Protective effects of relaxin in ischemia/reperfusion-induced intestinal injury due to splanchnic artery occlusion
Protective effects of relaxin in ischemia/reperfusion-induced intestinal injury due to splanchnic artery occlusion
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DOI：
10.1038/sj.bjp.0706811
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发表时间：
2006-08-01
影响因子：
7.3
通讯作者：
Bani, Daniele
中科院分区：
文献类型：
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作者：
Masini, Emanuela;Cuzzocrea, Salvatore;Bani, Daniele
1.内脏动脉阻断（SAO）后再灌注可引起内皮细胞损伤和炎症反应，从而导致休克的病理生理过程。我们研究了松弛素（RLX）对内脏动脉闭塞和再灌注（SAO/R）诱导的内脏损伤大鼠的影响，已知松弛素（RLX）可以保护心脏缺血/再灌注的有害影响。2 RLX（30 ng kg（-1），再灌注前15分钟）显着降低SAO/R引起的血压下降和高死亡率。RLX还减少回肠中的组织病理学变化、白细胞浸润（髓过氧化物酶）和内皮细胞粘附分子的表达。RLX抵消了自由基介导的组织损伤，这是通过组织过氧化和硝化产物（丙二醛、硝基酪氨酸）水平、DNA损伤标记物（8-羟基-2 '-脱氧鸟苷、聚ADP核糖基化DNA）和组织抗氧化酶（超氧化物歧化酶）消耗的显著降低来判断的。结果，RLX导致回肠细胞凋亡减少（半胱天冬酶3，末端脱氧核苷酸转移酶介导的UTP末端标记）。RLX的作用似乎是特异性的，因为灭活的RLX替代生物活性激素没有效果。3总之，这些结果表明，RLX在SAO/R诱导的内脏损伤中发挥明确的保护作用，可能是由于内皮保护、减少白细胞募集和阻碍自由基介导的组织损伤导致细胞死亡、致命并发症和高死亡率。因此，RLX可用于治疗肠缺血。
1 Splanchnic artery occlusion (SAO) followed by reperfusion causes endothelial injury and inflammation which contribute to the pathophysiology of shock. We investigated the effects of relaxin (RLX), known to afford protection against the deleterious effects of cardiac ischemia/ reperfusion, given to rats subjected to splanchnic artery occlusion and reperfusion (SAO/R)-induced splanchnic injury.2 RLX (30 ng kg(-1), 15 min. before reperfusion) significantly reduced the drop of blood pressure and high mortality rate caused by SAO/R. RLX also reduced histopathological changes, leukocyte infiltration (myeloperoxidase) and expression of endothelial cell adhesion molecules in the ileum. RLX counteracted free radical-mediated tissue injury, as judged by significant decrease in the tissue levels of peroxidation and nitration products (malondialdehyde, nitrotyrosine), DNA damage markers (8-hydroxy-2'-deoxyguanosine, poly-ADP-ribosylated DNA) and consumption of tissue antioxidant enzymes ( superoxide dismutase). As a result, RLX led to a reduction of ileal cell apoptosis (caspase 3, terminal deoxynucleotidyltransferase-mediated UTP end labeling). The effects of RLX appear specific, as inactivated RLX substituted for the bioactive hormone had no effects.3 In conclusion, these results show that RLX exerts a clear-cut protective effect in SAO/R-induced splanchnic injury, likely due to endothelial protection, decreased leukocyte recruitment and hindrance of free radical-mediated tissue injury leading to cell death, lethal complications and high mortality rate. Thus, RLX could be used therapeutically in intestinal ischemia.