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浙江大学学报（医学版）
浙江大学学报（医学版）  2015, Vol. 44 Issue (5): 532-538    DOI: 10.3785/j.issn.1008-9292.2015.09.10
原著     
乌司他丁对冠状动脉搭桥术后患者认知功能障碍的影响
葛亚力1, 史宏伟1, 朱雯霏1, 马正良2, 魏海燕1, 顾小萍2, 鲍红光1
1. 南京医科大学附属南京医院麻醉科, 江苏南京 210006;
2. 南京医科大学鼓楼临床医学院, 江苏南京 210008
Effects of ulinastatin on cognitive function in patients with coronary artery bypass grafting
GE Ya-li1, SHI Hong-wei1, ZHU Wen-fei1, MA Zheng-liang2, WEI Hai-yan1, GU Xiao-ping2, Bao Hong-guang1
1. Department of Anesthesiology, Affiliated Nanjing Hospital, Nanjing Medical University, Nanjing 210006, China;
2. Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing 210008, China
全文: PDF(833 KB)  
摘要: 

目的:探讨不同剂量乌司他丁对冠状动脉搭桥术患者术后认知功能障碍的影响及其可能的作用机制。方法:选择2013年1月至2014年6月在南京医科大学附属南京医院就诊择期行冠状动脉搭桥术的老年患者127例,分为三组:大剂量乌司他丁组(1.6万U/kg)、小剂量乌司他丁组(0.8万U/kg)和对照组(等容量的生理盐水)。所有患者在手术当日和次日晨8时测血浆皮质醇浓度,并在术前、开胸、术毕、术后6 h和术后24 h分别检测IL-6、IL-10、TNF-α和S100β蛋白水平。术前1 d、术后1周和3个月分别应用精神神经测试组合量表评估患者认知功能的变化判定有无术后认知功能障碍,计算各组患者术后认知功能障碍的发生率,并且比较术后1周是否发生术后认知功能障碍患者S100β蛋白水平。结果:最终93例患者完成研究,三组患者一般资料比较差异均无统计学意义(均P>0.05)。与术前相比较,对照组患者术后24 h血浆皮质醇浓度升高明显(P<0.01),且大剂量和小剂量乌司他丁组患者术后血浆皮质醇浓度均较对照组低(均P<0.01);三组患者术毕、术后6 h和24 h血浆IL-6、IL-10、TNF-α水平及S100β蛋白水平均高于术前(均P<0.05);大剂量和小剂量乌司他丁组患者在术毕、术后6 h和24 h血浆IL-6、TNF-α水平浇以及在术后6 h S100β蛋白水平均比相对应时间点的对照组患者降低(均P<0.05),但大剂量和小剂量乌司他丁组患者组间差异无统计学意义(P>0.05)。大剂量和小剂量乌司他丁组患者术后1周认知功能障碍发生率(25.8%和23.3%)均低于对照组(50.0%),差异有统计学意义(均P<0.05);而大剂量和小剂量乌司他丁组术后3个月的术后认知功能障碍发生率(12.9%和16.7%)与对照组(28.1%)比较,差异均无统计学意义(P>0.05)。术后认知功能障碍组(n=31)在术后24 h血清S100β蛋白水平高于非术后认知功能障碍组(n=62),其差异具有统计学意义(P<0.05)。结论:乌司他丁可降低冠状动脉搭桥术患者术后1周的术后认知功能障碍的发生率,其机制可能与减轻炎性反应及脑损伤有关。
关键词 ： 冠状动脉分流术/副作用,  神经系统疾病/病因学,  白细胞介素/血液,  糖蛋白类/治疗应用,  肿瘤坏死因子α/血液,  认知障碍    
Abstract：

Objective:To investigate the effects of ulinastatin(UTI) on postoperative cognitive function in patients undergoing coronary artery bypass grafting. Methods:One hundred and twenty-seven patients undergoing elective coronary artery bypass surgery were randomly divided into three groups:high-dose UTI group(16000 U/kg i.v.), low-dose UTI group(8000 U/kg i.v.) and control group(normal saline). The levels of plasma cortisol were measured before and one day after surgery. The level of IL-6, IL-10, TNF-α and S100β were measured before operation(T0), at open chest(T1), end of operation(T2), 6 h(T3)and 24 h(T4) after operation. A neuropsychological test scale was to evaluate the cognitive function 1 day before operation, 1 week and 3 months after operation. Results:Ninety-three patients completed the study. There was no significant difference in general information of patients among three groups(P>0.05). The level of plasma cortisol one day after operation was significantly higher than that before operation in control group(P<0.01). The levels of plasma cortisol in high-dose UTI group and low-dose UTI group were lower than that of control group(P<0.01). In all groups, the level of plasma IL-6, IL-10, TNF-α and S100B increased remarkably at T2, T3, T4 compared to those at T0(all P<0.05). The level of plasma IL-6, TNF-α(at T2, T3, T4)and S100β(at T3)in high-dose UTI group and low-dose UTI group were all lower than those of control group(P<0.05),while there were no significant differences between high-dose UTI group and low-dose UTI group(P>0.05). The incidence of postoperative cognitive dysfunction in POCD 1 week after operation in high-dose UTI and low-dose UTI groups(25.8% and 23.3%)was lower than that in control group(50.0%), while there were no significant difference 1 month after operation between high-dose UTI group(12.9%) or low-dose UTI group(16.7%)and control group(28.1%). The level of plasma S100β at T2 of POCD patients(n=31)was higher than that of non-POCD group(n=62)(P<0.05). Conclusion:Ulinastatin can reduce the incidence of postoperative cognitive dusfunction 1 week after coronary artery bypass surgery, which might be associated with inhibition of inflammation and S100β expression.
Key words： Coronary artery bypass/adverse effects    Nervous system diseases/etiology    Interleukin/blood    Glycoproteins/therapeutic use    Tumor necrosis factor-alpha/blood    Cognition disorders
收稿日期: 2015-03-17 出版日期: 2015-11-12
CLC:  R453  
基金资助:

南京市医学科技发展专项资金项目(YKK13115)
通讯作者: 马正良(1964-),男,博士,教授,博士生导师,主要从事疼痛信号的转导与调控及脏器保护研究;E-mail:mazhengliang1964@nju.edu.cn;http://orcid.org/0000-0003-0417-0894     E-mail: mazhengliang1964@nju.edu.cn
作者简介: 葛亚力(1971-),男,博士,副主任医师,主要从事心血管麻醉与监测;E-mail:ge_yl@163.com;http://orcid.org/0000-0001-8417-1672
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引用本文:

葛亚力, 史宏伟, 朱雯霏, 马正良, 魏海燕, 顾小萍, 鲍红光. 乌司他丁对冠状动脉搭桥术后患者认知功能障碍的影响[J]. 浙江大学学报（医学版）, 2015, 44(5): 532-538.
GE Ya-li, SHI Hong-wei, ZHU Wen-fei, MA Zheng-liang, WEI Hai-yan, GU Xiao-ping, Bao Hong-guang. Effects of ulinastatin on cognitive function in patients with coronary artery bypass grafting. Journal of ZheJiang University(Medical Science), 2015, 44(5): 532-538.

链接本文:

http://www.zjujournals.com/xueshu/med/CN/10.3785/j.issn.1008-9292.2015.09.10      或      http://www.zjujournals.com/xueshu/med/CN/Y2015/V44/I5/532

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