急性心不全に対する補助循環治療成績を改善する新規グレリン皮下投与法の開発研究

开发新型皮下生长素释放肽给药方法以改善急性心力衰竭辅助循环治疗的效果

基本信息

批准号：
16F16118
负责人：
巽英介
金额：
$ 1.47万
依托单位：
National Cardiovascular Center Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for JSPS Fellows
财政年份：
2016
资助国家：
日本
起止时间：
2016-04-22 至 2018-03-31
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16F16118/
关键词：
Ghrelin inflammation organ damage oxidative stress cardiopulmonary bypass ghrelin cardiopulmonary support

项目摘要

Cardiopulmonary bypass (CPB) induced inflammation significantly contributes to the development of postoperative complications, including respiratory failure, myocardial, renal and neurological dysfunction and ultimately leads to multiple organ failure. Ghrelin is a small endogenous peptide with wide ranging physiological effects on metabolism and cardiovascular regulation. We investigated the protective effects of ghrelin against the CPB-induced inflammatory reactions, oxidative stress and acute organ damage. Adult male rats were subjected to CPB for 4 hrs and randomly received vehicle (n=6) or a bolus of ghrelin (150 microgram/kg, sc, n=6). Rats were euthanized and heart, lung, liver, kidney and brain samples were harvested for histopathology. Blood samples were taken before CPB, after 2 hrs and 4 hrs of CPB. We measured the plasma levels of cytokines, catecholamines and organ damage markers and glutathione concentrations. CPB-induced leucocytosis with increased plasma levels of TNF-α, IL-6 indicating an inflammatory response. Our study results suggest that even though ghrelin only partially inhibited the large CPB induced increase in catecholamines and organ macrophage infiltration, it reduced oxidative stress and subsequent cell damage (Sukumaran et al., 2018). Administration of ghrelin might provide an effective co-treatment for reducing widespread CPB-induced organ injury.

心肺旁路（CPB）诱导的炎症显着有助于术后并发症的发展，包括呼吸衰竭，心肌，肾脏和神经功能障碍，并最终导致多器官衰竭。生长素是一种小的内源性肽，其物理对代谢和心血管调节的影响很大。我们研究了生长素蛋白对CPB诱导的炎症反应，氧化应激和急性器官损伤的保护作用。将成年雄性大鼠接受CPB 4小时，然后随机接收的车辆（n = 6）或Ghrelin的推注（150微克/kg，sc，n = 6）。将大鼠安乐死，心脏，肺，肝脏，肾脏和大脑样本进行组织病理学。在CPB之前，在2小时和4小时CPB之前取血样品。我们测量了细胞因子，儿茶酚胺和器官损伤标记和谷胱甘肽浓度的血浆水平。 CPB诱导的白细胞增多症，血浆水平升高的TNF-α，IL-6表明炎症反应。我们的研究结果表明，即使生长素素仅部分抑制了CPB大的CPB诱导的儿茶酚胺和器官巨噬细胞浸润的增加，但它降低了氧化应激和随后的细胞损伤（Sukumaran等，2018）。生长素蛋白的给药可能提供有效的共同处理，以减少CPB诱导的器官损伤。