长效局麻药减轻FMLP诱导的大鼠急性肺损伤的作用  

作　　者：Marcus T. Schley, MD Matthias Casutt, MD Christoph Haberthar, PhD Martin Dusch, MD Roman Rukwied, PhD Martin Schmelz, MD, PhD Joachim Schmeck, MD,PhD Guido K. Schupfer, MD, PhD , Christoph J, Konrad, MD, PhD 徐妍君(译) 李士通(校) 

机构地区：[1]Department of Anaesthesiology and Operative Intensive Care Medicine, Kantonsspital, Lucerne, Switzerland [2]Department of Anaesthesiology and Intensive Care Medicine, University of Heidelberg, Heidelberg, Germany [3]Department of Anaesthesiology, University of Mainz, Mainz, Germany [4]不详

出　　处：《麻醉与镇痛》2012年第3期52-57,共6页Anesthesia & Analgesia

摘　　要：背景内皮素-1（endothelin-1，ET-1）可介导肺部疾病，是一个强有力的血管收缩药。与血栓素A2一起参与了肺水肿的形成。利多卡因和甲哌卡因可以缓解肺动脉压的升高以及肺水肿的进展。我们利用增加肺动脉压、促使ET—1释放的实验模型验证普鲁卡因、布比卡因、罗哌卡因的作用。方法用Krebs-Henseleit羟乙基淀粉缓冲液灌注大鼠离体肺脏，测量肺动脉压及肺脏质量，加入10^-1-10^7mg／kg浓度的布比卡因、罗哌卡因、普鲁卡因，用免疫酶标技术检测ET-1水平，放射免疫法检验血栓素A2水平，用N-甲酰-甲硫氨酰．亮氨酰苯丙氨酸（FMLP）来激活人多形核中性粒细胞。结果与对照组（P〈0．05）相比，治疗组布比卡因、罗哌卡因、普鲁卡因明显减轻了肺动脉压的升高（P〈0．05），导致肺脏质量的减轻。除了普鲁卡因，在剂量为10^-3-10^-6mg／kg的范围中，长效局麻药布比卡因、罗哌卡因（P〈0．05）降低了ET-1的水平，降低炎症发生率，且不影响肺结构。结论布比卡因、罗哌卡因能缓解FMLP诱导的肺动脉压升高，减轻肺水肿，减少ET-1释放。利多卡因和甲哌卡因能更有效地缓解肺动脉压升高以及肺水肿形成，但是长效局麻药能通过抑制ET-1的释放增强抗炎能力。BACKGROUND： Endothelin-1 （ET-1） is a mediator of lung diseases and a potent pulmonary vasoconstrictor. In addition to thromboxane A2, it participates in the formation of lung edema. Both lidocaine and mepivacaine attenuate the increase of pulmonary arterial pressure （PAP） and lung edema development. We examined the effects of procaine, bupivacaine~ and ropivacaine on experimentally evoked PAP increase and ET-1 release. METHODS： PAP and lung weight were measured in isolated rat lungs during perfusion with Krebs-Henseleit hydroxyethyl starch buffer. Bupivacaine, ropivacaine, or procaine was added to the solution at concentrations of 10^-2 - 10^-7 mg/kg. ET-I levels were measured in the perfusate by enzyme- immunoassay, and thromboxane A2 levels were assayed by radioimmunoassay. N-formyl-L-leucinemethionyl-L-phenylalanine was used to activate human polymorphonudear neutrophils. RESULTS： Bupivacaine, ropivacaine, and procaine significantly attenuated increases of PAP （P 〈 0. 05） and resulted in a reduction of lung weight in these treatment groups compared with the sham group （P 〈 0. 05）. The long-acting anesthetics bupivacaine and ropivacaine （P 〈 0.05）, but not procaine, reduced ET-1 levels, produced low inflammation rates, and did not affect lung structures at doses from 10^-3 to 10^-6 mg/kg. CONCLUSION： Bupivacaine and ropivacaine attenuated N-formyl-L-leudne-methionyll-phenylalanine-induced PAP, reduced lung edema, and diminished ET-1 release. Lidocaine and mepivacaine are more effective in reducing PAP and edema formation, but long-acting local anesthetics also inhibit ET-1 depletion and therefore have increased anti-inflammatory properties.

关 键 词：急性肺损伤 长效局麻药 FMLP 减轻 大鼠 ET-1水平 多形核中性粒细胞 布比卡因 

分 类 号：R563[医药卫生—呼吸系统]