Autophagy is a lysosome-dependent degradative pathway which is characterized by cytoplasmic vacuolization. However,it is not just a simple degradative pathway. Research shows that autophagy is related to many diseases,such as neurodegenerative disease,malignant tumor,ageing,pathogenic microorganism infection,myocardial ischemia/reperfusion injury and so on. Autophagy exactly exists in myocardial ischemia/reperfusion injury,and it becomes a new research hotspot. This review will focus on the occurrence and development of autophagy and its role,signal transduction and research status in myocardial ischemia/reperfusion injury.
目的通过研究TNF-α拮抗剂enbrel(EB)对于一种确切的心衰动物模型的疗效验证这样一个假设:给予心衰大鼠慢性EB治疗能够减轻左心功能不全与左室重构并减低心肌IL-1β水平.方法我们对8只正常年龄对照的成年大鼠(对照组),8只异丙肾上腺素诱导的心衰大鼠(ISO组)以及8只经过EB治疗的异丙肾上腺素诱导的心肌损害大鼠(EB组)进行了心脏形态,收缩功能及细胞因子水平的测定.结果 EB组较ISO组左室舒张末期直径及收缩末期直径明显缩小而左室缩短率有明显提高(分别为9.2±0.3 mm vs 9.5±0.2 mm, 5.8±0.5 mm vs 6.5±0.3 mm, 0.37±0.03 vs 0.31±0.02, P<0.05,P<0.01,P<0.01),但两组间舒张末期左室后壁厚度无明显差异;EB组左室收缩末压,dp/dtmax明显高于(分别为104.8±4.6 mm Hg vs 98.4±4.9 mm Hg, 8395±940 mm Hg/s vs 6898±612 mm Hg, P<0.05,P<0.01)而左室舒张末期压力,dp/dtmin,左室舒张期时间常数显著低于ISO组(分别为3.8±0.6 mm Hg vs 7.1±0.8 mm Hg,-5963±475 mm Hg/s vs -5030±316 mm Hg/s,15.4±0.8 ms vs 21.3±1.4 ms, P<0.01).虽然EB组心脏收缩功能已有明显改善 ,但与对照组相比仍有明显差距.EB组的左室体重比较对照组明显增高(2.82±0.07 mg/g vs 2.28±0.08 mg/g, P<0.01),但与ISO 组无明显差异;EB组与ISO组血清TNF-α水平无明显差异,而在对照组则未能测出;EB组左室心肌组织中TNF-α水平显著高于对照组(757.6±46.8 pg/g vs 367.5±22.7 pg/g, P<0.01),但与ISO组无明显差别;EB 组左室心肌组织中IL-1β水平显著低于ISO组(356.2±28.5 pg/g vs 518.4±32.5 pg/g, P<0.05),而对照组则未能测出.在所有的大鼠血清中均未测到IL-1β.结论 (1)在致心衰剂量ISO造成心肌弥漫性坏死后,早期给予EB进行干预能够明显改善左室功能,这除了与其直接拮抗TNF-α的生物学作用外,可能部分地与心肌组织IL-1β表达水平下降有关.(2)EB具有减轻左室重构的作用,并且这种作用主要表现为对左室腔内径的影响.