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体外循环心内直视手术围术期乌司他丁对血浆S100β蛋白及TNF表达的影响
[Abstract] Objective To investigate the effect of ulinastatin on expression of S100βprotein and TNF-a in patients undergoing open-heart surgery with cardiopulmonary bypass. Methods 30 adult patients undergoing elective open-heart surgery with cardiopulmonary bypass were randomly allocated to two groups (n＝15 each): ulinastation (U) and control (C) group. In group U, the patients received ulinastain 10 000U/kg after induction of anesthesia and before CPB. Another ulinastain 10 000U/kg was added to the priming solution at the beginning of the CPB. In group C the patients received normal saline instead of ulinastain. Blood samples were taken from internal jugular vein 15min after initiation of CPB (T1), when discontinuation of CPB (T2), 2h (T3) and 24h (T4) after discontinuation of CPB for determination of plasma S100β protein and TNF-a levels. Results Plasma levels of S100β protein and TNF-a in group U were significantly lower than those in group C at T2 ( P＜0.01） and T3 ( P＜0.05）. There were no difference between in both groups at T1 and T4 ( P＞0.05 ). The plasma level of S100β protein significantly increased at T2-4 as compared to the baseline value at T [Key words] Cardiopulmonary bypass; Trypsin inhibitors; S100 protein; Tumor necrosis factor 目前体外循环心脏直视手术后因神经系统缺陷引起的死亡率明显上升，而体外循环对中枢神经系统损伤是心脏手术所造成的非心血管致死性并发症的重要原因。研究表明，3%～6%体外循环心脏手术后的病人存在明显脑功能缺陷,通过神经精神检查发现脑损伤的发生率高达60%～70% [1-2]。 乌司他丁是一种尿蛋白酶抑制剂，能有效、广谱抑制多种蛋白酶以及机体炎症因子的释放，保护机体重要脏器的功能。近年来，有报导乌司他丁对CPB期肾功能、肺功能、心肌缺血再灌注以及凝血功能均有一定的影响[3-4]，而对CPB心内直视手术围术期脑损伤的影响如何尚有待研究。本研究通过观察CPB后不同时间点脑损伤的血浆敏感标志物S100β蛋白、TNF-a的水平，探讨乌司他丁对CPB心内直视手术所致脑损伤的影响及其机制。 1资料与方法 1.1病例选择与分组 择期体外循环心内直视术病人30例，男11例，女19例ASAⅡ或Ⅲ级，年龄18~65岁，体重43~ 1.2麻醉和处理 两组病人麻醉前30 min肌注吗啡5 mg、咪达唑仑3~5 mg及东莨菪碱0.3 mg。入室后连接DATEX-OHMEDA S/5监护仪监测心电图（ECG），脉搏血氧饱和度（SpO2）, 局麻下桡动脉穿刺置管测平均动脉压（MAP）,右颈内静脉置管测中心静脉压(CVP)。依次静脉注射咪达唑仑0.1 mg.kg-1, 芬太尼5~7 μg.kg-1及维库溴铵0.15mg.kg-1行麻醉诱导气管插管，术中连接NARKOMED GS麻醉机作控制呼吸，维持PETCO2 35~40 mmHg，术中以芬太尼5μg.kg-1.h-1、丙泊酚5mg.kg-1.h-1和维库溴铵0.12mg.kg-1.h-1维持麻醉。肝素化后建立CPB，使用德国Stockert SⅢ型体外循环机器和意大利Didecd鼓泡式人工肺。转流期间维持鼻咽温 U组麻醉诱导后、体外循环前将乌司他丁（批号：02050401, 广东天普生化医药股份有限公司）10 000 U/kg溶于50ml生理盐水中微量泵输入，CPB开始时再将乌司他丁10 000 U/kg加入体外循环机预充液中；C组用等容量的生理盐水。 1.3检测指标与处理 分别于CPB开始后15min（T1）、CPB结束时（T2）、CPB结束后2h（T3）、CPB结束后24h（T4）时采颈内静脉血4ml，经 1.4统计学处理 采用SPSS13.0 for Windows统计软件进行统计分析，计量资料以均数±标准差（±s）表示，组间比较采用成组设计t检验，组内比较采用双因素方差分析；计数资料采用卡方检验。P＜0.05表示差异有统计学意义。 2结 果 2.1一般情况的比较 两组病人年龄、性别构成比、体重、手术种类构成比、CPB时间及主动脉阻断时间的差异均无统计学意义（P＞0.05）(见表1)。
2.2两组S100β蛋白浓度的比较 U组S100βT2时点明显低于C组 （P＜0.01）；T3时点低于C组（P＜0.05）；而T1和T4时点两组间比较差别无统计学意义（P＞0.05）。两组T2、T3、T4时S100β蛋白浓度均高于T1（P＜0.01）(见表2)。
2.3两组细胞因子TNF-a水平的比较 U组TNF-a浓度T2时点明显低于C组 （P＜0.01），T3时点低于C组（P＜0.05）；而T1和T4时点两组间比较差别无统计学意义（P＞0.05）。C组T2、T3时TNF-a水平明显高于T1（p＜0.01），U组各时点TNF-a浓度比较差别均无统计学意义（P＞0.05）(见表3)。
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