【作者】 黄祥；

【导师】 方才；

【作者基本信息】 安徽医科大学 ， 麻醉学， 2010， 硕士

【摘要】 目的近年来,在肝脏保护研究领域兴起的药物预处理方法越来越受到重视,一些麻醉药预处理的肝保护作用已被研究证实。本研究采用右肝癌切除患者为研究对象,探讨七氟醚预处理对肝脏缺血/再灌注损伤的保护作用及其部分机制,为深入研究吸入性麻醉药对肝脏缺血/再灌注损伤的影响奠定一定的基础。方法40例择期行右肝癌切除术患者,ASA I或II级,术中经第一肝门阻断,血流阻断时间10～30min。随机分为2组:对照组(C组)和七氟醚预处理组(S组),每组20例。所有患者术前常规禁食6h,禁水2h。麻醉前30min肌肉注射咪达唑仑2mg和盐酸戊乙奎醚0.50mg。入室后开放左上肢静脉通路,常规监测心电图、平均动脉压(mean arterial pressure,MAP)、脉搏血氧饱和度(saturation of blood oxygen, SpO2)和脑电双频谱指数(bispectral index,BIS)。麻醉诱导:静脉注射咪达唑仑0.08～0.10mg/kg,依托咪酯0.20～0.30mg/kg,芬太尼8～10μg/kg及罗库溴铵0.60～0.80mg/kg,气管插管后行间歇正压机械通气(潮气量8～10ml/kg、呼吸频率12次/min、吸呼比1:1.5、氧流量2L/min),维持呼气末二氧化碳分压(end-tidal partial pressure of carbon dioxide,PETCO2)3.99～4.66kpa。左侧桡动脉穿刺置管用于监测MAP,右侧颈内静脉穿刺置管用于监测中心静脉压(central venous pressure ,CVP)。S组麻醉诱导插管后开启七氟醚挥发罐,调节吸入浓度和氧流量,使患者的呼气末七氟醚浓度迅速达到1.0最低肺泡有效浓度(minimal alveolar concentration, MAC)值,持续30min后洗出至肝门阻断开始;C组不用任何吸入性麻醉药。两组病人麻醉期间依脑电双频指数(BIS40～50)、血流动力学改变、手术刺激强度间断静注芬太尼、咪达唑仑、维库溴铵维持麻醉深度。术中静脉输注乳酸钠林格液和羟乙基淀粉130/0.4氯化钠注射液10～12ml/(kg·h),补充失血和失液量,晶胶比1:1,必要时注射尼卡地平或去氧肾上腺素,维持心率(Heart rate ,HR)和MAP稳定,使其波动幅度不超过基础值20%,当Hb<80g/L或Hct<24%时,按需输注红细胞悬液。于麻醉诱导前(T0)、肝门阻断即刻(T1)、肝门开放即刻(T2)、缺血/再灌注1h(T3)、6h(T4)、24h(T5)测血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、乳酸脱氢酶(LDH)、TNF-α、IL-1的含量以及缺血/再灌注1h肝组织匀浆中丙二醛(MDA)含量和超氧化物岐化酶(SOD)活性,并行肝组织病理学观察。结果与麻醉诱导前比较,两组患者于肝门开放即刻、缺血/再灌注后1h、6h、24h血清ALT、AST、LDH、TNF-α、IL-1浓度均显著增加(P<0.05);与C组比较,S组于肝门开放即刻、缺血/再灌注后相应各时点血清ALT、AST、LDH、TNF-α、IL-1浓度均降低(P<0.05);缺血/再灌注后1h肝组织匀浆MDA含量减少,SOD活性增加(P<0.05),肝组织病理学损伤减轻。结论1.七氟醚预处理对右肝切除患者肝脏缺血/再灌注损伤有保护作用。2.其机制可能:(1)与其抑制氧自由基生成,减少脂质过氧化有关;(2)与其抑制炎症反应,减少炎性因子生成有关。更多还原

【Abstract】 Objective In recent years, the rise of research in the liver to protect the drug pretreatment increased attention, some of the liver protective effect of anesthetic preconditioning have been studies confirmed. In this study, patients with right liver resection as the research object of sevoflurane preconditioning on hepatic ischemia-reperfusion injury in patients and its part of the mechanism for in-depth study of inhalational anesthetics on hepatic ischemia-reperfusion injury in rats lay a certain foundation.Methods 40 cases of elective liver resection in patients with the right line, ASA I or II level, surgery through the first portal triad clamping, blood flow occlusion time 10 ~ 30min. Were randomly divided into two groups: control group (C group) and sevoflurane preconditioning group (S group), 20 patients in each group. All patients routine preoperative fasting 6h, water deprivation 2h. 30min before anesthesia intramuscular midazolam 2mg and hydrochloric acid penehyclidine 0.5mg. After the break-open the left upper extremity venous access, routine monitoring of ECG, mean arterial pressure (MAP), pulse oxygen saturation (SpO2) and the bispectral index. Induction of anesthesia: intravenous injection of midazolam 0.08 ~ 0.10mg/kg, etomidate 0.2 ~ 0.3mg/kg, fentanyl 8 ~ 10μg/kg and rocuronium 0.6 ~ 0.8mg/kg, after intubation OK intermittent positive pressure mechanical ventilation (tidal volume of 8 ~ 10ml/kg, respiratory rate 12 times/min, suction call ratio 1:1.5, oxygen flow 2L/min), to maintain end-expiratory carbon dioxide (PETCO2) 3.99 ~ 4.66kpa。The left radial artery catheterization for monitoring the MAP, the right internal jugular vein catheterization for blood collection. S group, after anesthesia induction and tracheal intubation to open sevoflurane vaporizer, regulating the concentration and oxygen inhalation flow rate, so that patients with end-tidal sevoflurane concentration quickly reached 1.0MAC value, and continued to wash out after 30min to Pringle started; C group without any inhaled anesthetics. Two groups of patients under anesthesia during the bispectral index (BIS40-50), hemodynamic changes, surgical stimulus intensity intermittent intravenous fentanyl, midazolam, vecuronium to maintain depth of anesthesia. Intraoperative intravenous infusion of lactated Ringer’s solution and hydroxyethyl starch 130/0.4 and sodium chloride injection 10 ~ 12ml/ (kg·h), additional blood loss and loss of fluid volume, crystal-cement ratio of 1:1, if necessary, injection of Nepal Card horizon or phenylephrine to maintain a stable HR and MAP to baseline fluctuations of no more than 20%, when Hb <80g /L or Hct <24%, the on-demand infusion of red blood cell suspension. Before induction of anesthesia (T0), Pringle immediately (T1), hepatic portal, opening up instantly (T2), ischemia/reperfusion 1h (T3), 6h (T4), 24h (T5) Measurement of serum alanine aminotransferase ( ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), TNF-α, IL-1 levels, as well as ischemia/reperfusion 1h liver tissue homogenate malondialdehyde (MDA) content and superoxide dismutase dismutase (SOD) activity, liver histopathology observed in parallel.Result With the induction of anesthesia comparison, the two groups in the hepatic portal open instantly, ischemia / reperfusion after 1h,6 h, 24h of serum ALT, AST, LDH, TNF-α, IL-1 levels were significantly increased (P <0.05); compared with the C group, S group in the hepatic portal open instantly, ischemia/reperfusion the corresponding time points of serum ALT, AST, LDH, TNF-α, IL-1 levels were lower (P<0.05); ischemia/re - 1h after reperfusion of liver homogenate MDA content decreased, SOD activity increased (P <0.05), liver Conclusion1. Sevoflurane preconditioning can protect right liver operation from ischemia reperfusion injury.2. The protective mechanisms maybe(1) related to reduceing the release of oxyradical and inhibiting the lipid peroxidation;(2) related to reduceing inflammatory response and inhibition to reduce the generation of inflammatory factors.更多还原