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淀粉样β肽22 - 35对离体大鼠心脏产生负性变力作用。

Amyloid beta peptide 22-35 induces a negative inotropic effect on isolated rat hearts.

作者信息

Yousefirad Neda, Kaygısız Ziya, Aydın Yasemin

机构信息

Department of Physiology, Faculty of Medicine, University of Eskisehir Osmangazi Eskisehir, Turkey.

出版信息

Int J Physiol Pathophysiol Pharmacol. 2016 Dec 25;8(4):146-151. eCollection 2016.

PMID:28078053
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5209443/
Abstract

Evidences indicate that deposition of amyloid beta peptides (Aβs) plays an important role in the pathogenesis of Alzheimer disease. Aβs may influence cardiovascular system and ileum contractions. But the effect of amyloid beta peptide 22-35 (Aβ) on cardiovascular functions and contractions of ileum has not been studied. Therefore, the present study aimed to investigate the possible effects of this peptide on isolated rat heart and ileum smooth muscle. Langendorff-perfused rat heart preparations were established. The hearts were perfused under constant pressure (60 mmHg) with modified Krebs-Henseleit solution. Aβ at doses of 1, 10 and 100 nM significantly decreased left ventricular developed pressure (LVDP; an index of cardiac contractility) and maximal rate of pressure development of left ventricle (+dP/dt; another index of cardiac contractility). This peptide at doses studied had no significant effect on heart rate, coronary flow, monophasic action potential amplitude (MAPamp), MAP duration at 90% repolarization (MAP) and ileum contractions. We suggest that Aβ exerts a negative inotropism on isolated rat hearts with unchanged heart rate, coronary flow, MAPamp, MAP and smooth muscle contractility of ileum.

摘要

有证据表明,β淀粉样肽(Aβ)的沉积在阿尔茨海默病的发病机制中起重要作用。Aβ可能影响心血管系统和回肠收缩。但淀粉样β肽22 - 35(Aβ)对心血管功能和回肠收缩的影响尚未得到研究。因此,本研究旨在探讨该肽对离体大鼠心脏和回肠平滑肌的可能作用。建立了Langendorff灌注大鼠心脏标本。心脏在恒压(60 mmHg)下用改良的Krebs - Henseleit溶液灌注。1、10和100 nM剂量的Aβ显著降低左心室舒张末压(LVDP;心脏收缩力指标)和左心室压力上升最大速率(+dP/dt;另一个心脏收缩力指标)。在所研究的剂量下,该肽对心率、冠状动脉血流量、单相动作电位幅度(MAPamp)、90%复极化时的MAP持续时间(MAP)和回肠收缩没有显著影响。我们认为,Aβ对离体大鼠心脏具有负性肌力作用,而心率、冠状动脉血流量、MAPamp、MAP和回肠平滑肌收缩力不变。

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本文引用的文献

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Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer's disease.脑灌注不足和葡萄糖低代谢:关键病理生理调节因子促进神经退行性变、认知障碍和阿尔茨海默病。
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Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and apoptosis via a non-canonical p38alpha MAPK pathway.淀粉样轻链通过非经典的 p38alpha MAPK 通路诱导心肌细胞收缩功能障碍和细胞凋亡。
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PLoS One. 2009 Jun 24;4(6):e6033. doi: 10.1371/journal.pone.0006033.
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Alzheimer's beta-amyloid-induced depolarization of skeletal muscle fibers: implications for motor dysfunctions in dementia.阿尔茨海默病β-淀粉样蛋白诱导的骨骼肌纤维去极化:对痴呆症运动功能障碍的影响。
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