Myocardial protection during heart surgery by IGF-1 and bcl-2 gene introduction.

胰岛素类似生长因子-1（IGF-1）已成为治疗晚期心脏失败的首选工具。另一方面，由于myocardial protection仍然是可行的，最近的研究建议，改变了Bcl-2家族蛋白的调节可能会在IGF-1的细胞保护行动中被纳入。这也很清楚，Bcl-2家族蛋白的内部定位是关键的，在对Mitochondria的死亡引发细胞色素c的调节释放中。因此，我们研究了IGF-1对Bcl-2家族蛋白表达的影响，并在孤立的大鼠心脏Mitochondria中释放细胞色素C。大鼠用IGF-1（3毫克/千克）注射治疗。Mitochondria在治疗后的12、24和36小时内离开了心脏。Western blot分析显示，Bcl-xL表达在大鼠心脏Mitochondria 24小时后IGF-1治疗，而Bax表达在相同的Mitochondria中最大限度地减少了调节 ... More ction.在IGF-1治疗后的任何时间，都检测到了细胞醇成分，无论是Bcl-xL非Bax蛋白。Bcl-2蛋白可在线粒体、细胞醇、微细胞组或核磷脂片段中分离。免疫性化学表现表明，IGF-1诱导的Bcl-xL在心脏中被确认为心脏细胞的过度表达。Isolated rat heart mitochon\a did not release cytochrome c without a respiratory substrate succinate even in the presence of 10-M CaイイD12+イエD1。However， respiring mitochondria released cytochrome c in a CaイイD12+イエD1 dependent manner。细胞色素C的发布是在Mitochondria发现的，是从IGF-1的心脏治疗中获得的。这些结果建议IGF-1不同的调节表达在大鼠心脏中Bcl-XL和Bax蛋白。IGF-1诱导抑制细胞色素C的释放可能表示一种机制，以抑制患者因端阶段心脏故障而死亡，或引起再灌注损害。Less（低）

Insulin like growth factor-1 (IGF-1) has become a promising tool for treatment with end-stage heart failure. Although the underlying mechanism for myocardial protection remains elusive, recent studies suggest that altered regulation of Bcl-2 family proteins may be involved in the cytoprotective action of IGF-1. It has also been clear that intracellular localization of Bcl-2 family proteins is crucial in regulating the release of death-promoting cytochrome c from mitochondria. Therefore, we have investigated the effect of IGF-1 on Bcl-2 family protein expression and cytochrome c release in isolated rat heart mitochondria. Rats were treated with intra-peritoneal injection with IGF-1(3mg/kg). Mitochondria were isolated from the heart 12, 24, and 36 hours after the treatment. Western blot analysis showed that Bcl-xL expression was maximally increased in the rat heart mitochondria 24 hours after IGF-1 treatment, while Bax expression was maximally down-regulated in the same mitochondrial fra … More ction. Neither Bcl-xL nor Bax protein was detected in the cytosol fraction at any time point after IGF-1treatment. Bcl-2 protein was undetectable in mitochondria, cytosol, microsome or nuclearmyofibrillar fraction. Immunohistochemical staining revealed that IGF-1-induced overexpression of Bcl-xL in the heart was confined to cardiomyocytes. Isolated rat heart mitochondria did not release cytochrome c without a respiratory substrate succinate even in the presence of 10μM CaィイD12+ィエD1. However, respiring mitochondria released cytochrome c in a CaィイD12+ィエD1 dependent manner. Cytochrome c release was attenuated in mitochondria obtained from the heart treated with IGF-1. These results suggest that IGF-1 differentially regulates expression of Bcl-xL and Bax proteins in the rat heart mitochondria. IGF-1-Induced inhibition of cytochrome c release from the mitochondria may represent a mechanism for inhibition of apoptotic cardimyocyte cell death in patients with end-stage heart failure, or with reperfusion injury. Less