynitrite formation and consequently exerts cardioprotective effects against ischemia/reperfusion insult
Catalpol decreases peroxynitrite formation and consequently exerts cardioprotective effects against ischemia/reperfusion insult
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梓醇可减少过氧亚硝酸盐的形成，从而对缺血/再灌注损伤发挥心脏保护作用
DOI：
10.3109/13880209.2012.740052
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发表时间：
2013-04-01
影响因子：
3.8
通讯作者：
Zhang, Haifeng
中科院分区：
文献类型：
--
作者：
Huang, Chaolian;Cui, Yongliang;Zhang, Haifeng
内容：过氧亚硝酸盐（ONOO-）的形成触发氧化/硝化应激，并有助于加剧心肌缺血/再灌注（MI/R）损伤。梓醇是一种环烯醚萜苷类化合物，广泛存在于紫露草的根中。包括在中国特有的唇形科（Phrymaceae）唇形科（Lamiales）中，发现其具有神经保护作用。然而，梓醇对MI/R损伤的作用尚未确定。目的：本研究调查梓醇是否减弱急性MI/R中的氧化/硝化应激。材料和方法：成年雄性大鼠经受30分钟的心肌缺血和3小时的再灌注，并且用盐水、梓醇（5 mg/kg，i. p.，结果：梓醇预处理可明显改善MI/R后心功能，减少MI/R后心肌梗死、心肌细胞凋亡和坏死（P均< 0.05）。同时，梓醇处理后ONOO-形成显著减少（3.01 +/- 0.22对4.66 +/- 0.53 pmol/mg载体蛋白，p < 0.05）。此外，梓醇增加Akt和内皮型一氧化氮合酶磷酸化，一氧化氮（NO）的产生，抗氧化能力和减少MI/R诱导的诱导型一氧化氮合酶的表达和超氧阴离子（中心点O-2（-））在I/R心脏的生产。PI 3 K抑制剂wortmannin不仅阻断梓醇诱导的Akt活化，而且减弱梓醇的所有有益作用。梓醇或ONOO-清除剂尿酸（5 mg/kg）抑制ONOO-形成可降低MI/R rates.Discussion和conclusion中的心肌梗死面积：总之，梓醇通过减弱ONOO-形成提供心肌保护，这可归因于增加的生理NO和减少的中心点O-2（-）产生。
Context: Peroxynitrite (ONOO-) formation triggers oxidative/nitrative stress and contributes to exacerbated myocardial ischemia/reperfusion (MI/R) injury. Catalpol, an iridoid glycoside, abundantly found in the roots of Rehmannia glutinosa L. that is included in the family Phrymaceae in the order Lamiales, endemic to China, was found to have neuroprotective effects. However, the effect of catalpol on MI/R injury has not been identified.Objective: This study investigated whether catalpol attenuates oxidative/nitrative stress in acute MI/R.Materials and methods: Adult male rats were subjected to 30 min of myocardial ischemia and 3 h of reperfusion and were treated with saline, catalpol (5 mg/kg, i.p., 5 min before reperfusion) or catalpol plus wortmannin (15 mu g/kg intraperitoneally injected 15 min before reperfusion).Results: Pretreatment with catalpol significantly improved cardiac functions, reduced myocardial infarction, apoptosis and necrosis of cardiomyocytes after MI/R (all p < 0.05). Meanwhile, ONOO- formation was markedly reduced after catalpol treatment (3.01 +/- 0.22 vs. 4.66 +/- 0.53 pmol/mg protein in vehicle, p < 0.05). In addition, catalpol increased Akt and endothelial nitric oxide synthase phosphorylation, nitric oxide (NO) production, anti-oxidant capacity and reduced MI/R-induced inducible nitric oxide synthase expression and superoxide anion (center dot O-2(-)) production in I/R hearts. PI3K inhibitor wortmannin not only blocked catalpol-induced Akt activation, but also attenuated all the beneficial effects of catalpol. Suppression of ONOO- formation by either catalpol or an ONOO- scavenger uric acid (5 mg/kg) reduced myocardial infarct size in MI/R rats.Discussion and conclusion: In conclusion, catalpol affords cardioprotection against MI/R insult by attenuating ONOO- formation, which is attributable to increased physiological NO and decreased center dot O-2(-) production.