雷公藤甲素对糖皮质激素抵抗型支气管哮喘患者血清细胞因子水平、哮喘症状和肺功能的影响(英)

目的：观察雷公藤甲素对糖皮质激素抵抗型(SR)支气管哮喘(哮喘)患者血清细胞因子水平、哮喘症状和肺功能的影响，探讨雷公藤甲素对SR哮喘有无治疗作用。方法： SR哮喘患者16例，随机分组为A及B两组，每组各8例。2组患者均予口服丙卡特罗50~100 μg/d和茶碱400 mg/d，并急性发作时吸入沙丁胺醇 200-800 μg/d。A组患者同时联合应用雷公藤甲素每次33 μg，口服，每日3次。疗程4周。疗程开始及结束时分别行血清干扰素(IFN)-γ、白细胞介素(IL)-4、IL-5水平测定，哮喘临床积分和肺功能检查。结果： 治疗后，A组患者血清IFN-γ和肺功能指标用力肺活量(FVC%)、第1 s用力呼气容积(FEV1%)、最大呼气流量(PEF%)、50%肺活量时最大呼气流量(V50%)、25%肺活量时最大呼气流量(V25%)均显著增高，哮喘临床积分和血清IL-4、IL-5显著低于治疗前（P<0.01）和低于B组治疗后（P<0.05）。B组治疗后与治疗前比较，上述各项指标均无显著改变(P>0.05)。结论： 雷公藤甲素与丙卡特罗和茶碱联合应用可能是治疗SR哮喘的有效方法。     

鞘内应用右美托咪定改善完全弗氏佐剂诱导的大鼠慢性炎性痛行为及其机制研究

目的:观察鞘内应用右美托咪定(dexmedetomidine,DEX)对完全弗氏佐剂(complete Freund’s adjuvant,CFA)诱导的大鼠慢性炎性痛行为的改善作用并探讨其机制。方法:足底注射CFA制备大鼠慢性炎性痛模型,经鞘内给予不同剂量的DEX,采用辐射热法连续观察给药后大鼠痛行为,评价单次给药后的镇痛持续时间,并计算半数有效量(50%effective dose,ED50);旷场和转棒试验观察鞘内应用不同剂量DEX对大鼠运动功能的影响;应用免疫组织化学染色和Western Blot方法观察连续给予DEXED507 d后大鼠腰膨大平面脊髓背角星形胶质细胞活化程度。结果:鞘内应用DEX呈剂量依赖性地改善CFA诱导的大鼠辐射热痛敏且不影响运动功能;鞘内持续应用DEXED50可产生持久的镇痛效应;免疫组织化学染色和Western Blot结果均表明,与对照组相比,持续给药7 d后慢性炎性痛大鼠腰膨大平面脊髓背角星形胶质细胞的活化程度显著减轻(P0.05)。结论:鞘内应用DEX可剂量依赖性改善CFA诱导的大鼠慢性炎性痛,连续给药可产生持久的镇痛效果,其机制可能与抑制脊髓星形胶质细胞活化有关。     

吗啡镇痛对晚期肝癌患者血清TNF-α及IL-6水平影响的分析

目的考察吗啡镇痛对晚期肝癌患者血清TNF-α及IL-6水平影响。方法将120例晚期肝癌患者随机分为曲马多缓释片组和吗啡组,每组60例。曲马多缓释片组给予曲马多缓释片片口服治疗,吗啡组给予口服硫酸吗啡缓释片治疗。比较两组患者镇痛效果、不良反应和血清TNF-α及IL-6水平。结果吗啡组镇痛效果显著优于曲马多缓释片组(P<0.05)。吗啡组患者不良反应发生率显著高于曲马多缓释片组(P<0.05)。吗啡组患者镇痛后1周和1个月时血清TNF-α及IL-6水平显著低于曲马多缓释片组(P<0.05)。结论吗啡镇痛可有效降低晚期肝癌患者血清TNF-α及IL-6水平。     

曲马多、吗啡术后硬膜外自控镇痛的比较

目的观察曲马多、吗啡在术后硬膜外自控镇痛（PCEA）中的效果及不良反应。方法选择妇科手术40例,ASAⅠ-Ⅱ级采用腰-硬联合麻醉,每组20例,双盲随机分为曲马多组（A组）、吗啡组（B组）,A组镇痛液含曲马多400mg,B组镇痛液含吗啡5mg,两组溶液均加盐酸罗哌卡因100mg及氟哌利多5mg,加生理盐水稀释至100ml,均采用负荷剂量＋持续剂量给药模式。术后观察记录48h内疼痛视觉模拟评分及病人主观不适。结果B组镇痛效果要好于A组,但差异无显著性意义P〉0．05,B组与A组相比恶心、呕吐、皮肤瘙痒等副作用发生率高差异有显著意义P〈0．05。结论4％曲马多配伍长效局麻药加氟哌利多用于硬膜外术后镇痛,具有镇痛效果好、副作用少等优点。     

布托啡诺抑制TLR4/MyD88/NF-κB信号通路对卵巢癌细胞增殖、凋亡、迁移和侵袭的影响

目的 探讨布托啡诺抑制Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核因子-κB(NF-κB)信号通路对卵巢癌细胞增殖、凋亡、迁移和侵袭的影响。方法 实验分组1:(2.5、5.0、10、20、40、80、160、320)μg/mL布托啡诺处理人卵巢癌细胞A2780,计算细胞半数抑制浓度（IC50）。实验分组2：对照组（正常培养）、布托啡诺组（13.24μg/mL布托啡诺）、布托啡诺+LPS组（13.24μg/mL布托啡诺+1μg/mL LPS）,CCK-8检测细胞增殖情况;流式细胞术检测细胞凋亡情况;Transwell检测细胞侵袭和迁移情况;蛋白质免疫印迹检测细胞中TLR4、MyD88、NF-κB蛋白表达情况。结果 细胞IC50为13.24μg/mL。与对照组相比,布托啡诺组细胞OD450水平、迁移和侵袭数量、细胞中TLR4、MyD88、NF-κB蛋白水平降低（P<0.05）,细胞凋亡率升高（P<0.05）;与布托啡诺组相比,布托啡诺+LPS组细胞OD450水平、迁移和侵袭数量、细胞中TLR4、MyD88、NF-κB蛋白水平升高（P<0.05）,细胞凋...     

鞘内注射米贝地尔对神经痛大鼠脊髓nNOS表达的影响

目的：探讨脊髓T型钙通道在背根节慢性压迫（CCD）痛中的作用以及其对脊髓背角神经元神经型一氧化氮合酶（nNOS）表达的影响。方法: 行为学部分，SD大鼠48只，随机分为6组，每组8只，即sham组、CCD组、CCD+生理盐水组；CCD+米贝地尔50 μg组；CCD+米贝地尔100 μg组；CCD+米贝地尔200 μg组，sham组和CCD组在术前、术后1、3、5、7、14、21 d分别测定大鼠机械和热痛敏，其余各组在手术后5 d分别鞘内注射盐水、米贝地尔各个剂量，分别在术前、给药前、给药后30 min、60 min、120 min、240 min、480 min分别测定大鼠机械和热痛敏。免疫组化部分，设正常对照组（normal），其余分组同行为学部分,每组6只。Normal、sham组和CCD组大鼠术后5 d处死，其余各组动物在术后第5 d鞘内单次给药后2 h处死，取脊髓腰膨大做免疫组织化学实验。结果: CCD大鼠在手术后形成稳定的痛敏，鞘内单次注射米贝地尔各个剂量能抑制大鼠痛敏，并持续到给药后240 min。CCD大鼠术后5 d脊髓背角浅层nNOS阳性神经元明显增多，鞘内注射米贝地尔能抑制神经元nNOS的表达。结论：脊髓T型钙通道参与CCD大鼠机械和热痛敏的形成，且可能与脊髓背角神经元nNOS的表达有关。     

一氧化氮对慢性缺氧高二氧化碳大鼠肺血管尾加压素Ⅱ的影响

目的： 探讨一氧化氮/L-精氨酸（NO/L-Arg）系统和尾加压素Ⅱ（UⅡ）在大鼠慢性缺氧（O2）高二氧化碳（CO2）肺动脉高压病理过程的作用及关系。 方法： 40只大鼠随机分成4组（每组各10只）：正常对照组（A组）、慢性缺O2高CO2 加生理盐水4周组（B组）、慢性缺O2高CO2 加L-Arg脂质体4周组（C组）、慢性缺O2高CO2 加N-硝基-L-精氨酸甲酯（L-NAME）4周组（D组）。免疫组化法和组织原位杂交法检测肺小动脉UⅡ和UⅡ mRNA、UⅡ受体（UT）mRNA的表达，并观察肺小动脉显微结构的变化。 结果： （1）肺动脉平均压(mPAP)、右心室(RV)和左心室+室间隔(LV+S)重量比值［RV/(LV+S)］:Ｂ组高于A组（均P<0.05）；C组低于B组（均P<0.01）；D组两指标不仅高于A组（P<0.01和<0.05），且mPAP也高于B组（P<0.01）。（2）肺小动脉管壁面积/管总面积（WA/TA）和中膜厚度（PAMT）：B组显著大于A组（P<0.05）；C组与B组的差异也有显著性（P<0.01）；而D组WA/TA也显著高于A组。（3）肺小动脉UⅡ、UⅡ mRNA、UT mRNA表达：同A组比较，Ｂ组、D组各指标都显著增高（均P<0.01）；C组UⅡ、UⅡ mRNA的表达较Ｂ组明显下调（P<0.01），同A组比较，其UⅡ表达下调但UT mRNA表达增加（均P<0.01）；D组UⅡ表达较Ｂ组低，而UT mRNA表达较Ｂ组高（均P<0.01）。 结论： 慢性缺O2高CO2肺动脉高压的发生发展可能与UⅡ的异常表达增加有关，而外源性NO可能有抑制UⅡ的作用。     

丁丙诺啡用于妇科手术后静脉自控镇痛的临床观察

目的探讨丁丙诺啡在妇科手术后病人自控静脉镇痛（PCIA）的效果和不良反应。方法80例妇科腹部手术患者随机分为丁丙诺啡组（A组）和芬太尼组（B组）,每组40例,在手术后接受PCIA。术后采用视觉模拟评分法（VAS）、Ramsay镇静评分法评估镇静、镇痛效果,观察不良反应、记录患者对PCIA的满意度。结果丁丙诺啡组VAS评分、Ramsay评分均低于芬太尼组（P〈0.05）,两组患者的满意度和不良反应发生率均无显著性差异（P〉0.05）。结论由于丁丙诺啡镇痛效果强、副作用相对较少,在妇科腹部手术后PCIA的效果优于芬太尼,值得推广。     

大鼠脊髓内大麻素CB2受体在芍药苷拮抗吗啡镇痛耐受中的作用

目的:探讨脊髓内大麻素CB2受体在芍药苷拮抗大鼠慢性吗啡镇痛耐受中的作用。方法:成功鞘内置管清洁级Sprague-Dawley(SD)大鼠60只,随机分为4组(n=15):生理盐水组(NS组),吗啡组(MOR组),芍药苷组(PF组)和吗啡+芍药苷组(MOR+PF组)。连续7 d鞘内注射吗啡(15μg)建立慢性吗啡耐受的动物模型。采用50℃热水甩尾潜伏期法(tail flick latency,TFL)和机械反射阈值法(mechanical withdrawal threshold,MWT)观察鞘内注射芍药苷对吗啡镇痛耐受的影响;应用免疫组织荧光染色法检测芍药苷对腰段脊髓小胶质细胞活化的影响;应用免疫印迹法检测芍药苷对腰段脊髓CB2表达的影响。结果:连续7 d鞘内注射吗啡后,与NS组比较,MOR组大鼠腰段脊髓背角小胶质细胞显著增多,腰段脊髓CB2表达显著增加(P0.05);而与MOR组比较,MOR+PF组大鼠腰段脊髓背角小胶质细胞显著减少,腰段脊髓CB2表达显著减少(P0.05)。与MOR组7 d大鼠最大镇痛效应百分率(percent of maximal possible potential effect,MPE)比较,MOR+PF组大鼠MPE显著增加(TFL:19%±4%vs 41%±3%;MWT:18%±6%vs 42%±4%,P0.05)。结论:芍药苷能显著拮抗大鼠慢性吗啡镇痛耐受,其作用机制可能与抑制脊髓内CB2受体表达增加有关。     

多模型迭代重建在CT门静脉成像中改善图像质量的应用

目的:探讨多模型迭代重建（ASIR-V）在CT门静脉成像（CTPV）中改善图像质量的应用价值。方法:收集Revolution CT检查CTPV患者60例并随机分为A、B组。两组均采用管电压120 kV、噪声指数10、对比剂用量450 mgI/kg。扫描结束后,A组采用40%ASIR,B组采用40%ASIR-V。分别测量门静脉主干、门静脉左支、门静脉右支的CT值和CT值标准差,并计算信噪比和对比噪声比。记录两组患者CT容积剂量指数（CTDIVOL）、剂量长度乘积（DLP）,并计算有效辐射剂量（ED）。由两名有经验放射科医师采用5分法标准对图像质量进行双盲法主观评分。结果:两组患者一般资料、辐射剂量（CTDIVOL、DLP、ED）和对比剂总量间差异无统计学意义（P>0.05）。两组门静脉主干、门静脉左支及右支CT值均无统计学差异（P>0.05）。A组门静脉主干、门静脉左支及右支CT值的标准差高于B组,A组信噪比和对比噪声比低于B组,且差异均具有统计学意义（P<0.05）。两名医师对两组图像主观评分具有很好的一致性（Kappa值>0.75, P<0.05）,B组图像主观评分显著高于A组（P<0.05）。结论:ASIR-V可以显著提高门静脉图像质量,为临床诊断提供更好的CTPV图像。     

The effects of serotonin/norepinephrine reuptake inhibitors and serotonin receptor agonist on morphine analgesia and tolerance in rats

Several studies have demonstrated that serotonergic and noradrenergic systems have important roles in morphine analgesia and tolerance. However, the exact mechanism underlying the development of morphine tolerance is not fully understood. The aim of this study was to investigate the possible role of serotonin/norepinephrine reuptake inhibitors (amitriptyline, venlafaxine) and serotonin receptor (5-HT(1A) and 5-HT(1B/1D)) agonist (dihydroergotamine) in morphine analgesia and tolerance in rats. To constitute morphine tolerance, animals received morphine (50 mg/kg; s.c.) once daily for 3 days. After the last dose of morphine was injected on day 4, morphine tolerance was evaluated. The analgesic effects of amitriptyline (20 mg/kg; i.p.), venlafaxine (20 mg/kg; s.c.), dihydroergotamine (100 μg/kg; i.v.) and morphine (5 mg/kg) were considered at 15- to 30-min intervals (0, 15, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests. In this study, the data obtained suggested that amitriptyline and venlafaxine significantly increased the analgesic effect of morphine and attenuated the expression of morphine tolerance. However, dihydroergotamine significantly increased the analgesic effect of morphine but did not reduce the expression of morphine tolerance. In conclusion, we determined that co-administration of morphine with amitriptyline and venlafaxine increased the analgesic effects of morphine and attenuated the morphine analgesic tolerance.     

Ultra-low dose naloxone restores the antinociceptive effect of morphine in pertussis toxin–treated rats and prevents glutamate transporter downregulation by suppressing the p38 mitogen-activated protein kinase signaling pathway

We previously demonstrated that ultra-low dose naloxone restores the antinociceptive effect of morphine in rats with pertussis toxin (PTX)–induced thermal hyperalgesia by reversing the downregulation of glutamate transporter (GT) expression and suppressing spinal neuroinflammation. In the present study, we examined the underlying mechanisms of this anti-inflammatory effect in PTX-treated rats, particularly on the expression of GTs. Male Wistar rats were implanted with an intrathecal catheter and, in some cases, with a microdialysis probe. All rats were injected intrathecally with saline (5 μl) or PTX (1 μg), then, 4 days later, were randomly assigned to receive a single injection of saline, ultra-low dose naloxone (15 ng), or the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (5 μg), followed by morphine injection (10 μg) 30 min later. Our results showed that PTX injection induced activation of microglia and a significant increase in P-p38 MAPK expression in the spinal cord. Ultra-low dose naloxone plus morphine significantly inhibited the effect of PTX on P-p38 MAPK expression in the spinal cord, while the p38 MAPK inhibitor SB203580 attenuated the PTX-induced mechanical allodynia, thermal hyperalgesia, increase in spinal cerebrospinal fluid excitatory amino acids, and downregulation of GTs. These results show that the restoration of the antinociceptive effect of morphine and GT expression in PTX-treated rats by ultra-low dose naloxone involves suppression of the p38 MAPK signal transduction cascade.     

Effects of intrathecal morphine on the ventilatory response to hypoxia

BACKGROUND: Intrathecal administration of morphine produces intense analgesia, but it depresses respiration, an effect that can be life-threatening. Whether intrathecal morphine affects the ventilatory response to hypoxia, however, is not known. METHODS: We randomly assigned 30 men to receive one of three study treatments in a double-blind fashion: intravenous morphine (0.14 mg per kilogram of body weight) with intrathecal placebo; intrathecal morphine (0.3 mg) with intravenous placebo; or intravenous and intrathecal placebo. The selected doses of intravenous and intrathecal morphine produce similar degrees of analgesia. The ventilatory response to hypercapnia, the subsequent response to acute hypoxia during hypercapnic breathing (targeted end-tidal partial pressures of expired oxygen and carbon dioxide, 45 mm Hg), and the plasma levels of morphine and morphine metabolites were measured at base line (before drug administration) and 1, 2, 4, 6, 8, 10, and 12 hours after drug administration. RESULTS: At base line, the mean (+/-SD) values for the ventilatory response to hypoxia (calculated as the difference between the minute ventilation during the second full minute of hypoxia and the fifth minute of hypercapnic ventilation) were similar in the three groups: 38.3+/-23.2 liters per minute in the placebo group, 33.5+/-16.4 liters per minute in the intravenous-morphine group, and 30.2+/-11.6 liters per minute in the intrathecal-morphine group (P=0.61). The overall ventilatory response to hypoxia (the area under the curve) was significantly lower after either intravenous morphine (20.2+/-10.8 liters per minute) or intrathecal morphine (14.5+/-6.4 liters per minute) than after placebo (36.8+/-19.2 liters per minute) (P=O.003). Twelve hours after treatment, the ventilatory response to hypoxia in the intrathecal-morphine group (19.9+/-8.9 liters per minute), but not in the intravenous-morphine group (30+/-15.8 liters per minute), remained significantly depressed as compared with the response in the placebo group (40.9+/-19.0 liters per minute) (P= 0.02 for intrathecal morphine vs. placebo). Plasma concentrations of morphine and morphine metabolites either were not detectable after intrathecal morphine or were much lower after intrathecal morphine than after intravenous morphine. CONCLUSIONS: Depression of the ventilatory response to hypoxia after the administration of intrathecal morphine is similar in magnitude to, but longer-lasting than, that after the administration of an equianalgesic dose of intravenous morphine.     

Investigation of tolerance to chronic intrathecal morphine infusion in the rat

Rats received chronic subcutaneous or intrathecal infusions of either saline or 25 micrograms/microliter/hr or 50 micrograms/microliter/hr of morphine sulfate. During five days of infusion individual groups of rats were assessed on either the nociceptive tail flick or hot plate test. After the infusions, the analgesic effects of either subcutaneous or intrathecal morphine test doses were evaluated. Tolerance developed to the analgesic effect of both subcutaneous and intrathecal morphine infusions on the tail flick test. Subcutaneously infused rats were also tolerant to a subcutaneous morphine challenge on this test. However, intrathecally infused rats were not tolerant to either the subcutaneous or intrathecal challenge. In contrast to these results, rats tested on the hot plate were not analgesic in response to either subcutaneous or intrathecal morphine infusions. However, these rats were tolerant when challenged with either subcutaneous or intrathecal morphine. The results are discussed in terms of the relative contribution of spinal and supraspinal sites to opiate tolerance, and the possibility that tolerance does not develop to the antinociceptive effect of spinal morphine on spinally mediated reflexes.     

Ultra-low dose naloxone restores the antinociceptive effect of morphine in pertussis toxin-treated rats by reversing the coupling of μ-opioid receptors from Gs-protein to coupling to Gi-protein

Pertussis toxin (PTX) treatment results in ADP-ribosylation of Gi-protein and thus in disruption of μ-opioid receptor signal transduction and loss of the antinociceptive effect of morphine. We have previously demonstrated that pretreatment with ultra-low dose naloxone preserves the antinociceptive effect of morphine in PTX-treated rats. The present study further examined the effect of ultra-low dose naloxone on μ-opioid receptor signaling in PTX-treated rats and the underlying mechanism. Male Wistar rats implanted with an intrathecal catheter received an intrathecal injection of saline or PTX (1 μg in 5 μl of saline), then, 4 days later, were pretreated by intrathecal injection with either saline or ultra-low dose naloxone (15 ng in 5 μl of saline), followed, 30 min later, by saline or morphine (10 μg in 5 μl of saline). Four days after PTX injection, thermal hyperalgesia was observed, together with increased coupling of excitatory Gs-protein to μ-opioid receptors in the spinal cord. Ultra-low dose naloxone pretreatment preserved the antinociceptive effect of morphine, and this effect was completely blocked by the μ-opioid receptor antagonist CTOP, but not by the κ-opioid receptor antagonist nor-BNI or the δ-opioid receptor antagonist naltrindole. Moreover, a co-immunoprecipitation study showed that ultra-low dose naloxone restored μ-opioid receptor/Gi-protein coupling and inhibited the PTX-induced μ-opioid receptor/Gs-protein coupling. In addition to the anti-neuroinflammatory effect and glutamate transporter modulation previously observed in PTX-treated rats, the re-establishment of μ-opioid receptor Gi/Go-protein coupling is involved in the restoration of the antinociceptive effect of morphine by ultra-low dose naloxone pretreatment by normalizing the balance between the excitatory and inhibitory signaling pathways. These results show that ultra-low dose naloxone preserves the antinociceptive effect of morphine, suppresses spinal neuroinflammation, and reduces PTX-elevated excitatory Gs-coupled opioid receptors in PTX-treated rats. We suggest that ultra-low dose naloxone might be clinically valuable in pain management.     

Interaction of morphine and selective serotonin receptor inhibitors in rats experiencing inflammatory pain

Citalopram and paroxetine are selective serotonin reuptake inhibitors and also have antinociceptive effects. We investigated the antiallodynic and antihyperalgesic effects of intrathecally administered morphine, citalopram, paroxetine, and combinations thereof, in a rat model in which peripheral inflammation was induced by complete Freund's adjuvant (CFA). Drugs were intrathecally administered via direct lumbar puncture. Mechanical allodynia was measured using a Dynamic Plantar Aesthesiometer. Thermal hyperalgesia and cold allodynia were determined by measuring latency of paw withdrawal in response to radiant heat and cold water. Behavioral tests were run before and 15, 30, 45, and 60 min after intrathecal injection. Intraplantar injection of CFA produced mechanical allodynia, thermal hyperalgesia, and cold allodynia. Intrathecally administered morphine (0.3 or 1 μg) had antiallodynic or antihyperalgesic effects (24.0%-71.9% elevation). The effects of morphine were significantly increased when a combination of citalopram (100 μg) and paroxetine (100 μg) was added (35.2%-95.1% elevation). This rise was reversed by naloxone and methysergide. The effects of citalopram and paroxetine were also reversed by naloxone and methysergide. We suggest that the mu opioid receptor and serotonin receptors play major roles in production of the antiallodynic and antihyperalgesic effects of morphine, citalopram, paroxetine, and combinations thereof, in animals experiencing inflammatory pain.     

Intrathecal Morphine Plus General Anesthesia in Cardiac Surgery: Effects on Pulmonary Function, Postoperative Analgesia, and Plasma Morphine Concentration

OBJECTIVES:

To evaluate the effects of intrathecal morphine on pulmonary function, analgesia, and morphine plasma concentrations after cardiac surgery.

INTRODUCTION:

Lung dysfunction increases morbidity and mortality after cardiac surgery. Regional analgesia may improve pulmonary outcomes by reducing pain, but the occurrence of this benefit remains controversial.

METHODS:

Forty-two patients were randomized for general anesthesia (control group n=22) or 400 μg of intrathecal morphine followed by general anesthesia (morphine group n=20). Postoperative analgesia was accomplished with an intravenous, patient-controlled morphine pump. Blood gas measurements, forced vital capacity (FVC), forced expiratory volume (FEV), and FVC/FEV ratio were obtained preoperatively, as well as on the first and second postoperative days. Pain at rest, profound inspiration, amount of coughing, morphine solicitation, consumption, and plasma morphine concentration were evaluated for 36 hours postoperatively. Statistical analyses were performed using the repeated measures ANOVA or Mann-Whiney tests (*p<0.05).

RESULTS:

Both groups experienced reduced FVC postoperatively (3.24 L to 1.38 L in control group; 2.72 L to 1.18 L in morphine FEV₁ (p=0.085), group), with no significant decreases observed between groups. The two groups also exhibited similar results for FEV₁/FVC (p=0.68) and PaO₂/FiO₂ ratio (p=0.08). The morphine group reported less pain intensity (evaluated using a visual numeric scale), especially when coughing (18 hours postoperatively: control group= 4.73 and morphine group= 1.80, p=0.001). Cumulative morphine consumption was reduced after 18 hours in the morphine group (control group= 20.14 and morphine group= 14.20 mg, p=0.037). The plasma morphine concentration was also reduced in the morphine group 24 hours after surgery (control group= 15.87 ng.mL⁻¹ and morphine group= 4.08 ng.mL⁻¹, p=0.029).

CONCLUSIONS:

Intrathecal morphine administration did not significantly alter pulmonary function; however, it improved patient analgesia and reduced morphine consumption and morphine plasma concentration.     

Adolescent morphine exposure increases nociceptive behaviors in rat model of formalin test

The number of adolescents who use illicit drugs has increased dramatically. Adolescence is a critical period for brain development and maturation. The importance of the study of pain perception and the possible mechanisms involved is crystal clear. Up until now, there has been no evidence regarding the long-term effect of adolescence morphine administration on pain perception. The objective of the present study was to investigate long-lasting effect of adolescent morphine exposure on pain perception as well as analgesic response to a single dose of morphine injection. Adolescent and adult rats received morphine or saline, and then after 30 days of washout period, formalin test was performed. To evaluate morphine analgesia, in a separate group of animals, formalin test was performed after injection of a single dose of morphine during adulthood. The results demonstrated that the adolescent rats treated by morphine exhibited higher pain-related behaviors compared to the control group, while the same results were not observed in adult rats that had been treated by morphine. Moreover, there was no significant difference in analgesic response to a single dose of morphine between two experimental groups. This study demonstrates enduring effect of morphine exposure during adolescence on pain perception.     

Akt通路及细胞凋亡在瘦素介导的大鼠慢性吗啡镇痛耐受中的作用

目的:探讨Akt(又称蛋白激酶B)及活化的caspase-3在瘦素介导的大鼠慢性吗啡镇痛耐受中的作用。方法:在SD大鼠建立慢性吗啡镇痛耐受模型;采用Western blotting法测定脊髓Akt和cleaved caspase-3的水平;免疫组织化学染色法检测脊髓磷酸化Akt(p-Akt)及cleaved caspase-3阳性细胞;免疫双染检测p-Akt及cleaved caspase-3阳性细胞的定位。结果:鞘内慢性注射吗啡(15μg)7 d可明显上调大鼠脊髓p-Akt及cleaved caspase-3的蛋白水平;在注射吗啡前30 min,鞘内注射瘦素拮抗剂(3μg)7 d能显著地抑制慢性吗啡处理对p-Akt和cleaved caspase-3的上调作用;p-Akt只定位在脊髓神经元,而cleaved caspase-3仅定位在星形胶质细胞;瘦素拮抗剂、Akt抑制剂及caspase-3抑制剂均能抑制慢性吗啡镇痛耐受。结论:脊髓Akt通路及活化的caspase-3参与瘦素介导的大鼠慢性吗啡镇痛耐受。     

急、慢性吗啡处理对大鼠大脑皮层tau蛋白和神经微丝磷酸化水平的影响

目的:观察急、慢性吗啡处理对大鼠大脑皮质细胞骨架蛋白磷酸化水平的影响,探讨吗啡导致细胞周期依赖性蛋白激酶-5(cyclin dependent kinase-5,CDK5)过度表达与细胞骨架蛋白过度磷酸化的关系。方法:雄性SD大鼠40只,随机均分为急性对照组、急性吗啡处理组、慢性对照组、慢性吗啡处理组。急性吗啡处理组腹腔注射吗啡30mg/kg1次,慢性吗啡处理组腹腔注射吗啡10mg/kg,每天2次(时间8:00、20:00)共10d。采用免疫印迹法测定大鼠大脑皮质tau蛋白和神经微丝的磷酸化水平及CDK5、p35表达水平。结果:(1)与急性对照组比较,急性吗啡处理组tau蛋白和神经微丝磷酸化水平升高,CDK5的表达增加;(2)与慢性对照组比较,慢性吗啡处理组tau蛋白和神经微丝磷酸化水平升高,CDK5的表达无明显变化;(3)与急性吗啡处理组比较,慢性吗啡处理组tau蛋白和神经微丝蛋白磷酸化水平降低;(4)各组间p35表达水平无明显改变。结论:急、慢性吗啡处理可导致大鼠大脑皮质tau蛋白和神经微丝的异常过度磷酸化,但这种变化可能与CDK5的过度表达无关。