右美托咪啶对异氟醚抑制切皮时患者体动反应的肺泡气最低有效浓度的影响

目的 探讨右美托咪啶对异氟醚抑制切皮时患者体动反应的肺泡气最低有效浓度(MAC)的影响.方法 择期全身麻醉下行上腹部手术患者,年龄40～60岁,ASA分级Ⅰ或Ⅱ级,体重指数22～27 kg/m2,采用随机数字表法,将患者随机分为3组:对照组(C组)、小剂量右美托咪啶组(D1组)和大剂量右美托咪啶组(D2组).麻醉诱导前静脉输注右美托咪啶(生理盐水稀释至15 ml)0.4 μg/kg(D1组)、0.8μg/kg(D2组)及生理盐水15 ml(C组),15 min内输注完毕.静脉注射芬太尼-异丙酚-琥珀酰胆碱麻醉诱导,气管插管后机械通气并开启异氟醚挥发罐.采用序贯法确定麻醉维持期间异氟醚的呼气末浓度,C组、D1组和D2组第1例患者异氟醚呼气末浓度分别设定为1.0%、0.8%和0.6%,当异氟醚呼气末浓度达到预设水平并维持15 min以上,且肌颤搐恢复到对照值90%以上时开始手术,相邻浓度差值为0.2%.于切皮时评估患者体动反应,以各交叉点异氟醚呼气末浓度的均数为MAC,并计算95%可信区间(CI).结果 C组、D1组和D2组入选病例分别为15、17和16例.异氟醚抑制切皮时体动反应的MAC及其95%CI分别为:C组(1.03±0.23)%(95%CI 0.83%～1.21%)、D1组(0.72±0.19)%(95%CI 0.58%～0.85%)、D2组(0.51±0.27)%(95%CI 0.30%～0.71%).与C组比较,D1组和D2组MAC降低(P＜0.01),D2组MAC明显低于D1组(P＜0.05).结论 右美托咪啶可明显降低异氟醚抑制切皮时患者体动反应的MAC,且与剂量有关.

Abstract：

Objective To investigate the effect of dexmedetomidine on minimum alveolar concentration (MAC) of isoflurane required to inhibit the body movement during skin incision. Methods Forty-eight ASA Ⅰ or Ⅱ patients aged 40-60 yr with body mass index of 22-27 kg/m2 undergoing elective upper abdominal surgery under general anesthesia were randomly divided into 3 groups: control group (group C, n = 15);low dose dexmedetomidine group (group D1, n = 17) and high dose dexmedetomidine group (group D2, n = 16). The patients were unpremedicated. Dexmedetomidine 0.4 and 0.8 μg/kg in normal saline (NS) 15 ml was infused over 15 min before induction of anesthesia in D1 and D2 groups respectively. Anesthesia was induced with fentanyl-propofol-succinylcholine. The patients were mechanically ventilated after tracheal intubation. Anesthesia was maintained with isoflurane. MAC of isoflurane was determined by up-and-down technique. The initial end-tidal isofiurane concentration was set at 1.0%, 0.8% and 0.6% in C, D1 and D2 groups respectively. Each time the end-tidal isoflurane concentration was increased/decreased by 0.2%. Skin incision was made after 15 min of equilibration, when the twitch height returned to more than 90% of its control value. Movement of body and limbs including swallowing and coughing were carefully looked for when skin incision was made. MAC of isoflurane was the mean of end-tidal concentration of isoflurane of each crossover pair, and 95 % CI was calculated. Results MAC of isoflurane was significantly decreased in D1 and D2 groups as compared with group C and in group D2 as compared with group D1( P ＜ 0.05 or 0.01 ). Conclusion Dexmedetomidine can significantly decrease MAC of isoflurane required to inhibit the body movement during skin incision in a dose-dependent manner.     

不同剂量右美托咪啶对下腹部手术患者七氟醚MACBAR的影响

目的 评价不同剂量右美托咪啶对七氟醚抑制50%下腹部手术患者切皮诱发应激反应的最低肺泡气有效浓度(MACBAR)的影响.方法 择期全麻下拟行下腹部手术患者60例,年龄25～55岁,体重45～75 kg,ASA分级Ⅰ或Ⅱ级,采用随机数字表法,将患者随机分为对照组(D0组,n=15)和不同剂量右美托咪啶组(D1～3组,n=15).D0组不使用右美托咪啶,D1-3组经10 min静脉注射右美托咪啶0.1 μg/kg负荷剂量后,分别以0.4、0.8、1.2μg·kg-1·h-1的速率静脉输注30 min后进行麻醉诱导.D0-3组第1例患者呼气末七氟醚浓度分别为3.0%、2.5%、2.0%、1.5%,以切皮时患者MAP或HR较基础值上升＜15%为抑制交感肾上腺反应有效,若抑制交感肾上腺反应有效则下一例呼气末七氟醚浓度降低一级,若无效则升高一级,相邻浓度比为0.9.计算七氟醚MACBAR及其95%可信区间(95%CI).结果 D0～3组七氟醚MACBAR及其95%CI分别为:2.85%(2.44%～3.32%)、1.9l%(1.6l%～2.26%)、1.52%(1.3l%～1.77%)、1.34%(1.15%～1.57%).与D0组比较,D1-3组七氟醚MACBAR均降低(P＜0.05);与D1组比较,D2组和D3组七氟醚MACBAR降低(P＜0.05);D2组和D3组七氟醚MACBAR比较差异无统计学意义(P＞0.05).结论 右美托咪啶0.4、0.8和1.2μg·kg-1·h-1连续输注30 min可降低七氟醚MACBAR,增强七氟醚抑制应激反应的效应,且呈剂量依赖性.

Abstract：

Objective To investigate the effects of different doses of dexmedetomidine on the minimum alveolar concentration of sevoflurane for blunting responses to skin incision ( MACBAR ) in patients undergoing lower abdominal surgery. Methods Sixty ASA Ⅰ or Ⅱ patients, aged 25-55 yr, weighing 45-75 kg, undergoing electire lower abdominal surgery under general anesthesia, were randomly divided into 4 groups ( n = 15 each): control group (Do group) and 3 dexmedetomidine groups (D1, D2 and D3 groups). The patients were unpremedicated.Dexmedetomidine was not used in group D0. A loading dose of dexmedetomidine 0.1μg/kg was injected iv over 10 min, and then dexmedetomidine was infused at a rate of 0.4, 0.8 and 1.2 μg· kg- 1 · h - 1 for 30 min in groups D1-3 respectively. Anesthesia was induced with inhalation of 8 % sevoflurane. Laryngeal mask airway was inserted when BIS value decreased to 45-55. The patients were mechanically ventilated with inhalation of sevoflurane and a mixture of 50% nitrous oxide and 50% oxygen, and the fresh gas flow was set at 1 L/min. In D0-3 groups, the initial end-tidal concentrations of sevoflurane were 3.0%, 2.5%, 2.0% and 1.5% respectively. The patients' response to skin incision was described as effective if MR or MAP increased by ＜ 15%, or ineffective (MR or MAP increased by ≥ 15%). When the response was effective, the end-tidal concentration of sevoflurane was decreased in the next patient, when ineffective, increased, and the ratio between the two successive concentrations was 0.9.The MRCBAR of sevoflurane was determined by up-and-down method, and 95% confidence interval was calculated.Results The MRCBAR (95% confidence interval) of sevoflurane was 2.85% (2.44%-3.32%), 1.91%(1.61%-2.26%), 1.52% (1.31%-1.77%), and 1.34% (1.15%-1.57%)in D0-3 groups respectively. The MRCBAR of sevoflurane was significantly lower in D1-3 groups than in D0 group, and in D2 and D3 groups than in group D1 (P ＜0.05＝. There was no significant difference in MRCBAR of sevoflurane between D2 and D3 groups (P ＞0.05) .Conclusion Continuous infusion of dexmedetomidine at 0.4, 0.8 and 1.2 μg·kg-1 ·h-1 for 30 min results in a decrease in MACBAR of sevoflurane and enhances the inhibitory effect of sevoflurane on the stress response, and in a dose-dependent manner.     

右美托咪啶对七氟醚麻醉患儿麻醉恢复期躁动的影响

目的 评价右美托咪啶对七氟醚麻醉患儿麻醉恢复期躁动的影响.方法 择期全麻下行耳鼻喉科手术患儿300例,ASA分级Ⅰ或Ⅱ级,性别不限,年龄4～7岁,体重16～30 kg,采用随机数字表法,将其随机分为2组(n=150):对照组(C组)和右美托咪啶组(D组).D组麻醉诱导前经10min静脉输注0.5μg/kg右美托咪啶20 ml,C组输注生理盐水20 ml.给药结束后5 min时吸入8%七氟醚麻醉诱导,气管插管后行机械通气.吸人2%～ 3%七氟醚维持麻醉,术中维持BIS值40～60.记录麻醉恢复时间和术后2 h内躁动的发生情况.结果 与C组比较,D组麻醉恢复时间差异无统计学意义(P>0.05),躁动发生率降低(P<0.05).结论 右美托咪啶可降低七氟醚麻醉患儿麻醉恢复期躁动的发生.

Abstract：

Objective To investigate the effect of dexmedetomidine on agitation during recovery from sevoflurane anesthesia in children. Methods Three hundred ASA Ⅰ or Ⅱ children, aged 4-7 yr, weighing 16-30kg, scheduled for elective ear-nose-throat operation under general anesthesia, were randomly divided into 2 groups ( n = 150 each) : control group (group C) and dexmedetomidine group (group D) . Dexmedetomidine 0.5 μg/kg in 20 ml was infused intravenously over 10 min before anesthesia induction in group D, while equal volume of normal Saline was infused in group C. Anesthesia was induced with inhalation of 8 % sevoflurane 5 min after the end of administration . The children were tracheal incubated and mechanically ventilated. Anesthesia was maintained with inhalation of 2 % -3 % sevoflurane. BIS was maintained at 40-60 during operation. The recovery time and agitation within 2 h after operation were recorded. Results There was no significant difference in the recovery time between the two groups ( P > 0.05) . The incidence of agitation was significantly lower in group D than in group C ( P <0.05 ) . Conclusion Dexmedetomidine can reduce the occurrence of agitation during recovery from sevoflurane anesthesia in children.     

右美托咪啶对七氟醚麻醉患儿麻醉恢复期躁动的影响

Objective To investigate the effect of dexmedetomidine on agitation during recovery from sevoflurane anesthesia in children. Methods Three hundred ASA Ⅰ or Ⅱ children, aged 4-7 yr, weighing 16-30kg, scheduled for elective ear-nose-throat operation under general anesthesia, were randomly divided into 2 groups ( n = 150 each) : control group (group C) and dexmedetomidine group (group D) . Dexmedetomidine 0.5 μg/kg in 20 ml was infused intravenously over 10 min before anesthesia induction in group D, while equal volume of normal Saline was infused in group C. Anesthesia was induced with inhalation of 8 % sevoflurane 5 min after the end of administration . The children were tracheal incubated and mechanically ventilated. Anesthesia was maintained with inhalation of 2 % -3 % sevoflurane. BIS was maintained at 40-60 during operation. The recovery time and agitation within 2 h after operation were recorded. Results There was no significant difference in the recovery time between the two groups ( P > 0.05) . The incidence of agitation was significantly lower in group D than in group C ( P <0.05 ) . Conclusion Dexmedetomidine can reduce the occurrence of agitation during recovery from sevoflurane anesthesia in children.     

右美托咪啶对七氟醚麻醉患儿麻醉恢复期躁动的影响

Objective To investigate the effect of dexmedetomidine on agitation during recovery from sevoflurane anesthesia in children. Methods Three hundred ASA Ⅰ or Ⅱ children, aged 4-7 yr, weighing 16-30kg, scheduled for elective ear-nose-throat operation under general anesthesia, were randomly divided into 2 groups ( n = 150 each) : control group (group C) and dexmedetomidine group (group D) . Dexmedetomidine 0.5 μg/kg in 20 ml was infused intravenously over 10 min before anesthesia induction in group D, while equal volume of normal Saline was infused in group C. Anesthesia was induced with inhalation of 8 % sevoflurane 5 min after the end of administration . The children were tracheal incubated and mechanically ventilated. Anesthesia was maintained with inhalation of 2 % -3 % sevoflurane. BIS was maintained at 40-60 during operation. The recovery time and agitation within 2 h after operation were recorded. Results There was no significant difference in the recovery time between the two groups ( P > 0.05) . The incidence of agitation was significantly lower in group D than in group C ( P <0.05 ) . Conclusion Dexmedetomidine can reduce the occurrence of agitation during recovery from sevoflurane anesthesia in children.     

右美托咪啶预防儿童七氟醚麻醉苏醒期躁动效果的观察

目的观察应用右美托咪啶预防儿童七氟醚麻醉苏醒期躁动的效果。方法将56例接受七氟醚麻醉手术的患儿随机分为2组,每组28例。观察组:麻醉诱导后静脉泵注右美托咪定注射液0.5μg/kg(稀释到15 m L),10~20 min注完后开始手术。对照组:麻醉诱导后手术开始前泵注15 m L生理盐水。比较2组患儿右美托咪啶或生理盐水注射前(T0)、注射5 min后(T1)、患儿苏醒睁眼时间点(T2)及拔管5 min后(T3)心率、血压变化和麻醉后的苏醒时间、躁动情况等。结果对照组T2和T3时点的NAP和HR较T0明显升高,差异有统计学意义(P0.05);与对照组比较,观察组T2和T3时间点MAP明显降低,同时T1、T2和T3时间点HR明显降低,差异均有统计学意义(P0.05)。观察组患儿苏醒期躁动发生率低于对照组,苏醒时间长于于对照组,2组比较差异具有统计学意义(P0.05)。结论麻醉诱导后手术开始前应用右美托咪啶,在儿童七氟醚麻醉时能较好维持血流动力学的平稳,降低苏醒期的躁动发生率。     

右美托咪啶对大鼠脓毒症转归的影响

目的 探讨右美托咪啶对大鼠脓毒症转归的影响.方法 健康雄性SD大鼠,周龄10～14周,体重260～390 g,采用盲肠结扎-穿孔法制备脓毒症模型.取模型制备成功的大鼠90只,随机分为3组(n=30):对照组(C组)、咪达唑仑组(M组)和右美托咪啶组(D组).术毕C组静脉输注生理盐水1 ml/h;M组静脉输注咪达唑仑0.6 mg·kg-1·h-1;D组静脉输注右美托咪啶5 μg·kg-1·h-1,各组均持续8 h.各组取10只大鼠,观察术后24 h内的生存情况;各组取10只大鼠,于术前、术后2、4、5 h时取颈动脉血样,采用ELISA法测定血浆肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)的浓度;各组取10只大鼠,于术后8 h时测定肾功能.处死进行细胞因子和肾功能测定结束后未死亡的大鼠,取脾脏组织,采用Western blot法测定caspsse-3和泛素的表达.结果 与C组比较,M组和D组血浆TNF-α浓度降低,Na+排泄分数降低,脾脏组织caspase-3表达下调,泛素表达上调(P<0-05),血浆IL-6浓度和肌酐清除率差异无统计学意义(P>0.05);与M组比较,D组血浆TNF-α浓度降低(P<0.05),血浆IL-6浓度、Na+排泄分数、肌酐清除率、脾脏组织caspase-3和泛素的表达差异无统计学意义(P>0.05).C组、M组和D组术后24 h内生存率分别为10%、80%和90%.M组和D组术后24 h内生存率高于C组(P<0.05).结论 右美托咪啶可提高脓毒症大鼠的生存机率.     

右美托咪啶对慢性神经病理性痛大鼠脊髓背角神经元凋亡的影响

目的 评价右美托咪啶对神经病理性痛大鼠脊髓背角神经元凋亡的影响.方法 健康成年雄性SD大鼠72只,体重180～220 g,采用随机数字表法,将其随机分为3组(n=24):假手术组(S组)、慢性神经病理性痛组(CNP组)和右美托咪啶组(D组).S组仅分离坐骨神经但不结扎,CNP组和D组采用结扎坐骨神经的方法制备大鼠神经病理性痛模型,D组于结扎坐骨神经结束开始至处死前,腹腔注射右美托咪啶50μg/kg,1次/d,S组和CNP组注射等容量生理盐水.于术前1d、术后3、7、14 d(T0-3)时测定大鼠机械缩足阈值(MWT)和热缩爪潜伏期(TWL);于T1-3时测定痛阈后每组随机处死8只大鼠,取L4,5脊髓组织,采用免疫组化法检测脊髓背角Bcl-2及caspase-3的表达水平,采用透射电镜观察脊髓背角浅层神经元超微结构.结果 与S组比较,CNP组和D组T1-3时MWT降低,TWL缩短,脊髓背角Bcl-2和caspase-3表达上调(P＜0.05);与CNP组比较,D组T1 -3时MWT升高,TWL延长,脊髓背角Bcl-2表达上调,caspase-3表达下调(P＜0.05).脊髓背角浅层神经元超微结构:S组基本正常,CNP组细胞凋亡数目增加,D组细胞凋亡数目较CNP组减少.结论 腹腔注射右美托咪啶可减轻大鼠慢性神经病理性痛,其机制可能与抑制脊髓背角神经元凋亡有关.     

不同剂量右美托咪啶对腹腔镜卵巢囊肿剥除术患者七氟醚用量的影响

目的 评价不同剂量右美托咪啶对腹腔镜卵巢囊肿剥除术患者七氟醚用量的影响.方法 择期全麻下行腹腔镜卵巢囊肿剥除术患者80例,ASA分级Ⅰ或Ⅱ级,年龄25～50岁,体重指数18～ 25 kg/m2,采用随机数字表法,将患者随机分为4组(n=20):对照组(C组)于切皮前10 min静脉输注生理盐水20 ml;低、中和高剂量右美托咪啶组(DL组、DM组和DH组)于切皮前10 min分别静脉输注右美托咪啶0.3、0.6、0.9 μg/kg,输注时间10 min.吸入七氟醚维持麻醉,术中维持Narcotrend值40～50.于给予右美托咪啶前即刻(T1)、切皮(T2)、气腹即刻(T3)、气腹后10 min(T4)和术毕(T5)时测定呼气末七氟醚浓度(ETsev),记录单位时间七氟醚用量、苏醒时间和拔除气管导管时间,拔除气管导管后10 min观察躁动发生情况,于入室静卧10 min(T0)、T3～5时采集外周静脉血样,用快速血糖分析仪测定血糖,用放射免疫法测定血清皮质醇浓度.结果 C组、DL组、DM组和DH组单位时间七氟醚用量、T2～5时ETsev、T3～5时血糖和皮质醇浓度依次降低(P＜0.05);与C组比较,DL组、DM组和DH组拔除气管导管时间、苏醒时间缩短,躁动发生率降低(P＜0.05).结论 右美托咪啶可呈剂量依赖性地减少腹腔镜卵巢囊肿剥除术患者七氟醚用量.     

右美托咪啶的药理作用及临床应用进展

右美托咪啶为高效、高选择性的α2肾上腺素能受体激动剂，具有剂量依赖性的镇静、镇痛、抗焦虑、交感神经抑制等作用，副作用少而轻，已于1999年在美国批准用于重症监护病房（icu）成人的镇静、镇痛，并已在神经外科手术，用于术前用药、全麻辅助药、术后镇痛，治疗撤药反应等诸多临床实践中获得成功应用。现就其药理作用及临床应用作一综述。     

右美托咪定对丙泊酚诱导新生大鼠大脑发育的远期影响

目的探讨右美托咪定对丙泊酚诱导新生大鼠大脑发育的远期影响。方法 SD大鼠35只,雌雄不拘,7日龄,体重10~15 g,采用随机数字表法随机分为七组:生理盐水组(N组)、脂肪乳剂组(F组)、丙泊酚100 mg/kg组(P组)、右美托咪定75μg/kg组(D组)、右美托咪定25μg/kg+丙泊酚100 mg/kg组(PD25组)、右美托咪定50μg/kg+丙泊酚100 mg/kg组(PD50组)、右美托咪定75μg/kg+丙泊酚100 mg/kg组(PD75组),每组5只。各组新生大鼠按相应给药方案处理。待大鼠苏醒后放回笼中继续饲养至9周时,采用Morris水迷宫实验测定大鼠空间学习记忆能力;水迷宫实验结束后,断头取脑,制作脑组织切片,采用TUNEL法检测海马神经细胞凋亡情况,免疫组织化学法检测海马突触后致密蛋白95(PSD95)含量。结果与N组比较,P组、PD25组和PD50组逃避潜伏期明显延长,穿越原平台位置次数明显减少,海马神经细胞凋亡率明显升高,海马PSD95含量明显降低(P0.05)。与P组比较,PD50组、PD75组逃避潜伏期明显缩短,穿越原平台位置次数明显增加,海马神经细胞凋亡率明显降低(P0.05);PD75组海马PSD95含量明显升高(P0.05)。与PD25组比较,PD50组和PD75组逃避潜伏期明显缩短,穿越原平台位置次数明显增加,海马神经细胞凋亡率明显降低(P0.05);PD75组海马PSD95含量明显升高(P0.05)。与PD50组比较,PD75组海马神经细胞凋亡率明显降低,海马PSD95含量明显升高(P0.05)。结论应用右美托咪定50、75μg/kg预处理可以减轻丙泊酚诱导致新生大鼠成年后认知功能障碍,部分机制可能是通过减轻海马神经细胞凋亡和上调PSD95基因的表达;未见右美托咪定对发育期大脑有神经毒性。     

异氟醚通过上调NMDA受体导致发育期大鼠海马神经元凋亡

目的探讨异氟醚麻醉对新生大鼠海马神经元N-甲基-D-天冬氨酸(NMDA)受体亚基及凋亡的影响。方法新生1d的SD大鼠36只,雌雄不拘,取海马组织进行原代培养。采用随机数字表法将培养海马神经元5d的培养皿随机分为三组:对照组(C组)、异氟醚组(I组)和AP5+异氟醚组(A组),每组12只。I组和A组培养的海马神经元放置在密闭箱中,吸入1.5%异氟醚和纯氧,吸入时间6h,C组不做任何处理。于异氟醚麻醉结束后2、4、6、24h(C组于相应时点),提取海马神经元总mRNA和总蛋白,采用RT-PCR法测定NR2A mRNA、NR2BmRNA和caspase-3mRNA的表达量,采用Westen blot法测定caspase-3蛋白含量。结果与C组比较,异氟醚麻醉结束后2、4和6hI组海马神经元NR2AmRNA和NR2BmRNA的表达量明显上调(P0.05)。与C组和A组比较,I组异氟醚麻醉结束后2、4和6h海马神经元caspase-3mRNA的表达量、异氟醚麻醉后4和6h海马caspase-3蛋白含量明显升高(P0.05)。结论吸入1.5%异氟醚可能通过上调新生大鼠海马神经元NMDA受体导致发育神经元凋亡,阻断NMDA受体可以预防异氟醚导致的发育期海马神经元凋亡。     

右美托咪定对下腹部手术患者异氟醚呼气末有效浓度的影响

目的以脑电双频指数（BIS）为麻醉镇静深度指标,探讨右美托咪定（Dex）的不同输注速率对下腹部手术患者异氟醚呼气末有效浓度的影响。方法妇科剖腹手术患者60例,ASAⅠ或Ⅱ级,随机均分为:生理盐水对照组（C组）,Dex 0.4μg/kg组（D₁组）:Dex负荷量0.4μg/kg+维持量0.4μg·kg^-1·h^-1,Dex 0.8μg/kg组（D₂组）:Dex负荷量0.8μg/kg+维持量0.8μg·kg^-1·h^-1。三组负荷量药物均以微量泵于麻醉诱导前在10 min内泵注完毕。麻醉诱导:静注丙泊酚1～3mg/kg、芬太尼3μg/kg、维库溴铵0.12 mg/kg,当BIS<55时行气管插管。术中根据BIS值变化调节异氟醚吸入浓度维持BIS在40～55。术中持续监测血流动力学变化、异氟醚吸入和呼气末浓度。结果术中及术毕D₁、D₂组异氟醚呼气末浓度均明显低于C组（P<0.05或P<0.01）,且D₂组明显低于D₁组（P<0.05）。与C组比较,气管插管及拔管时D₁组及D₂组血流动力学更稳定。结论以BIS值为监测标准,Dex能有效降低异氟醚呼气末浓度,提高围术期血流动力学稳定性,未见严重不良反应。     

抗氧化剂MitoQ对异氟醚诱导大鼠海马神经元损伤的影响及机制

目的探讨抗氧化剂MitoQ对异氟醚诱导的新生大鼠海马神经元细胞损伤的影响及潜在机制。方法 SPF级健康SD大鼠15只,7日龄,体重15~20g。采用随机数字表法分为三组:对照组(C组)、异氟醚组(I组)和异氟醚+MitoQ组(IM组),每组5只。C组吸入空-氧混合气体。Ⅰ组于出生后7、14和21d吸入1.5%异氟醚2h,IM组在每次吸入异氟醚前腹腔注射MitoQ0.4ml/kg。于出生后28d采用HE染色观察各组大鼠海马CA1区海马神经元细胞形态。分离培养新生大鼠原代海马神经元细胞培养并分组处理,采用MTT法和TUNEL原位荧光染色法检测细胞存活率和凋亡率;采用硫代巴比妥酸法和黄嘌呤氧化酶法检测细胞中丙二醛(MDA)浓度和超氧化物歧化酶(SOD)活性;采用Rhodamine 123染色荧光显微镜照相法检测线粒体膜电位(MMP),DCFH-DA染色荧光显微镜照相法检测细胞内活性氧簇(ROS)生成量,采用Western blot法检测海马神经元细胞中Bax、Bcl-2和caspase-3蛋白含量。结果与C组比较,Ⅰ组大鼠海马组织神经细胞受损明显,细胞数目减少,Ⅰ组细胞存活率明显降低,细胞凋亡率明显升高,MDA浓度明显升高,SOD活性明显降低,ROS生成量明显增加,MMP水平明显降低,Bax和caspase-3蛋白含量明显升高,Bcl-2蛋白含量明显降低(P0.05);与Ⅰ组比较,IM组大鼠海马组织神经细胞损伤减少,细胞存活率明显升高,细胞凋亡率明显降低,MDA浓度明显降低,SOD活性明显升高,ROS生成量明显减少,MMP水平明显升高,Bax和caspase-3蛋白含量明显降低,Bcl-2蛋白含量明显升高(P0.05)。结论抗氧化剂MitoQ可明显抑制异氟醚诱导的海马神经元细胞损伤,这与其拮抗细胞氧化应激和维持线粒体功能作用密切相关。     

右美托咪定对脂多糖诱导脐静脉内皮细胞凋亡的影响

目的 评价右美托咪定对脂多糖(lipopolysaccharide,LPS)诱导的血管内皮细胞凋亡的影响.方法 参照随机数字表法将人脐静脉内皮细胞HUVEC-12随机分为4组(每组20孔):正常对照组(C组)、右美托咪定组(D组)、LPS组(L 组)、LPS+右美托咪定组(L+D组),培养24 h后:四甲基偶氮唑盐微量酶反应比色法(MTT法)和流式细胞术分别检测细胞活力和细胞凋亡率,黄嘌呤氧化酶法和硫代巴比妥酸法(thiobarbituric acid,TBA)测定各组细胞超氧化物歧化酶(superoxidedismutase,SOD)的活性和丙二醛(malonaldehyde,MDA)的含量,Western blot法检测细胞多聚腺苷酸二磷酸-1(Poly-ADP Ribosy polymerase-1,PARP-1)蛋白裂解片段的表达.结果 L组和L+D组细胞活力分别是0.95±0.08和1.08±0.10(P＜0.05),与C组比较,分别降低36％和27％;L组和L+D组细胞凋亡率分别是(14.7±1.8)％和(8.8±1.1)％(P＜0.05),分别是C组的2.6倍和1.1倍;L组和L+D组细胞SOD活性分别是(99±6) U/mg和(182±9) U/mg(P＜0.05),与C组比较,分别降低53％和14％;L组和L+D组细胞MDA含量分别是(29.9±1.8) nmol/mg和(19.3±2.1) nmol/mg(P＜0.05),分别是C组的1.6倍和79％;L组和L+D组细胞内PARP-1片段(相对分子质量89×103)表达分别是1.152±0.095和0.564±0.045 (P＜0.05),分别是C组的4.8倍和1.8倍;D组上述指标的差异无统计学意义(P＞0.05).结论 右美托咪定可有效减少LPS诱导下脐静脉内皮细胞的凋亡,其机制可能与抑制氧化应激、下调PARP-1裂解片段的表达有关.     

异氟醚对PC12细胞株细胞周期与凋亡的影响

目的 探讨异氟醚对PC12细胞株细胞周期与凋亡的影响.方法 经神经生长因子孵育7d的神经元样PC12细胞,培养于25 cm2培养瓶,采用随机数字表法,将其随机分为2组(n=6):对照组(C组)和异氟醚组(Ⅰ组).C组正常培养,Ⅰ组用1.2％异氟醚处理12 h.采用倒置相差光学显微镜观察细胞形态;收集细胞,采用流式细胞术测定细胞凋亡率、细胞周期、线粒体膜电位(MMP)及胞浆钙离子浓度([Ca2+]i).结果 与C组比较,Ⅰ组G0/G1期细胞比例减少,S期和G2/M期细胞比例增加,细胞凋亡率增加,MMP降低,[Ca2+];增加(P＜0.05).Ⅰ组细胞形态发生损伤变化.结论 1.2％异氟醚处理神经元样PC12细胞12 h,可异常启动细胞周期,致细胞发生凋亡.     

异氟醚麻醉对大鼠海马蛋白质组的影响

目的 研究异氟醚麻醉后大鼠海马蛋白质组的变化.方法 将10只8月龄SD大鼠随机均分为异氟醚组(I组)和对照组(C组).1组大鼠以1.2%异氟醚吸入麻醉2 h,C组吸氧对照.于麻醉处理或吸氧对照结束后24 h取海马组织行双向凝胶电泳和质谱分析以鉴定差异蛋白点.结果 双向凝胶电泳结果显示I和C组差异蛋白质点共有17(4/13)个,MAL DI-TOF-MS分析后鉴定出12种蛋白质.结论 异氟醚麻醉可以引起大鼠海马蛋白质组变化,这些蛋白质变化可能具有一定的神经元保护作用.     

二氮嗪预处理对缺氧复氧后大鼠海马神经元凋亡的影响

目的研究线粒体内膜ATP敏感性钾通道（Mito-KAw）特异性开放剂二氮嗪预处理对缺氧复氧后大鼠海马神经元凋亡的影响。方法取离体培养的大鼠海马神经元，随机分为4组：对照组（A组）、二氮嗪30μmol／L组（B组）、二氮嗪1（30μmol／L组（C组）、二氮嗪100μmol／L＋Mito-KATP特异性阻断剂5．羟葵酸100μmol／L组（D组），各组神经元每天给予相应药物预处理1h，连续3d，继而缺氧4h复氧24h，观察神经元的活力、凋亡率、Bax和Bd．2蛋白的表达水平。结果与其它3组比较，C组海马神经元活力增强，凋亡率降低，Bcl．2蛋白表达水平升高，Bax蛋白表达水平下降（P〈0．01）。结论100μmol／L二氮嗪预处理通过改善Bcl-2与Bax蛋白表达的失衡，降低神经元的凋亡，对大鼠海马缺氧复氧神经元产生了保护效应。     

短暂性脑缺血对老年大鼠海马神经元凋亡的影响

目的 探讨短暂性脑缺血对老年大鼠海马神经元凋亡的影响。方法 健康老年雄性Wistar大鼠100只,按Pusinelli方法建立四动脉阻断法全脑缺血模型,随机分为4组（n=25）：脑缺血1min组（I1组）、脑缺血3min组（I3组）、脑缺血5min组（15组）和假手术组（C组）。每组均于再灌注12h、1d,2d、3d和7d各随机处死5只大鼠。随机取其中4只大鼠的海马组织制作石蜡切片,另1只大鼠断头处死后,冰上提取海马CAl区脑组织,制作电镜标本。透射电镜观察神经元超微结构,TUNEL法检测神经元凋亡,免疫组织化学法检测caspase．3的表达。结果 各组于光镜和电镜下均可见凋亡神经元。与C组、I1组相比,I3组、I5组凋亡细胞数和caspase-3表达阳性细胞数均增高（P〈0．05）;与I3组相比,I5组凋亡细胞数和caspase-3表达阳性细胞数均增高（P〈0．05）。结论 脑缺血3～5min对老年大鼠不产生预处理的效果,可引起脑神经元凋亡。