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Protective Effects of Fluvoxamine against Ischemia/Reperfusion Injury in Isolated, Perfused Guinea-Pig Hearts

机译:氟伏沙明对离体灌注的豚鼠心脏缺血/再灌注损伤的保护作用

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摘要

Serotonin (5-hydroxytryptamine; 5-HT) is known to be activated during ischemia-reperfusion and triggers contractile dysfunction and pathological apoptosis. Here, the beneficial effects of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine was demonstrated on ischemia-reperfusion injury in guinea-pig hearts perfused using the Langendorff technique. The recovery (%) of left ventricular developed pressure (LVDP) by fluvoxamine (5×10~(-8) M) was 95.4% (control: 32%), which was consistent with the inhibition of mitochondrial Ca2+([Ca~(2+)]m) uptake induced by changes in the Ca2+ content and acidification of the perfusate, and similar to reperfusion following global ischemia in Langendorff-perfused hearts. Fluvoxamine inhibited the increase in [Ca~(2+)]m induced by changes in the Ca2+ content of the perfusate in perfused preparations of mitochondria, which was similar to the results obtained with the mitochondrial permeability transition pore (MPTP) opener atractyroside. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL)-positive cells were significantly less in fluvoxamine-treated hearts than in control hearts, with decreases in caspase-3 activity. These results suggest that SSRI inhibits opening of the MPTP by preventing [Ca~(2+)]m overload-induced apoptosis related to the endogenous accumulation of 5-HT in ischemia-reperfusion hearts.
机译:已知5-羟色胺(5-羟色胺; 5-HT)会在缺血再灌注过程中被激活,并引发收缩功能障碍和病理性细胞凋亡。在这里,使用Langendorff技术证明了选择性5-羟色胺再摄取抑制剂(SSRI)氟伏沙明对豚鼠心脏缺血再灌注损伤的有益作用。氟伏沙明(5×10〜(-8)M)对左心室发育压(LVDP)的恢复率为95.4%(对照:32%),与线粒体Ca2 +([Ca〜( 2 +)] m)是由灌流液中Ca2 +含量的变化和酸化引起的摄取,类似于在Langendorff灌注心脏中的整体缺血后的再灌注。氟伏沙明抑制了线粒体灌注制剂中灌注液中Ca2 +含量变化引起的[Ca〜(2 +)] m的增加,这与线粒体通透性转换孔(MPTP)开松剂白术苷的结果相似。在用氟伏沙明治疗的心脏中,末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记(TUNEL)阳性细胞明显少于对照心脏,同时胱天蛋白酶3活性降低。这些结果表明SSRI通过防止[Ca〜(2 +)] m超负荷诱导的缺血再灌注心脏内5-HT内源性积累相关的凋亡,从而抑制MPTP的开放。

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