柳叶刀：华中科大找到术后并发症相关基因

　　

生物通报道：毛细血管渗漏综合征（Capillary leak syndrome）是体外循环（cardiopulmonary bypass）手术后的并发症之一，通俗地说就是血管里的水向外渗透，表现为严重的水肿和器官衰竭，患者死亡率达3％，在全世界儿童身上的发病率大约为4-37％。医疗界一直没有找到毛细血管渗漏综合征的发病机理和解决办法。

来自华中科技大学同济医学院协和医院的研究人员发现了C4A基因与毛细血管渗漏综合征有密切的关系，文章发表在2005年8月的世界著名医学杂志《柳叶刀》（Lancet）上。研究发现，体内缺少C4A基因的患者，将有极大可能体外循环后患上毛细血管渗漏综合征。之前由于不知道该病的发病原因，只能在疾病发生后进行对症治疗，治疗效果较差，死亡率高。文章的第一作者张诗海教授表示：由于知道了原因，在手术过程中，对缺乏C4A基因的患者补充富含C4A基因的血浆能够降低发病率，研究表明可降低97％。

作者介绍：

张诗海 
职称职务： 副教授，副主任医师，硕士生导师 
简 介： 主要从事麻醉学和疼痛治疗的临床和研究工作，临床经验丰富，擅长于神经外科、心血管外科、腔镜外科的临床麻醉以及危重患者的治疗处理。承担多项国家和省、市级研究课题，其中“体外循环常见并发症基因芯片的构建”获国家自然科学基金。科研成果丰富，在国际著名学术刊物Anesthesiology和Acta Pharmacologica Sinica上发表学术论文多篇，并参与了《麻醉学基础》、《临床麻醉学》、《急诊麻醉学》、《颅底外科学》等专业书籍的编写。

原文：Lancet. 2005 Aug 13-19;366(9485):556-62. Related Articles, Links 

Capillary leak syndrome in children with C4A-deficiency undergoing cardiac surgery with cardiopulmonary bypass: a double-blind, randomised controlled study.

Zhang S, Wang S, Li Q, Yao S, Zeng B, Ziegelstein RC, Hu Q.

Department of Anaesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

BACKGROUND: Capillary leak syndrome is a life-threatening complication after cardiopulmonary bypass (CPB), with an incidence of about 4-37% in children worldwide. On the basis of previous results, we undertook a randomised controlled study to investigate the priming with plasma rich in the C4A isotype of complement component 4 on the incidence of capillary leak syndrome in children with C4A deficiency. METHODS: In a hospital in Wuhan, China, we randomly assigned 116 neonates, infants, and children lacking complement component C4A to receive C4A-free or C4A-rich plasma priming (n=58 each, 20 mL/kg). The primary outcome was capillary leak syndrome, identified as an increased transvascular escape rate of Evans blue dye from plasma. Concentrations of activated complement components C4 and C3, inflammatory mediators interleukin 6, interleukin 8, tumour necrosis factor (TNF) alpha, plasma protein, and PaO2/F(I)O2 ratios (ratio of the partial arterial pressure of oxygen to the fractional concentration of oxygen in inspired air) were measured before and 4 h after CPB. Analysis was by intention to treat. FINDINGS: Three (5%) patients given C4A-rich plasma priming had capillary leak syndrome compared with 56 (97%) given C4A-free plasma (p<0.0001). At 4 h after CPB, activated C4, interleukin 6, interleukin 8, and TNFalpha concentrations were higher, whereas PaO2/F(I)O2 ratios and plasma protein concentrations were significantly lower in the C4A-free group than changes in the C4A-rich group. Activated C3 rose equally in both groups. Activated C4 significantly correlated with interleukin 6, interleukin 8, and TNFalpha concentrations; PaO2/F(I)O2 ratios; and the escape rate of Evans blue dye at 4 h after CPB. Two patients in the C4A-free group died of respiratory and renal failure on day 3 after CPB. INTERPRETATION: In paediatric patients with C4A deficiency, C4A-rich plasma priming reduces the incidence of CPB-related capillary leak syndrome by blocking the activated C4 increase and attenuating the systemic inflammatory response after CPB.