Plasma soluble Fas, an inhibitor of apoptosis, definitely improves long-term prognosis of patients with chronic heart failure

本研究以陈旧性心肌梗死大鼠为模型，采用30只6周龄雄性大鼠，建立心肌梗死后心力衰竭模型，并以相同数量的大鼠进行假手术，观察血浆sFas（细胞凋亡抑制剂）对心力衰竭的影响，探讨sFas对心力衰竭的分子生物学生理学机制。作为对照。1999年我们成功地用左冠状动脉近端结扎法制备了急性心肌梗死后心力衰竭模型，2000年我们测定了心肌梗死后12周心力衰竭大鼠模型血浆sFas浓度。结果表明，心力衰竭时血浆sFas升高。此外，在大鼠心肌组织中，我们识别到TUNEL阳性的心肌细胞，这表明存在DNA断裂，作为凋亡的标志，Fas和Bax上调， ...更多信息 s诱导剂。心肌组织电镜观察可见心肌细胞肥大、变性，核变形。然而，没有观察到染色质的特异性浓缩、收缩、出芽和凋亡小体，这表明细胞凋亡。我们澄清了肌细胞纤维化的发现，这表明光学显微镜下的肌细胞死亡。此外，TUNEL阳性的心肌细胞的频率等于或小于1%。因此，电镜下没有凋亡的发现并不意味着心肌细胞中没有凋亡，而是电镜下的观察面积太小。随后，我们通过腹腔注射将sFas给予上述心力衰竭大鼠。然而，我们没有达到血浆sFas水平以产生显著的持续性升高，并且不能确认心力衰竭的改善。因为，血浆sFas的转换被认为是在腹腔内施用sFas中出乎意料地更早。因此，腹腔内施用sFas不被接受，因为sFas表达持续很长一段时间。结论：sFas基因治疗是实现心肌组织持续表达的必要条件。少

This study was aimed to clarify the molecular biophsiological mechanisms of heart failure, and to clarify whether plasma sFas, an inhibitor of apoptosis, can improve the long-term prognosis of rat with old myocardial infarction, as a model of heart failure.Experiments were performed on 30 6-wk-old male rat for suffering from heart failure caused by myocardial infarction, and the same number of rat for producing Sham operation, as a control. In 1999, we successfully performed to make a model of heart failure after acute myocardial infarction made by ligation of proximal site of left coronary artery.In 2000, we measured the plasma sFas concentration in 12 weeks heart failure rat model after the myocardial infarction. As a result, plasma sFas was clarified to elevate in heart failure. In addition, in the cardiac muscle tissue of the rat, we recognized TUNEL positive myocytes which suggested existence of DNA fragmentation, as a marker of apoptosis, and upregulation of Fas and Bax, apoptosi … More s inducers. In findings of electron microscope of cardiac muscle tissue, hypertrophy and degeneration of myocytes and deformity of myocytic nucleus were observed. However, specific condensation of chromatin, shrinkage, budding, and apoptotic body of myocytes, which suggested apoptosis, was not observed.We clarifled the findings of fibrosis in myocytes, which suggested myocyte cell death by optical microscope. In addition, the frequency of the myocytes showing TUNEL positive was equal to or less than 1%. Accordingly, the absence of apoptosis findings with electron microscope did not mean that there was not apoptosis in myocytes, but observation area by electron microscope was too small.Subsequently, we performed to administrate sFas into the above heart failure rats via intraabdominal injection. However, we did not reach plasma sFas level to produce elevation of persistence of significance, and was not able to confirm improvement of heart failure. Because, turnover of plasma sFas is considered earlier unexpectedly in intraabdominal administration of sFas. Therefore, intraabdominal administration of sFas was not accepted for sFas expression extend over a long period of time. We concluded that gene therapy of sFas is necessary to realize continuous expression in myocardial tissue. Less