麻醉药对中性粒细胞呼吸爆发功能的影响

中性粒细胞是炎症反应的重要效应细胞，在机体起消灭病原体和组织损伤双重作用。呼吸爆发是中性粒细胞发挥其作用的重要机制之一。现就麻醉药物对中性粒细胞呼吸爆发功能影响及其机制研究作一综述。     

氯胺酮和丙泊酚对中性粒细胞呼吸爆发功能的影响

目的：研究氯胺酮、丙泊酚在体外对佛波酯（PMA）刺激后人中性粒细胞（PMN）呼吸爆发功能的影响。方法：采健康人静脉血（n=5），分为对照组（C组），氟胺酮1、2、3组（K1、K2、K3组），丙泊酚1、2、3组（P1、P2、P3组），氯胺酮、丙泊酚终浓度分别为0、3、30、300μg/ml和5、50、500μg/ml，以全血法测定PMN呼吸爆发强度（DHR标记，流式细胞法）。结果：氯胺酮、丙泊酚均可剂量依赖性地抑制PMA刺激后PMN的呼吸爆发强度，P2、K3、P3组呼吸爆发强度均非常显著地低于C组（P＜0．01），丙泊酚的抑制效应又强于对应浓度的的氯胺酮（P2 vs K2,P＜0．05；P3 vs K3,P＜0．01）。结论：氯胺酮、丙泊酚抑制PMN呼吸爆发的作用，可能会影响到围术期病人的免疫状态，值得临床注意。     

术中保温对肺癌根治术患者中性粒细胞呼吸爆发的影响

目的探讨术中保温对肺癌根治术患者中性粒细胞（PMNs）呼吸爆发的影响。方法32例全麻下行肺癌根治术患者，ASAⅡ或Ⅲ级，随机分为2组（n=16）：对照组（C组）和保温组（W组）。C组术中仅以毛毯等常规保温措施保温；W组还使用加温毯和输液加温器保温，以维持术中核心体温不低于基础值。静脉注射芬太尼、咪达唑仑、异丙酚和罗库溴铵行麻醉诱导后气管插管，术中吸入异氟醚和氧化亚氮维持麻醉。于术前（基础值）、术中（关胸前冲洗胸腔后即刻）和术毕（缝皮结束）采集外周静脉血，测定血常规、PMNs活化率及其活性氧（ROS）产量。结果与术前相比，2组术中和术毕时WBC计数及PMNs百分比均升高（P〈0．05），2组间WBC计数和PMNs百分比差异无统计学意义。在刺激状态下（加入佛波酯）：与术前相比，2组术中、术毕时PMNs活化率均升高，W组术毕时ROS产量升高（P〈0．05），W组术毕时ROS产量高于C组（P〈0．05）；在静态下（加入磷酸盐缓冲液）：与术前相比，C组术中PMNs活化率和术中、术毕时ROS产量均降低（P〈0．05），W组术中PMNs活化率、术中及术毕ROS产量均高于C组（P〈0．05）。结论肺癌根治术中保温可保持静态下活化PMNs的数量和ROS产量，并增强刺激状态下PMNs的ROS产量，但对活化的PMNs数量无影响。     

不同细胞分离制备方法下异丙酚对中性粒细胞呼吸爆发作用的影响

目的 在两种中性粒细胞（PMNL）分离制备方法下观察异丙酚对PMNL呼吸爆发活性的作用,以探讨不同PMNL制备方法对其呼吸爆发作用测量的影响。方法 将治疗剂量和10倍治疗剂量的异丙酚（6μg·mL-1,60μg·mL-1）与PMNL进行孵育,分别以大肠杆菌（E.coli）,12-肉豆蔻酰-13-乙酰佛波酸（PMA）或N-甲酞甲硫酰亮氨酚苯丙氨酸（FMLP）诱导产生呼吸爆发作用。所有标本均分为两份,分别经Ficoll分离法制备后使用,或以全血法直接测定。以流式细胞仪测定发生呼吸爆发作用而产生过氧化物的PMNL百分数。结果 在Ficoll分离组中,与对照组比较,6μg·mL-1和60μg·mL-1异丙酚显著抑制FMLP诱导的PMNL呼吸爆发作用（P<0.01）,60μg·mL-1异丙酚显著抑制PMA诱导的PMNL呼吸爆发作用（P<0.01）;全血法组中60μg·mL-1异丙酚对FMLP和 E.coli诱导的 PMNL呼吸爆发活性有显著抑制作用（P<0.05）。采用Ficoll法与全血法制备的PMNL比较,测定的异丙酚对呼吸爆发（以PMA和FMLP诱导）的抑制作用存在显著性差异（P<0.01）。结论 治疗剂量和10倍治疗剂量的异丙酚对于中性粒细胞的呼吸爆发活性有抑制作用,以流式细胞仪法测定PMN的呼吸爆发作用与PMN的分离制备方法有关。     

肠缺血/再灌注损伤时中性粒细胞呼吸爆发活性的变化

目的:研究肠缺血/再灌注(I/R)时中性粒细胞(PMN)呼吸爆发活性的变化.方法:30只成年雄性Wistar大鼠,按照随机数字表法分为假手术,缺血45 min,缺血45 min再灌注60min、120min、360min等5组.阻断肠系膜上动脉血流45min后复流,复制I/R模型:假手术组只进行同样的手术操作但不阻断肠系膜上动脉血流.在各时间点分别取门静脉血测定白细胞计数,并分离PMN进行化学发光(CL)测定.结果:肠I/R损伤过程中,缺血组与假手术组比较,PMN的CL峰值无明显差异(P＞0.05),再灌注组PMN的CL峰值均明显升高(P＜0.01).肠缺血组白细胞数量较假手术组降低,再灌注后开始回升,再灌注360 min时白细胞计数最高.PMN化学发光峰值变化和血白细胞计数的变化趋势呈显著正相关(r=0.748,P＜0.05).结论:肠I/R损伤可激活循环中的PMN,使血中的PMN数量增加,PMN的呼吸爆发化学发光活性明显升高,可能是引起全身炎症反应和器官损害的因素之一.     

体外循环术中持续吸入一氧化氮对人体多核粒细胞计数和呼吸爆发功能的影响

多核粒细胞(PMN)是人体重要的免疫杀伤细胞,参与人体特异性和非特异性炎症反应,体外循环术中的PMN激活可累及多脏器功能,是引起术后并发症、增加术后死亡率的重要因素之一。有效地调节PMN的功能对减少机体损伤有重要意义[1,2]。本研究拟在了解体外循环心脏手术中持续应用一氧化氮(NO)对病人全血PMN计数和呼吸爆发功能的影响。     

瑞芬太尼和异丙酚对健康志愿者体外静脉血中性粒细胞呼吸爆发的影响

目的 评价瑞芬太尼和异丙酚对健康志愿者体外静脉血中性粒细胞(PMNs)呼吸爆发的影响.方法 健康志愿者12名,年龄20～40岁,体重55～65kg,取肘静脉血5 ml抗凝.采用正交实验设计确立实验因素为瑞芬太尼和异丙酚;实验水平数为5水平,即瑞芬太尼空白对照、溶媒(甘氨酸)对照、瑞芬太尼5、50、500 ng/ml和异丙酚空白对照、溶媒(脂肪乳)对照、异丙酚5、50、500μg/ml,用正交表L25(56),观察药物对静息状态和脂多糖(LPS)激活状态下PMNs呼吸爆发的影响,静息状态的PMNs不用LPS进行刺激,按实验设计方案加入相应药物孵育3 h;激活状态的PMNs根据用药时机分为预防性用药和治疗性用药,预防性用药加入相应药物孵育1 h,再加入LPS(终浓度1μg/ml)孵育2 h;治疗性用药首先加入LPS(终浓度1 μg/ml)孵育1 h,再加入相应药物孵育2 h.结果 瑞芬太尼50 ng/ml可增强静息状态下PMNs的呼吸爆发;各剂量瑞芬太尼治疗性用药均可增强LPS激活状态下PMNs的呼吸爆发(P＜0.05),预防性用药对PMNs的呼吸爆发无影响(P＞0.05).各剂量异丙酚及脂肪乳可降低静息和LPS激活状态下PMNs的呼吸爆发(P＜0.05),但各剂量异丙酚与脂肪乳比较差异无统计学意义(P＞0.05).瑞芬太尼和异丙酚对静息状态下和激活状态下PMNs呼吸爆发的影响没有交互作用.结论 瑞芬太尼对PMNs呼吸爆发的影响可能与PMNs所处的状态、用药剂量及用药时机有关;异丙酚的溶媒可抑制PMNs的呼吸爆发,而异丙酚本身无作用,且这种抑制作用与PMNs所处的状态及用药时机无关;瑞芬太尼和异丙酚对PMNs呼吸爆发的影响没有交互作用.     

中性粒细胞在成人呼吸窘迫综合征中的作用

中性粒细胞介导的肺损伤是一多相性反应，趋化作用、休克期低肺血流量导致中性粒细胞在肺毛细血管中的积聚、特殊粘附－介导的中性粒细胞截留等都参与了中性粒细胞介导的象ＡＲＤＳ样的肺细胞损害。     

利多卡因对中性粒细胞致体外培养内皮细胞损伤的保护作用

目的 探讨利多卡因（Ｌｉｄｏ）对内毒素（ＥＴ）激活的中性粒细胞（ＰＭＮ）致内皮细胞损伤的保护作用。方法 利用体外培养的内皮细胞,建立ＥＴ－ＰＭＮ－血清（ＨＳ）致内皮细胞损伤的模型,选用原代培养的小牛主动脉内皮细胞,纯化后４－９代的细胞制成悬液,接种于培养板,随机分为三组：对照组（ＥＣ＋ＰＭＮ＋ＰＢＳ）,损伤组（ＥＣ＋ＰＭＮ＋ＨＳ＋１０μｇ／ｍｌＥＴ）和Ｌｉｄｏ组（ＥＣ＋ＰＭＮ＋ＨＳ＋１０μｇ／ｍｌ     

Hemodialysis with Cellulose Membranes Primes the Neutrophil Oxidative Burst

Abstract: Hemodialysis with cellulose membranes causes a complement-mediated neutropenia. Changes in neutrophil function have also been reported; however, it is unclear if these changes indicate a direct effect of the membrane on neutrophils or if they are a consequence of the neutropenia. We tested the hypothesis that neutrophil oxidative burst activity is enhanced during dialysis with cellulose membranes. Resting and Staphylococcus aureus -stimulated H₂O₂ production were determined predialysis and in blood entering and leaving the dialyzer during the first 30 min of dialysis and in blood leaving the membrane module in a single-pass on-line model of hemodialysis. Resting H₂O₂ production increased slightly but significantly during the first 30 min of dialysis. Transit of neutrophils through the dialyzer caused a marked increase in stimulated H₂O₂ production, indicating priming of the oxidative burst. However, priming was limited to the first 5 min of dialysis before the onset of neutropenia. In contrast, stimulation and priming of H₂O₂ production persisted throughout 30 min of single-pass on-line perfusion. These results indicate that cellulose membranes both stimulate and prime neutrophil oxidative burst activity but that these effects are partially obscured by neutropenia.     

Inhibition of Neutrophil Activation by Volatile Anesthetics Decreases Adhesion to Cultured Human Endothelial Cells

Background: Polymorphonuclear leukocytes (neutrophils, PMNs) have been shown to mediate vascular and tissue injury, leading to so-called systemic inflammatory response syndrome. The authors evaluated the effect of volatile anesthetics on neutrophil adhesion to human endothelial cells, focusing on whether the inhibitory effect observed is linked to an alteration in the function of endothelial cells or neutrophils.

Methods: The adhesion of human PMNs was quantified using cultured human umbilical vein endothelial cells (HUVECs). The increase in the number of adhering PMNs was assessed when HUVECs (with 1 mM hydrogen peroxide), PMNs (with 10 nM N-formyl-methionyl-leucyl-phenylalanine), or both were pre-stimulated. To determine the influence of volatile anesthetics on the adhesion of PMNs, the experiments were performed in the absence or presence of 0.5, 1, and 2 minimum alveolar concentration halothane, isoflurane, or sevoflurane, whereby HUVECs, PMNs, or both were pretreated with gas.

Results: Activation of HUVECs with hydrogen peroxide or stimulation of PMNs with N-formyl-methionyl-leucyl-phenylalanine resulted in a 2.5-fold increase in PMN adhesion. Preincubation of PMNs, separately, with halothane, isoflurane, or sevoflurane, respectively, abolished enhanced neutrophil adhesion to hydrogen peroxide-activated HUVECs and adhesion of PMNs prestimulated with N-formyl-methionyl-leucyl-phenylalanine to unstimulated HUVECs (maximal effect at 1 minimum alveolar concentration). No decrease in adhesion was detected when only HUVECs were pretreated with volatile anesthetics. Additional exposure of HUVECs and PMNs to volatile anesthetics had no inhibitory effect on adhesion greater than that seen when only PMNs were treated. Appropriately, the volatile anesthetics abolished the upward regulation of the adhesion molecule CD11b on PMNs (as evaluated at 1 minimum alveolar concentration each), whereas 1 minimum alveolar concentration halothane failed to affect the expression of P-selectin, an adhesion molecule on endothelial cells.     

吸入麻醉药的神经保护效应及可能机制

围术期的脑缺血风险极有可能留下致命性的损伤,而自19世纪60年代人们就发现吸入麻醉药具有神经保护的潜在特质,本文主要璧点综述过去30年在临床广泛使用的以七氟烷为代表的氟烷类吸入麻醉药．他们的保护作用及可能的机制,虽然陷于操作性和安全性等因素．绝大部分的研究数据基于动物模型的体外或体内实验．但是数据依然提示吸入麻醉药对于轻中度缺血损伤具有保护价值。     

吸入麻醉剂对人精子运动功能影响的体外研究

目的:观察吸入麻醉剂在体外对人精子运动功能的影响。方法:选择人精液20份,上游法优化处理后随机分为异氟醚实验组和七氟醚实验组,各10份。分别观测低浓度和高浓度异氟醚及七氟醚对精子活力的影响,并观察异氟醚和七氟醚停用1h后精子运动功能的变化。精子运动功能采用计算机辅助精子分析系统分析。结果:1.4%～5.6%异氟醚作用于精子0.5～4h后,精子活动率及活力显著升高。停用异氟醚后精子活动率及活力恢复至对照组水平。5.6%～42%异氟醚不引起精子活动率和活力的变化。42%～84%异氟醚可引起精子活动率和活力呈剂量依赖性下降。1.3%～84.5%七氟醚对精子活力无影响。结论:临床浓度异氟醚在体外作用于人精子,可以显著升高精子活动率和活力,并且作用可逆,随着浓度超过42%以上,精子活力和活动率逐渐下降。七氟醚对精子活力没有显著影响。     

Effects of Intravenous Anesthetics on Renal Ischemia/Reperfusion Injury

Background. Renal ischemia/reperfusion (I/R)-induced tubular epithelial cell injury, called ischemic acute renal failure, is associated with high mortality in humans. Protecting the kidney against I/R injury is very important during complicated renal operations, transplantation surgery, and anesthesia. Aim. The purpose of this study was to investigate and compare the efficiency of ketamine, thiopental, propofol, etomidate, and intralipid in reducing the injury induced by free radicals in a rat model of renal I/R. Method. Forty-two Wistar rats were divided into seven groups in our study. Rats in the sham group underwent laparotomy and waited for 120 minutes (min) without ischemia. Rats in the control group were given nothing with ischemia-reperfusion. Rats in the I/R groups were given ketamine (20 mg/kg), thiopental (20 mg/kg) propofol (25 mg/kg), etomidate (10 mg/kg) and 10% intralipid (250 mg/kg) intraperitoneally 15 min prior to the ischemia for 60 min, followed by reperfusion for 60 min. The blood samples and kidney tissues of the rats were obtained under anesthesia at the end of the reperfusion period. Biochemical malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), blood urea nitrogen (BUN), creatine (Cr), aspartate aminotransferase (AST) were determined, and histopathological analysis was performed with these samples. Results. MDA level was increased significantly in the control group (p < 0.05). Histopathological findings of the control group confirmed that there was renal impairment by tubular cell swelling, interstitial edema, medullary congestion, and tubular dilatation. MDA levels were lower in the ketamine, thiopental, and propofol groups compared to the control group (p < 0.05). In the thiopental and propofol groups, the levels of histopathological scores were significantly lower than control and etomidate groups in ischemia-reperfusion. Conclusion. Our results demonstrated that I/R injury was significantly reduced in the presence of propofol and thiopental. The protective effects of these drugs may belong to their antioxidant properties. These results may indicate that propofol and thiopental anesthesia protects against functional, biochemical, and morphological damage better than control in renal I/R injury.     

注射挥发性麻醉药对动物的效应

研究了注射挥发性麻醉药对动物的效应，在小鼠，乙醚的催眠ＥＤ５０是５．３５（ｓｃ）和１．６２（ｉｐ）ｍｌ／ｋｇ；ＬＤ５０是１３．７（ｓｃ）和２．３２（ｉｐ）ｍｌ／ｋｇ。甲氧氟烷的ＥＤ５０为０．７５（ｉｐ）和４．１２（ｉｍ）ｍｌ／ｋｇ；ＬＤ５０为１．２３（ｉｐ）５．８１（ｉｍ）ｍｌ／ｋｇ，ｉｐ氟烷的ＥＤ５０和ＬＤ５０分别是１．２０和１．９４ｍｌ／ｋｇ，ｉｐ安氟醚的ＥＤ５０和ＬＤ５０分别是３．０１和７．     

Behavioral Effects of Volatile Anesthetics in Caenorhabditis elegans

Background: The nematode Caenorhabditis elegans offers many advantages as a model organism for studying volatile anesthetic action: It has a simple, well-understood nervous system; it allows the researcher to do forward genetics; and its genome will soon be completely sequenced. C. elegans is immobilized by volatile anesthetics only at high concentrations and with an unusually slow time course. Here other behavioral dysfunctions are considered as anesthetic endpoints in C. elegans.

Methods: The potency of halothane for disrupting eight different behaviors was determined by logistic regression of concentration and response data. Other volatile anesthetics were also tested for some behaviors. Established protocols were used for behavioral endpoints that, except for pharyngeal pumping, were set as complete disruption of the behavior. Time courses were measured for rapid behaviors. Recovery from exposure to 1 or 4 vol% halothane was determined for mating, chemotaxis, and gross movement. All experiments were performed at 20 to 22 degrees Celsius.

Results: The median effective concentration values for halothane inhibition of mating (0.30 vol% - 0.21 mM), chemotaxis (0.34 vol% - 0.24 mM), and coordinated movement (0.32 vol% - 0.23 mM) were similar to the human minimum alveolar concentration (MAC; 0.21 mM). In contrast, halothane produced immobility with a median effective concentration of 3.65 vol% (2.6 mM). Other behaviors had intermediate sensitivities. Halothane's effects reached steady-state in 10 min for all behaviors tested except immobility, which required 2 h. Recovery was complete after exposure to 1 vol% halothane but was significantly reduced after exposure to immobilizing concentrations.