【作者】 杨大烜；

【导师】 李立环；

【作者基本信息】 中国协和医科大学 ， 心血管麻醉， 2007， 博士

【摘要】 目的:体外循环术后脑功能障碍是体外循环下心脏手术后的严重并发症。脑苷肌肽注射液是神经节苷脂和小分子多肽的复方制剂,神经节苷脂临床用于脑卒中,脊髓损伤等疾病的治疗,但对体外循环术后脑损伤的影响尚未见报道。因此,本研究观察体外循环下心脏瓣膜置换手术患者术中应用脑苷肌肽对血清S-100B蛋白、神经元特异性烯醇化酶（NSE）、细胞因子浓度以及脑氧代谢的影响,从而对其临床疗效进行相关评价。方法:40例CPB下心脏瓣膜置换术患者,术前无心内膜炎、糖尿病、高血压、高脂血症、神经系统、免疫系统和精神疾病病史,肺、肝、肾功能未见明显异常,心功能（NYHA）Ⅱ～Ⅲ级,随机分为脑苷肌肽组（A组）和对照组（B组）,每组20例。两组患者均在气管插管全身麻醉、中度低温和中度血液稀释体外循环下行心脏瓣膜置换术。麻醉后行桡动脉置管和右颈内静脉逆行置管至颈静脉球处。采用膜式氧合器行非搏动性灌注,动脉端装有微栓过滤器。灌注流量2.2～2.4L/（min.m²）,转流中维持平均动脉压50～80mmHg。冷血高钾停搏液停跳心脏,心包置冰保护心肌。CPB期间用α稳态处理酸碱血气状态,血流降温至鼻咽温30～31℃,降温速度为0.5～1℃/min,复温速度控制在每4～5min升高1℃。A组于麻醉诱导后静脉输注脑苷肌肽20ml（每毫升含神经节苷脂50μg、多肽3.2mg）,B组给予等容积生理盐水。观察给药前后血流动力学变化。分别于给药前（T1）、CPB结束（T2）及结束后2小时（T3）、6小时（T4）、24小时（T5）各时间点采集颈内静脉球部血,采用酶联免疫吸附法（ELISA）测定血清S-100B蛋白、神经元特异性烯醇化酶（NSE）、白介素—6（IL-6）、白介素-8（IL-8）和肿瘤坏死因子—α（TNF-α）浓度。此外,分别于给药前（t1）、CPB开始降温至鼻咽温33℃（t2）、心肌血运阻断20分钟（t3）、CPB复温至鼻咽温33℃（t4）、CPB结束（t5）以及手术结束（t6）各时间点测定并计算脑氧摄取率（COE）、颈静脉球部和桡动脉血血糖浓度差(G_a-jv)、以及颈静脉球部乳酸浓度（Lac）。结果:（1）两组患者给药前后血流动力学均无显著变化。（2）两组S-100B蛋白及NSE浓度在CPB后均显著升高,CPB后24小时（T5）S-100B浓度基本恢复至基础值水平（T1）,而NSE浓度仍高于基础值。组间比较显示B组S-100B浓度在T2、T3、T4和T5时间点均显著高于A组（P＜0.05）,B组NSE浓度在T2、T3和T4时间点亦显著高于A组（P＜0.05）。（3）两组IL-6、IL-8和TNF-α浓度在CPB后均显著升高,组间比较显示B组IL-6和IL-8浓度在T3、T4和T5时间点均显著高于A组（P＜0.05）,B组TNF-α浓度在T2、T3、T4和T5时间点均显著高于A组（P＜0.05）。（4）两组CPB降温及低温稳定阶段（t2和t3）脑氧摄取率和G_a-jv均显著低于基础值t1（P＜0.05）,并在t2点A组显著高于B组（P＜0.05）。两组Lac在CPB开始后进行性升高,CPB结束达到峰值,在t4、t5及t6点A组均显著低于B组（P＜0.05）。结论:脑苷肌肽可减少体外循环心脏瓣膜置换术病人S-100B蛋白、NSE以及细胞因子IL-6、IL-8和TNF-α的释放,提高体外循环心脏瓣膜置换术患者降温阶段脑氧摄取和脑糖利用,增加能量供应,减少乳酸生成,提示可能具有一定的脑保护作用。但本研究的结论尚需进一步的研究证实。更多还原

【Abstract】 Objective: Cerebral dysfunction remains to be a major source of morbidity after cardiac surgery. Cattle encephalon glycoside and ignotin injection is a compound of gangliosides which used to treat stroke and spinal injury. Its effect in cardiac surgery is uncertain. The aim of this study is to investigate the cerebral protective effects of cattle encephalon glycoside and ignotin injection in patients undergoing cardiac valve replacement with cardiopulmonary bypass （CPB）.Material and Methods: Forty patients undergoing cardiac valve replacement with CPB were randomly divided into two groups: cattle encephalon glycoside and ignotin injection group （group A, n = 20） and control group （group B, n = 20）. Patients who had medical history of endocarditis, diabetes mellitus, hypertension, hyperlipoidemia, neurologic disease, immunologic disease or mental disorder were excluded. In group A cattle encephalon glycoside and ignotin injection 20ml was given i.v. after induction of anesthesia. In group B normal saline was given instead of cattle encephalon glycoside and ignotin injection. The hemodynamic change was recorded. Blood samples were taken from jugular bulb after induction of anesthesia （T1）, discontinuation of CPB （T2）, 2h, 6h and 24 h （T3, T4 and T5） after discontinuation of CPB for determination of serum levels of S-100B protein , neuron specific enolase （NSE）, interleukin-6 （IL-6）, interleukin-8 （IL-8） and tumor necrosis factor-α（TNF-α）. Blood samples were also taken after induction of anesthesia （t1） , 33℃cooling （t2） , stable hypothermic duration （t3）, 33℃rewarming （t4） , discontinuation of CPB （t5） and discontinuation of operation （t6） for determination of arterial and jugular bulb blood gas, glucose and lactate （Lac） concentration. Utilization of glucose (G_a-jv) and cerebral extraction rate of oxygen （COE） were calculated.Results: （1） There was no hemodynamic change during the infusion of the drug in both groups. （2） Serum levels of S-100B protein and NSE were significantly increased after CPB. At time of T5, serum levels of S-100B protein decreased to near baseline （T1）, but serum levels of NSE remained high in both groups. At time of T2, T3, T4 and T5 , serum levels of S-100B protein were significantly higher in group B than in group A （P<0.05）. At time of T2, T3 and T4, serum levels of NSE were significantly higher in group B than in group A （P<0.05）. （3） Serum levels of IL-6, IL-8 and TNF-αwere significantly increased after CPB. At time of T3, T4 and T5, serum levels of IL-6 and IL-8 were significantly higher in group B than in group A （P<0.05）. At time of T2,T3,T4 and T5, serum levels of TNF-αwere significantly higher in group B than in group A . （4） At points t2 and t3, COE and G_a-jv in two groups were markedly lower than that at t1 （P<0.05）. At point t2, COE and G_a-jv were significantly higher in group A than in group B （P <0.05）. Serum levels of Lac increased after beginning of CPB and reached peak value at discontinuation of CPB, At point t4, t5and t6, serum levels of Lac were significantly lower in group A than in group B （P <0.05）.Conclusion: Cattle encephalon glycoside and ignotin injection could decrease the serum levels of S-100B protein, NSE, IL-6, IL-8 and TNF-α. It may increase COE and glucose utilization during cooling and decrease the serum level of lactate. It showed some degree of cerebral protective effect during cardiac valve replacement with CPB.更多还原