Distant effects of experimental renal ischemia/reperfusion injury
Distant effects of experimental renal ischemia/reperfusion injury
复制标题
DOI：
10.1097/01.asn.0000064946.94590.46
复制
发表时间：
2003-06-01
影响因子：
13.6
通讯作者：
Kelly, KJ
中科院分区：
文献类型：
--
作者：
Kelly, KJ
急性肾功能衰竭会导致严重的发病率和死亡率，但在临床情况下，肾功能衰竭并不是常见的死亡原因。我们之前已经报道了小鼠肾缺血后炎症介质肿瘤坏死因子-α(TNF-α)和白介素1(IL-1)的系统性增加。在本研究中，采用双侧肾缺血的动物模型来验证肾缺血时释放的细胞因子对其他器官系统有影响的假设。大鼠肾缺血后心脏组织中细胞间黏附分子-1mRNA、细胞间黏附分子-1mRNA、细胞间黏附分子-1mRNA、细胞间黏附分子-1mRNA和肿瘤坏死因子-α免疫反应性水平升高。伴随而来的是心脏、肝脏和肺中髓过氧化物酶活性的增加，髓过氧化物酶活性是组织白细胞渗透的一个指标。肾缺血后48h心脏功能改变包括超声心动图显示左心室舒张末内径、左心室收缩末期内径增大，左心室短轴缩短率降低。在短暂的肾缺血不足以引起氮质血症而不是双侧肾切除(导致严重的肾功能衰竭)后48h，也发现了心肌细胞凋亡的证据，这表明所观察到的细胞凋亡是肾脏缺血而不是尿毒症所必需的。还发现阻断肿瘤坏死因子-α的作用可限制心肌细胞的凋亡。肾脏缺血导致远期效应，心脏的改变可能是临床观察到的发病率和死亡率的重要原因。
Acute renal failure results in significant morbidity and mortality, yet renal failure is not the usual cause of death in the clinical situation. We have previously reported systemic increases in the inflammatory mediators tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) after renal ischemia in the mouse. In the present study, an animal model of bilateral renal ischemia was used to test the hypothesis that cytokines released with renal ischemia have effects on other organ systems. Increased levels of immunoreactive TNF-alpha and IL-1 and intercellular adhesion molecule-1 mRNA were found in the heart after renal ischemia in the rat. This was accompanied by increases in myeloperoxidase activity, an index of tissue leukocyte infiltration, in the heart as well as the liver and lung. Functional changes in the heart 48 h after renal ischemia included increases in left ventricular end diastolic diameter, left ventricular end systolic diameter, and decreased fractional shortening by echocardiography. Evidence of apoptosis of cardiac cells was also found 48 h after an abbreviated period of renal ischemia insufficient to induce azotemia but not bilateral nephrectomy (which resulted in significant renal failure), suggesting that renal ischemia but not uremia is necessary for the apoptosis observed. It was also found that blocking the action of TNF-alpha limited cardiac apoptosis. Renal ischemia results in distant effects and the alterations observed in the heart may be important in the morbidity and mortality observed clinically.