Kluge A, Zimmermann R, Münkel B, Verdouw P D, Schaper J, Schaper W
Max-Planck-Institute for Physiological and Clinical Research, Department of Experimental Cardiology, Bad Nauheim, Germany.
Cardiovasc Res. 1995 May;29(5):708-16.
Previous observations have shown that myocardium activates many adaptive processes after brief ischaemia. The aim of this study was to determine whether insulin-like growth factors (IGF) as well as their receptors and binding proteins (IGFBP), which control the activity of the IGF, may play an important role during these processes.
Ischaemia was induced in anaesthetised open chest pigs by two 10 min occlusions of the left anterior descending coronary artery, separated by 30 min of reperfusion, and followed by reperfusion up to 210 min. Tissue from the ischaemic area and from a non-ischaemic control region of the same heart was examined by means of northern blot, slot blot, and in situ hybridisation.
IGF-I, IGF-II, the type I receptor, the insulin receptor, and IGFBP-2-6 are constitutively expressed in porcine myocardium. In situ hybridisation showed that IGF-I and IGF-II are mainly transcribed by myocytes. Ischaemia/reperfusion led to an early and significant increase in IGF-II mRNA compared to non-sham controls but not in comparison with sham operated animals, which already showed a (not significantly) enhanced IGF-II expression. In each case the IGF-II mRNA levels are equal in the control and the experimental region of the same heart. Whereas IGF-II expression was already increased by experimental stress, IGFBP-5 mRNA was enhanced only by ischaemia/reperfusion. The expression of IGF-I, the receptors, and IGFBP-2, 3, 4, and 6 remained unchanged during the experimental protocol. IGFBP-1 was neither expressed nor induced in our model.
IGF-II acts like a stress-response gene activated by the experimental conditions (surgery, anaesthesia) and remains induced during following episodes of ischaemia/reperfusion. A possible interaction of IGFBP-5 with other components of the IGF system may contribute to the preconditioning response.
先前的观察表明，心肌在短暂缺血后会激活许多适应性过程。本研究的目的是确定胰岛素样生长因子（IGF）及其受体和结合蛋白（IGFBP）（它们控制IGF的活性）在这些过程中是否可能发挥重要作用。
通过两次10分钟的左前降支冠状动脉闭塞（中间间隔30分钟再灌注），对麻醉的开胸猪诱导缺血，随后再灌注长达210分钟。通过Northern印迹、狭缝印迹和原位杂交检查来自缺血区域和同一心脏非缺血对照区域的组织。
IGF-I、IGF-II、I型受体、胰岛素受体和IGFBP-2 - 6在猪心肌中组成性表达。原位杂交显示IGF-I和IGF-II主要由心肌细胞转录。与非假手术对照组相比，缺血/再灌注导致IGF-II mRNA早期显著增加，但与假手术动物相比无增加，假手术动物已显示出（不显著）增强的IGF-II表达。在每种情况下，同一心脏的对照区域和实验区域中IGF-II mRNA水平相等。虽然实验应激已使IGF-II表达增加，但IGFBP-5 mRNA仅在缺血/再灌注时增强。在实验过程中，IGF-I、受体以及IGFBP-2、3、4和6的表达保持不变。在我们的模型中未检测到IGFBP-1的表达或诱导。
IGF-II的作用类似于由实验条件（手术、麻醉）激活的应激反应基因，并在随后的缺血/再灌注发作期间持续诱导。IGFBP-5与IGF系统其他成分的可能相互作用可能有助于预处理反应。
