Mühlfeld Christian, Urru Michele, Rümelin Randi, Mirzaie Masoud, Schöndube Friedrich, Richter Joachim, Dörge Hilmar
Division of Electron Microscopy, Department of Anatomy, University of Göttingen, Göttingen, Germany.
Anat Rec A Discov Mol Cell Evol Biol. 2006 Mar;288(3):297-303. doi: 10.1002/ar.a.20315.
Neonatal rat hearts are more tolerant to ischemia compared to adult rat hearts. We hypothesized that opioid receptors and mitochondrial potassium channels are involved in the elevated ischemia tolerance of neonatal rats. Newborn rats were treated by an intraperitoneal injection with sodium chloride (placebo, Pla; n = 7), naloxone (Nal; n = 8), or K+ (ATP) channel blocker 5-hydroxydecanoate (HD; n = 8), or were left untreated (sham; n = 8). Thirty minutes after injection, the rats were sacrificed and hearts were arrested cardioplegically and fixed with aldehyde fixative 90 min after global ischemia at room temperature. For control, newborn rat hearts were fixed immediately after sacrifice. Ventricular tissue blocks were prepared for electron microscopy. Mitochondrial (volume-weighted mean volume of mitochondria) and cardiomyocyte volume (cellular edema index, CEI) were estimated to quantify the ischemic injury. Compared to control myocardium, CEI was increased by 244% +/- 39% in sham, 173% +/- 28% in Nal, 142% +/- 25% in HD, and 101% +/- 24% in Pla (P < 0.05 between groups). Volume-weighted mean volume of mitochondria was increased by 514% +/- 235% in sham, 341% +/- 110% in Nal, 458% +/- 149% in HD, and 175% +/- 70% in Pla. Differences between Pla and other groups were significant (P < 0.01 for all). No significant difference was observed between the other groups. Thus, ischemic injury was smallest with placebo, indicating a mechanism similar to preconditioning induced by the intraperitoneal injection. This response was attenuated by blockade of opioid receptors and mitochondrial potassium channels, suggesting their involvement in the elevated ischemia tolerance of newborn rat hearts.
与成年大鼠心脏相比，新生大鼠心脏对缺血的耐受性更强。我们推测阿片受体和线粒体钾通道与新生大鼠缺血耐受性的提高有关。新生大鼠通过腹腔注射氯化钠（安慰剂，Pla；n = 7）、纳洛酮（Nal；n = 8）或钾（ATP）通道阻滞剂5-羟基癸酸（HD；n = 8）进行处理，或不进行处理（假手术；n = 8）。注射30分钟后，处死大鼠，心脏用心脏停搏液停搏，并在室温下整体缺血90分钟后用醛类固定剂固定。作为对照，新生大鼠心脏在处死后立即固定。制备心室组织块用于电子显微镜检查。估计线粒体（线粒体的体积加权平均体积）和心肌细胞体积（细胞水肿指数，CEI）以量化缺血损伤。与对照心肌相比，假手术组的CEI增加了244%±39%，纳洛酮组增加了173%±28%，HD组增加了142%±25%，安慰剂组增加了101%±24%（组间P < 0.05）。线粒体的体积加权平均体积在假手术组增加了514%±235%，纳洛酮组增加了341%±110%，HD组增加了458%±149%，安慰剂组增加了175%±70%。安慰剂组与其他组之间的差异具有显著性（所有P < 0.01）。其他组之间未观察到显著差异。因此，安慰剂组的缺血损伤最小，表明存在一种类似于腹腔注射诱导的预处理的机制。阿片受体和线粒体钾通道的阻断减弱了这种反应，表明它们参与了新生大鼠心脏缺血耐受性的提高。
