鞘内注射吗啡和可乐定对切口痛大鼠脊髓背角pCREB表达的影响

目的 观察鞘内注射吗啡和可乐定对切口痛大鼠脊髓背角磷酸化环腺苷酸反应原件结合蛋白(pCREB)表达的影响.方法 选择雄性SD大鼠80只,随机均分为五组:切口痛组(A组)、鞘内注射吗啡2.5μg组(B组)、鞘内注射可乐定5μg组(C组)、鞘内注射吗啡2.5μg+可乐定5μg组(D组)和假手术组(E组).观察大鼠术后2h机械缩足反射阈值(MWT)、热缩足潜伏期(TWL)和脊髓背角pCREB表达的变化.结果 与E组比较,A、B、C、D组MWT降低,TWL缩短,脊髓背角pCREB免疫反应阳性神经元数量和pCREB蛋白表达增加(P<0.01).与A组比较,D组MWT升高,TWL延长,脊髓背角pCREB免疫反应阳性神经元数量和pCREB蛋白表达减少(P<0.01).结论 鞘内注射吗啡加可乐定可抑制大鼠切口痛,这可能与其引起的脊髓背角pCREB的表达增加有关.     

鞘内注射吗啡对福尔马林炎性疼痛大鼠脊髓背角环氧化酶-2表达的影响

目的评价鞘内注射吗啡对福尔马林炎性疼痛大鼠脊髓背角环氧化酶-2（COX-2）表达的影响。方法32只鞘内置管成功的雄性SD大鼠，随机分为4组（n=8）：对照组（C组）、模型组（F组）、生理盐水组（NS组）及吗啡组（M组）。鞘内置管后5d，F组、NS组及M组大鼠于左后足掌部皮下注射5％福尔马林50μl，注射福尔马林前30min，NS组鞘内注射20μl生理盐水，M组鞘内注射10μl（10μg）吗啡和10出生理盐水，C组不给任何处理，采用疼痛加权评分评价疼痛行为学。F组、NS组及M组于注射福尔马林后24h，C组于鞘内置管后6d处死大鼠，取L5脊髓，采用免疫组织化学方法观察脊髓背角COX-2表达。结果吗啡可减轻福尔马林炎性疼痛；与C组比较，F组、NS组脊髓背角COX-2表达增加（P〈0．01）；与F组、NS组比较，M组脊髓背角COX-2表达降低（P〈0．01）。结论鞘内注射吗啡可抑制福尔马林炎性疼痛引起的脊髓中COX-2表达增加，可能与吗啡的抗伤害和镇痛作用有关．     

鞘内注射吗啡对切口疼痛大鼠脊髓背角蛋白激酶Cγ免疫反应的影响

目的 研究鞘内注射吗啡对切口疼痛大鼠脊髓背角蛋白激酶Cγ(PKCγ)免疫反应的影响。方法 SD雄性大鼠24只,随机分为4组(每组6只):假手术组(Ⅰ组)、对照组(Ⅱ组)术前30 min鞘内注射人工脑脊液20μl,术后吗啡治疗组(Ⅲ组)、术前吗啡治疗组(Ⅳ组)分别于术后和术前30min鞘内注射吗啡5μg(10 μl)。所有大鼠均按Brennan法制成切口疼痛模型,用免疫组织化学方法观察脊髓背角PKCγ的表达。结果 Ⅱ组术侧脊髓背角PKCγ-IR表达高于非术侧及Ⅰ组(P<0.01)。与Ⅱ组比较,Ⅲ组、Ⅳ组脊髓背角PKCγ-IR表达降低(P<0.05或0.01),而Ⅲ组、Ⅳ组比较差异无显著性。结论 在大鼠切口疼痛模型中,鞘内注射吗啡的镇痛作用可能与抑制脊髓背角的PKCγ-IR免疫反应有关。     

鞘内预注L-NAME对神经痛大鼠脊髓内c-fos基因表达的影响

目的 观察鞘内预先应用非选择性NOS抑制剂——L-NAME对结扎坐骨神经所致神经痛大鼠脊髓背角内c-fos基因表达的影响。方法 选择鞘内置管后无神经损伤症状的SD雌性大鼠84只,随机分为4组。A组:假手术组(n=16);B组:坐骨神经结扎组(n=24);C组:假手术前15min鞘内注射L-NAME 10μl(250μg)(n=16);D组:坐骨神经结扎前15min鞘内注射L-NAME 10μl(250μg)(n=24)。各组动物均再随机平均分为4个亚组,术后分别存活1d、3d、7d和14d。另有4只没有接受任何手术的大鼠处死后作为对照。用免疫组织化学方法观察各组大鼠同侧脊髓背角内c-fos基因的表达情况。结果 与对照组相比,在术后各测量时间点A、B两组大鼠同侧脊髓背角内c-fos基因的表达均明显增强,其中以B组最为明显(P<0.05)。鞘内预注L-NAME可明显抑制结扎坐骨神经所诱导的大鼠同侧脊髓背角内c-fos基因的表达,使D组大鼠同侧脊髓背角内Fos阳性细胞的数目在术后第3d、7d和14d分别较B组下降53.8％、57.1％和43.2％(P<0.05),但A组和C组大鼠同侧脊髓背角内Fos阳性细胞的数目没有差异。结论 一氧化氮是介导神经痛发生的一种重要介质,鞘内预先应用L-NAME可有效减少或预防神经痛的发生。     

鞘内注射DREAM-shRNA对神经病理性痛大鼠脊髓背角p-CREB表达的影响

目的 探讨鞘内注射转录因子下游调控元件拮抗因子-短发夹RNA(DREAM-shRNA)对神经病理性痛大鼠脊髓背角磷酸化环磷酸腺苷反应元件结合蛋白(p-CREB)表达的影响.方法 成年健康雄性SD大鼠,体重280～320 g,采用坐骨神经慢性压迫(CCI)法建立大鼠神经病理性痛模型.于CCI后第3天鞘内置管.取鞘内置管成功的大鼠24只,随机分为4组,每组6只,假手术组(S组):仅暴露坐骨神经,不结扎;神经病理性痛组(NP组):于CCI后第8天鞘内注射生理盐水10 μl;RNA干扰组(RNAi组):于CCI后第8天鞘内注射DREAM-shRNA 5 μl和牛理盐水5 μl;空白载体组(BV组):于CCI后第8天鞘内注射慢病毒空白载体5 μl和生理盐水5μl,各组连续注射7 d.于CCI前1 d(T0,基础状态)、CCI后第7～14天(T1-8)时测定机械痛阈.于CCI后第15天时测定脊髓背角绿色荧光蛋白(GFP)和p-CREB的表达水平.结果 与基础值比较,各组各时点机械痛阈降低(P<0.05或0.01);与T1时比较,NP组和BV组T5-8时机械痛阈降低,RNAi组T8时机械痛阈升高(P<0.05或0.01);与S组比较,NP组和BV组机械痛阈降低,RNAi组T2时机械痛阈降低,T8时升高,NP组、RNAi组和BV组脊髓背角p-CREB表达上调(P<0.05);与NP组比较,RNAi组T6-8时机械痛阈升高,脊髓背角p-CREB表达下调(P<0.05).RNAi组脊髓背角可见大量绿色荧光,即GFP表达阳性,其余3组脊髓背角未见绿色荧光,即GFP无表达.结论 鞘内注射DREAM-shRNA缓解大鼠神经病理性痛的机制可能与抑制脊髓背角p-CREB的表达有关.     

鞘内注射罗哌卡因对大鼠脊髓的神经毒性

目的 评价鞘内注射罗哌卡因对大鼠脊髓的神经毒性.方法 取鞘内置管成功的雄性SD大鼠60只,体重180～220 g,随机分为6组(n=10),分别鞘内注射0.75%布比卡因17 μl(A1组)、0.75%罗哌卡因20μl(A2组)、1%罗哌卡因15μl(A3组)、0.75%布比卡因34μl(B1组)、0.75%罗哌卡因40μl(B2组)和1%罗哌卡因30μl(B3组).注药后记录出现双后肢瘫痪时间和运动功能恢复情况.注药后6 h取腰膨大处脊髓,采用免疫组织化学法计数fos蛋白阳性细胞,测定fos蛋白表达;采用RT-PCR技术测定c-fos mRNA表达;透射电镜观察脊髓超微结构.结果 与A1组比较,A3组和B1组出现双后肢瘫痪时间缩短,B1组fos蛋白阳性细胞计数和fos蛋白表达升高(P<0.01);与A2组比较,A3组和B2组出现双后肢瘫痪时间缩短,B2组fos蛋白阳性细胞计数和fos蛋白表达升高(P<0.01);与A3组、B1组和B2组比较,B3组出现双后肢瘫痪时间缩短,双后肢运动功能恢复率降低,fos蛋白阳性细胞计数、fos蛋白表达和c-fos mRNA表达均升高(P<0.01),脊髓损伤加重.结论 鞘内注射0.75%罗哌卡因和小剂量1%罗哌卡因对大鼠无脊髓神经毒性;鞘内注射大剂量1%罗哌卡因对大鼠可产生脊髓神经毒性,但比大剂量0.75%布比卡因脊髓神经毒性小.     

鞘内注射布托啡诺混合氯胺酮对炎性痛大鼠脊髓背角cAMP-PKA-CREB信号转导通路的影响

目的 探讨鞘内注射布托啡诺混合氯胺酮对炎性痛大鼠脊髓背角环磷腺苷-蛋白激酶A-环磷腺苷反应元件结合蛋白(cAMP-PKA-CREB)信号转导通路的影响.方法 雄性SD大鼠,体重240～280 g,取鞘内置管成功的大鼠24只,随机分为4组(n=6):炎性痛组(IP组)、布托啡诺组(B组)、氯胺酮组(K组)和布托啡诺+氯胺酮组(BK组).置管后5 d,于大鼠左后足掌面皮下注射5%甲醛50μl,以制备炎性痛模型.IP组、B组、K组和BK组于皮下注射甲醛前30 min分别鞘内注射生理盐水10 μl、布托啡诺12.5 μg、氯胺酮50μg、布托啡诺12.5μg混合氯胺酮50μg.注射甲醛后1 h内,每5 min观察大鼠痛行为学,并计算痛加权评分(PIS评分);于注射甲醛后2 h时处死大鼠,取L5脊髓组织,采用免疫组化法测定脊髓背角PKA和磷酸化CREB(p-CREB)的表达水平,并行免疫组化染色分级.结果 大鼠注射甲醛后均表现出典型的痛双相期,即急性痛时相(第1时相)和继发性痛时相(第2时相).与IP组比较,BK组第1、2时相PIS评分降低,大鼠脊髓背角PKA、p-CREB表达下调,免疫组化染色分级降低(P<0.05或0.01),B组、K组上述指标差异无统计学意义(P>0.05).结论 鞘内注射布托啡诺混合氯胺酮可减轻大鼠炎性痛,其机制可能与抑制脊髓背角cAMP-PKA-CREB信号转导通路有关.     

鞘内注射吗啡加可乐定对切口痛大鼠脊髓背角蛋白激酶A催化亚单位表达的影响

目的 观察鞘内注射(intrathecal injection,IT)吗啡加可乐定对切口痛大鼠脊髓背角蛋白激酶A(protein kinaseA,PKA)催化亚单位表达的影响.方法 选择鞘内置管成功的雄性SD大鼠80只,随机分为5组,每组16只,分别为假手术组、对照组、吗啡2.5μg组、可乐定5 μg组和吗啡2.5 μg+可乐定5μg组.按Yaksh法鞘内置管,按Brennan法制作大鼠足底切口疼痛模型,用机械缩爪反射阈值(mechanical withdrawal threshold.MWT)和热缩爪潜伏期(thermal withdrawal latency,TWL)观察疼痛行为学变化,应用免疫组织化学法和免疫印迹法测定大鼠脊髓背角PKA催化亚单位表达的变化.结果 与假手术组比较,术后2h对照组大鼠的MWT明显降低,TWL明显缩短(P<0.01),脊髓背角PKA催化亚单位免疫反应阳性神经元数量和神经元胞浆内PKA催化亚单位表达明显增加(P<0.01);与对照组比较,吗啡2.5μg+可乐定5μg组大鼠的MWT明显增加,TWL明显延长(P<0.01),脊髓背角PKA催化亚单位免疫反应阳性神经元数量和神经元胞浆内PKA催化哑单位表达明显减少(P<0.01);而吗啡2.5μg组和可乐定5μg组大鼠的MWT、TWL、脊髓背角PKA催化亚单位免疫反应阳性神经元数量和神经元胞浆内PKA催化亚单位表达与对照组比较均无统计学意义.结论 在大鼠切口痛模型中,IT可乐定能增强吗啡的抗伤害作用,其机制可能与其抑制切口痛引起的脊髓背角PKA催化亚单位的表达增加有关.     

鞘内注射反义蛋白激酶Cγ寡核苷酸对慢性吗啡耐受大鼠痛觉过敏的影响

目的探讨鞘内注射反义蛋白激酶Cγ(PKCγ)寡核苷酸对慢性吗啡耐受大鼠痛觉过敏的影响。方法 24只雌性SD大鼠随机分为四组,每组6只,分别为正常组、耐受组、正义组和反义组。正常组不行任何处理;耐受组、正义组和反义组每日2次分别于鞘内注射40μg吗啡,连续5 d,建立吗啡耐受模型。此后每日继续给予吗啡,耐受组、正义组和反义组经鞘内分别注入20μl生理盐水、正义或反义的PKCγ寡核苷酸20μg,每日一次,连续6 d,断头处死大鼠,分离L2-6脊髓,RT-PCR方法检测脊髓PKCγ、PKCα的mRNA表达,Western blot法测定PKCγ、PKCα的蛋白表达。分别于置管前2 d、注射反义PKCγ寡核苷酸后2、4、5 d测定辐射热痛阈值。结果正常组、反义组注射反义PKCγ寡核苷酸后4、6 d痛阈值长于正义组(P<0．05)。四组脊髓背角PKCα mRNA及蛋白表达差异无统计学意义(P>0．05)。与耐受组比较,反义组脊髓背角PKCγ mRNA和蛋白表达降低(P<0．05)。正义组和反义组脊髓背角PKCγ蛋白表达低于耐受组,反义组脊髓背角PKCγ蛋白表达低于正义组(P<0．05)。结论反义PKCγ寡核苷酸通过下调脊髓背角PKCγ蛋白的表达,能够逆转吗啡耐受大鼠痛觉过敏。     

鞘内预注射L-NAME对神经性疼痛大鼠脊髓背角降钙素基因相关肽表达的影响

目的 观察鞘内预注射NG-硝基-L-精氨酸-甲基酯(L-NAME)对结扎坐骨神经所致神经性疼痛大鼠脊髓背角降钙素基因相关肽(CGRP)表达的影响。方法 选择鞘内置管后无神经损伤症状的SD雌性大鼠96只,随机分为4组,每组24只。A组:假手术组;B组:坐骨神经结扎组;C组:假手术前15 min鞘内注射L-NAME 10 μl(250 μg);D组:坐骨神经结扎前15 min鞘内注射L-NAME 10 μl(250 μg)。各组分别在术后第1、4、7和14天随机处死6只大鼠。采用免疫组织化学方法观察各组大鼠结扎侧脊髓背角CGRP的表达。结果 与A组比较,B组、D组大鼠结扎侧脊髓背角CGRP表达在术后第4、7和14天明显升高(P<0.05),C组差异无显著性。与C组比较,D组大鼠结扎侧脊髓背角CGRP表达在术后第4、7和14天明显升高(P<0.05)。而D组大鼠结扎侧脊髓背角内的CGRP表达与B组比较,差异无显著性(P>0.05)。结论 鞘内预注射L-NAME不能抑制周围神经损伤所诱导的脊髓背角CGRP表达,提示一氧化氮介导神经性疼痛的作用不是通过促进CGRP释放实现的。     

关节炎慢性吗啡耐受大鼠脊髓背角谷氨酸转运体3型的表达

目的观察谷氨酸转运体3型(EAAT3)在关节炎慢性吗啡耐受大鼠脊髓背角表达的变化。方法36只健康雄性SD大鼠随机分为六组,每组6只,行鞘内置管。其中的四组制成佐剂性关节炎模型,分别经鞘内给予生理盐水(A组)、吗啡10μg/kg(B组)、吗啡20μg/kg(C组)、吗啡10μg/kg加纳洛酮10μg/kg(D组);另外两组非致炎大鼠分别经鞘内给予生理盐水(E组)、吗啡20μg/kg(F组)。各组给药均为每日2次,连续7d。动态检测大鼠50%缩爪阈值,以免疫组化方法检测脊髓背角EAAT3表达。结果B、C组关节炎大鼠在鞘内给予吗啡第7天形成较稳定的吗啡耐受,其脊髓背角EAAT3表达下降。结论脊髓EAAT3可能参与炎性痛大鼠慢性吗啡耐受的形成机制。     

Clinical trial of esmolol-induced controlled hypotension with or without acute normovolemic hemodilution in spinal surgery

BACKGROUND: Drug-induced controlled hypotension (CH) combined with acute normovolemic hemodilution (ANH) is being widely used for blood conservation in surgical patients. The purpose of this study was to investigate the efficacy and safety of esmolol-induced CH combined with ANH (hematocrit down to 28%). METHODS: Thirty patients who were scheduled to receive spinal surgery were randomly divided into two groups: an esmolol-induced CH alone group (esmolol group, n=15) and a CH-ANH combined group (E-ANH group, n=15). Controlled hypotension was induced with esmolol 500 micro g/kg, followed by a continuous infusion of 0-300 micro g/kg/min to maintain mean arterial pressure at 55-65 mmHg. RESULTS: The mean infusion rate of esmolol in the esmolol-ANH group was 46+/-6 micro g/kg/min (mean+/-SD), which was significantly lower than the 77+/-9 micro g/kg/min used in the esmolol group (P<0.05). The number of units of homologous blood (packed RBC) transfused perioperatively was 2.2+/-0.6 units in the esmolol-ANH group, which was significantly less than 4.3+/-0.4 units used in the esmolol group (P<0.01). While O2 delivery decreased significantly during CH, O2 consumption remained unchanged in both groups. No complications resulted from CH or ANH in any of the groups. CONCLUSION: Our data suggest that ANH of moderate degree can be combined with esmolol-induced CH to improve blood conservation in surgical patients.     

艾司洛尔对患者麻醉诱导气管插管时脑电双频谱指数的影响

Objective To evaluate the effect of esmolol on bispectral index (BIS) in patients undergoing orotracheal intubation during induction of anesthesia and to investigate the mechanism of inhibiting the cardiovascular responses to tracheal intubation.Methode Forty patients in physical status of ASA Ⅰ or Ⅱ and aged 20-60 years were randomly divided into 2 groups ( n = 20 each): esmolol group (group E) and control group (group C). Anesthesia was induced with midazolam 0.1 mg/kg, fentanyl 5 μg/kg and vecuronium 0.1 mg/kg. In group E, esmolol 1 mg/kg was given intravenously before anesthesia induction and followed by an infusion of esmolol 250 μg· kg- 1·min-1, while a comparable volume of saline was given for group C. Mean arterial pressure (MAP), heart rate (HR) and BIS were recorded before esmolol administration, before induction of anesthesia, before orotracheal intubation, and at 1, 2 and 5 min after intubation, respectively.Results There were no significant differences in HR, MAP and BIS between the two groups before tracheal intubation. HR and MAP significantly increased after tracheal intubation in both groups, but BIS only in group C significantly increased after intubation.HR, MAP and BIS were significantly lower after intubation in group E than in group C ( P＜ 0.05).Conclusion Esmolol can decrease BIS during tracheal intubation and its antinociceptive property is related to the mechanism of inhibiting cardiovascular responses to tracheal intubation.     

Intrathecal landiolol inhibits nociception and spinal c-Fos expression in the mouse formalin test

PURPOSE: The purpose of this study was to determine if intrathecal landiolol, a beta1-blocker, can modulate formalin-induced nociception and spinal c-Fos expression in mice, in the absence of anesthesia. METHODS: Thirty-two mice were randomly assigned to one of four groups: the control group (n = 8) received intrathecal normal saline 10 microL, while the other three groups (n = 8 for each) received intrathecal landiolol at escalating doses of 250 microg.kg(-1), 500 microg.kg(-1) and 750 microg.kg(-1) respectively, immediately after induction of anesthesia with isoflurane. After awakening, inflammatory pain was induced by 10 microL of 5% formalin solution injected into the dorsal surface of the right hind paw. The nociceptive behaviours including licking, biting and lifting of the injected paw were cumulatively recorded as seconds of behaviours/min during phase I (0-10 min) and phase II (10-45 min). The c-Fos protein expressions in the spinal dorsal horn were detected with immunohistochemical techniques in the control and landiolol 750 microg.kg(-1) groups. RESULTS: Compared to the control group, intrathecal injection of landiolol 750 microg.kg(-1) significantly decreased pain-related behaviours in phase I, while intrathecal landiolol 250 microg.kg(-1), 500 microg.kg(-1) and 750 microg.kg(-1) significantly decreased pain-related behaviours in phase II during the formalin test. The numbers of c-Fos immunoreactive nuclei in the L5 spinal dorsal horn were significantly lower in the landiolol 750 microg.kg(-1) group compared to the control group (landiolol 750 microg.kg(-1) 2.4 +/- 1.1 vs control 9.2 +/- 3.9; P < 0.01). CONCLUSION: The present study indicates that intrathecally administered landiolol produces significant antinociceptive effects in the formalin test. Although further studies exploring the detailed mechanism are needed, these data suggest a potential role of beta1-adrenoreceptors in spinal nociceptive processing.     

艾司洛尔复合瑞芬太尼对上腹部手术患者异氟醚MAC的影响

目的 探讨艾司洛尔复合瑞芬太尼对上腹部手术患者异氟醚MAC的影响.方法 拟在全麻下行上腹部手术患者100例,随机分为5组(n=20),麻醉诱导:A组仅吸人异氟醚,其他各组在吸人异氟醚的同时,静脉输注相应剂量艾司洛尔和/或瑞芬太尼,B组静脉注射负荷量艾司洛尔1mg/kg后,以250μg·kg-1·min-1静脉输注;C组静脉注射负荷量瑞芬太尼O.25μg/kg后,以O.05 gg·kg-1·min-1静脉输注;D组和E组静脉注射负荷量瑞芬太尼0.25μg/kg后,以0.05 μg·kg-1·min-1静脉输注,同时分别静脉注射负荷量艾司洛尔O.5、1 mg/kg后,分别以50、250μg·kg-1·min-1静脉输注.意识消失后,静脉注射琥珀胆碱1.5mg/kg,气管插管后机械通气,A组仅吸入异氟醚维持麻醉,其他各组同时输注与麻醉诱导时相同剂量艾司洛尔和/或瑞芬太尼.A组和B组第1例患者异氟醚呼气末浓度为1.24%,其他各组第1例患者异氟醚呼气末浓度为0.78%,根据是否发生切皮反应,采用序贯法确定下一例患者的异氟醚呼气末浓度,相邻浓度比值为10%,计算异氟醚MAC.结果 A组、B组、c组、D组和E组异氟醚MAC分别为1.24%±0.14%、1.22%±0.09%、0.77%±0.05%、0.75%±0.06%和0.60%±0.05%;C组、D组和E组异氟醚MAC低于A组(P<0.05);E组异氟醚MAC低于C组(P<0.05).结论 静脉输注艾司洛尔250μg·kg-1·min-1复合瑞芬太尼O.05μg·kg-1·min-1可使腹部手术患者异氟醚MAC降低52%.     

尼卡地平、乌拉地尔和艾司洛尔对全麻诱导期间压力反射敏感性的影响

目的 观察尼卡地平、乌拉地尔和艾司洛尔对原发性高血压(EH)患者全麻诱导期间压力反射敏感性(BRS)的影响.方法 全身麻醉F行择期手术EH患者62例,随机分为四组,分别于诱导前2min静注尼卡地平0.5μg/kg(N组,15例)、乌拉地尔0.5 mg/kg(U组,16例)、艾司洛尔0.25 mg/kg(E组,16例)和牛理盐水(c组,15例).用相同药物进行全麻诱导.于诱导前、插管前即刻,以及插管后5、10、15、20、30 min不同时点静注硝普钠50～100μg.使SBP下降15～25mm Hg,记录SBP下降期间RR间期的变化,计算BRS.结果 N组、U组和C组插管前后各时间点BRS与基础值比较明显降低(P<0.05或P<0.01),N组中各时点BRS又明显低于C组(P<0.05),而E组明显高于C组(P<0.05).结论 伞麻诱导可降低EH患者的BRS;尼卡地平可使BRS进一步降低,乌拉地尔则无显著影响,而艾司洛尔则使伞麻诱导期的BRS升高.     

鞘内注射乙酰化酶p300抑制剂Garcinol对大鼠神经病理性痛的影响

目的观察鞘内注射乙酰化酶抑制剂Garcinol对L5脊神经结扎(spinal nerve ligation,SNL)大鼠痛觉高敏行为的影响,探讨其相关机制。方法雄性SD大鼠90只,日龄40~50d,体重180~220g。随机分为六组,每组15只。N组不做任何处理,S组仅暴露L5脊神经。C、H、M、L组大鼠行SNL手术。H、M、L组分别将Garcinol按500、100、20μg/kg溶于10μl的100%二甲基亚砜溶剂中,SNL术后第3天经鞘内导管给药,每天1次,连续给药4d。C组在相同时间鞘内注入10μl二甲基亚砜溶剂。于SNL术前1d(T0)、术后1d(T_1)、3d(T_2)、5d(T_3)、7d(T_4)、9d(T_5)、11d(T_6)、14d(T_7)测定各组大鼠热缩足潜伏期(thermal withdrawal latency,TWL)。T_4时取腰段脊髓,Western blot检测p300和乙酰化p65蛋白的表达水平,采用免疫荧光法测定脊髓背角核因子κB(NF-κB)的表达。结果 T_1~T_7时C、L、M、H组大鼠TWL明显短于N组,p300和乙酰化p65蛋白含量明显高于N组,脊髓背角NF-κB表达明显多于N组(P0.05)。T_3~T_7时M、H组大鼠TWL明显长于C组,p300和乙酰化p65蛋白含量明显低于C组,H组脊髓背角NF-κB表达明显少于C组(P0.05)。结论 p65乙酰化水平的增高参与了神经病理性痛的形成,鞘内注射乙酰化酶p300抑制剂Garcinol可以发挥镇痛作用,其机制可能与抑制p300介导的p65乙酰化,降低NF-κB表达水平有关。     

The optimal dose of esmolol and nicardipine for maintaining cardiovascular stability during rapid-sequence induction

Study ObjectiveTo determine the optimal dose of esmolol in combination with nicardipine in effectively blocking undesirable cardiovascular responses during rapid-sequence induction.DesignProspective, randomized clinical comparison study.SettingOperating room of a university hospital.Patients200 ASA physical status 1 and 2 patients requiring general anesthesia with endotracheal tube placement.InterventionsPatients were randomly allocated into one of 4 groups: Group E0 (no esmolol; control), Group E0.25 (esmolol 0.25 mg/kg), Group E0.5 (esmolol 0.5 mg/kg), and Group E1.0 (esmolol 1.0 mg/kg). All patients received 20 μg/kg of nicardipine, and esmolol was then given according to group allocation. Ninety seconds later, thiopental sodium 5 mg/kg and succinylcholine 1.0 mg/kg were injected. Endotracheal intubation was performed 60 seconds after injection of the anesthetic agents.MeasurementsSystolic (SBP), diastolic (DBP), and mean arterial (MAP) pressures; heart rate (HR), and rate-pressure product (RPP) were measured 30 seconds before and after intubation, and at 1, 3, 5, and 10 minutes after intubation. Rate changes using baseline values as the standard [rate changes = measured value/baseline value × 100 (%)] were calculated.Main ResultsSignificant attenuations in SBP, MAP, HR, and RPP after intubation were noted in the experimental groups as compared with the control group (P < 0.05). Rate changes in HR in Groups E0.5 and E1.0 were significantly lower than those in Group E0.25 immediately and one minute after intubation (P < 0.05). No difference in rate changes in HR were noted between the E0.5 and E1.0 groups.ConclusionsThe combination of nicardipine 20 μg/kg and esmolol 0.5 mg/kg most effectively attenuates the cardiovascular responses during rapid-sequence induction.     

Preemptive intrathecal ketamine injection produces a long-lasting decrease in neuropathic pain behaviors in a rat model.

BACKGROUND AND OBJECTIVES: Ketamine is an N-Methyl-D-Aspartate (NMDA) receptor antagonist, which has been found to effectively treat somatic and neuropathic pain. This study examines the effect (on neuropathic pain) of preemptive ketamine using different routes of administration (intrathecal versus intraperitoneal). METHODS: The Institutional Animal Care and Use Committee approved the study. Thirty male Sprague-Dawley rats (250-275 g) were divided into three treatment groups [intrathecal saline/intraperitoneal saline or Control (CTL), intrathecal ketamine/intraperitoneal saline (ITK), and intrathecal saline/intraperitoneal ketamine (IPK)] prior to undergoing surgery to induce neuropathic pain by tight ligation of the left L5 and L6 spinal nerves. All drugs were given 15 minutes before nerve ligation. The ITK group received intrathecal ketamine (0.5% solution, 1 mg/kg), the IPK group received intraperitoneal ketamine (0.5% solution, 1 mg/kg), saline was given in equal volume (approximately 0.05 mL). Mechanical allodynia, cold allodynia, and ongoing pain behaviors indicative of neuropathic pain were assessed on postoperative days 1, 3, 7, and 14 using validated methods. RESULTS: Compared with the CTL group, the ITK group showed a state of decreased mechanical allodynia, cold allodynia, and ongoing pain as revealed by the von Frey hair, acetone, and cold plate testing, respectively. Further, this decrease was sustained for at least 2 weeks. The IPK group showed intermediate results between the CTL and ITK. CONCLUSIONS: Neuropathic pain behaviors were significantly reduced for at least 2 weeks after intrathecal ketamine was preemptively administered to animals undergoing surgery to induce neuropathic pain. The mechanism of action is thought to be prevention of spinal cord sensitization.     

艾司洛尔对腹腔镜胆囊切除术血流动力学及内分泌的影响

目的:探讨艾司洛尔对腹腔镜手术患者手术期间血流动力学及内分泌的影响。方法:30例全麻下腹腔镜手术患者被随机分为对照组(A组,n=15)和艾司洛尔组(B组,n=15),B组于诱导时经静脉推注艾司洛尔0.5mg/kg,气腹前给予艾司洛尔0.5mg/kg,然后以50μg/kg.m in-1速度持续输注。记录A组与B组患者气腹前(T1)、气腹10m in(T2)、20m in(T3)及放气后10m in(T4)、拔管后(T5)的心率(heart rate,HR)、收缩压(systolic b lood pressure,SBP)、舒张压(d iastolic b lood pressure,DBP)、平均动脉压(m ean arterial pressure,MAP)的改变,同时测定T1~T5血中儿茶酚胺和多巴胺的浓度。结果:A组气腹期间相应时点的SBP、DBP、MAP比T1明显升高(P<0.01);T3时A组儿茶酚胺、多巴胺比T1明显增高(P<0.01),B组上述指标相应时点与T1相比无明显改变。结论:艾司洛尔能很好地稳定气腹引起的血流动力学及内分泌的变化,维持内环境稳定,同时可减少吸入异氟醚最低肺泡有效浓度,缩短拔管时间。