硬膜外腔单次注射吗啡联合地佐辛静脉用于剖宫产术后镇痛的疗效及对患者血清5-羟色胺、泌乳素水平的影响

目的:探讨硬膜外腔单次注射吗啡联合地佐辛静脉用于剖宫产术后镇痛的疗效及对患者血清5-羟色胺、泌乳素水平的影响。方法:选择2016年1月至2018年11月择期进行剖宫产的产妇80例,按照随机数字法将其分为观察组和对照组,每组各40例。对照组采用硬膜外腔单次注射吗啡自控镇痛,观察组采用硬膜外腔单次注射吗啡联合地佐辛静脉自控镇痛。采用视觉模拟评分法(VAS)评估两组产妇术后镇痛效果,酶联免疫法及化学发光法分别测定产妇术前、术后6 h、12 h、24 h和48 h血清5-羟色胺水平及泌乳素水平,并观察两组产妇术后不良反应的发生情况。结果:两组产妇患者术后VAS评分随着时间延长逐渐降低,观察组术后第6 h、12 h、24 h以及48 h的VAS评分均显著低于对照组(P0.05);两组产妇术后血清5-羟色胺水平均较术前明显降低(P0.05),而血清泌乳素均较术前显著升高(P0.05),且观察组术后第6 h、12 h、24 h以及48 h血清5-羟色胺水平均显著低于对照组(P0.05),而血清泌乳素浓度均明显高于对照组(P0.05)。两组产妇患者术后均未出现呼吸抑制,对照组恶心(Nausea)、呕吐、头晕、皮肤瘙痒的发生率明显低于对照组(P0.05)。结论:硬膜外腔单次注射吗啡联合地佐辛静脉用于剖宫产术后镇痛疗效及安全性均较硬膜外腔单次注射吗啡自控镇痛更好,产妇术后血清泌乳素及5-羟色胺浓度显著提高,对于产后抑郁的发病可能有一定的抑制作用,也有利于产妇术后恢复,尽早哺乳。     

Positive and Negative Allosteric Modulation of an α1β3γ2 γ-Aminobutyric Acid Type A (GABAA) Receptor by Binding to a Site in the Transmembrane Domain at the γ+-β? Interface

In the process of developing safer general anesthetics, isomers of anesthetic ethers and barbiturates have been discovered that act as convulsants and inhibitors of γ-aminobutyric acid type A receptors (GABA_ARs) rather than potentiators. It is unknown whether these convulsants act as negative allosteric modulators by binding to the intersubunit anesthetic-binding sites in the GABA_AR transmembrane domain (Chiara, D. C., Jayakar, S. S., Zhou, X., Zhang, X., Savechenkov, P. Y., Bruzik, K. S., Miller, K. W., and Cohen, J. B. (2013) J. Biol. Chem. 288, 19343–19357) or to known convulsant sites in the ion channel or extracellular domains. Here, we show that S-1-methyl-5-propyl-5-(m-trifluoromethyl-diazirynylphenyl) barbituric acid (S-mTFD-MPPB), a photoreactive analog of the convulsant barbiturate S-MPPB, inhibits α1β3γ2 but potentiates α1β3 GABA_AR responses. In the α1β3γ2 GABA_AR, S-mTFD-MPPB binds in the transmembrane domain with high affinity to the γ⁺-β⁻ subunit interface site with negative energetic coupling to GABA binding in the extracellular domain at the β⁺-α⁻ subunit interfaces. GABA inhibits S-[³H]mTFD-MPPB photolabeling of γ2Ser-280 (γM2–15′) in this site. In contrast, within the same site GABA enhances photolabeling of β3Met-227 in βM1 by an anesthetic barbiturate, R-[³H]methyl-5-allyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (mTFD-MPAB), which differs from S-mTFD-MPPB in structure only by chirality and two hydrogens (propyl versus allyl). S-mTFD-MPPB and R-mTFD-MPAB are predicted to bind in different orientations at the γ⁺-β⁻ site, based upon the distance in GABA_AR homology models between γ2Ser-280 and β3Met-227. These results provide an explanation for S-mTFD-MPPB inhibition of α1β3γ2 GABA_AR function and provide a first demonstration that an intersubunit-binding site in the GABA_AR transmembrane domain binds negative and positive allosteric modulators.     

Overexpression of lncRNA Gm15621 alleviates apoptosis and inflammation response resulting from sevoflurane treatment through inhibiting miR-133a/Sox4

Sevoflurane is the most widely used anesthetic administered by inhalation. Exposure to sevoflurane can elicit learning deficits and abnormal cognitive disorder. In this study, we investigated the function of long noncoding RNA (lncRNA) Gm15621. Primary hippocampal neuron cells were used to analyze the function of lncRNA Gm15621 in vitro. The tunel, inflammation markers, and cell survival rates were detected to evaluate the function of lncRNA Gm15621. Dual-luciferase reporter assay was used to identify the interaction between microRNA 133a and Gm15621. We found that lncRNA Gm15621 located in the cytoplasm. The expression of lncRNA Gm15621 was decreased with the development of sevoflurane exposure. Overexpression of lncRNA Gm15621 significantly reduced the apoptosis and cell survival rates. The inflammation response was also attenuated in lncRNA Gm15621 overexpressed group. The dual-luciferase assay revealed that miR-133a was the direct target of lncRNA Gm15621. In addition, we also found that Sox4 was a downstream target of miR-133a and lncRNA Gm15621 exerted its biological functions by regulating the expression of Sox4. In summary, our findings revealed that lncRNA Gm15621 ameliorated the sevoflurane-induced neurotoxicity and the important role of Gm15621/miR-133a/Sox4 axis in cognitive disorder.     

超声引导下髂腹下－髂腹股沟神经阻滞应用于男性全身麻醉后导尿管相关膀胱刺激征临床效果的回顾性研究

摘要 目的：探讨超声引导髂腹下－髂腹股沟神经阻滞应用于男性全身麻醉后导尿管相关膀胱刺激征（CRBD）的临床效果。方法：回顾性分析本院收治的60例择期全身麻醉下行下肢清创、皮瓣转移或植皮的男性患者,且术中需留置导尿管者的临床资料。按是否行超声引导下髂腹下－髂腹股沟神经阻滞分为观察组和对照组,观察组在全身麻醉后,超声引导下进行双侧髂腹下-髂腹股沟神经阻滞,神经阻滞完成后行导尿管留置术。对照组麻醉诱导完成后,即行导尿管留置术。记录拔除气管导管后10 min（T1）、1h（T2）、3h（T3）CRBD严重程度评分和Riker镇静-躁动评分。记录术前（T0）和T1、T2、T3对应时点的收缩压（SBP）、舒张压（DBP）、心率（HR）,对比两组的苏醒质量和麻醉相关不良反应。结果：术后各时段观察组CRBD严重程度评分和Riker镇静-躁动评分均明显低于对照组（P＜0.05）;术后各时段观察组的SBP、DBP、HR与对照组相比均明显降低 （P＜0.05）;观察组PACU内非计划性使用镇痛药、非计划性拔除尿管的比例低于对照组,PACU的停留时间短于对照组（P <0.05）;两组麻醉相关不良反应发生率对比未见统计学意义（P >0.05）。结论：超声引导下髂腹下－髂腹股沟神经阻滞操作简便,减轻全身麻醉后CRBD的效果确切,患者对导尿管有良好的耐受,术后血流动力学和循环更稳定,苏醒质量更高。     

不同剂量阿芬太尼复合罗哌卡因椎管内麻醉对肛肠手术术中及术后尿潴留的影响

摘要 目的：探讨不同剂量阿芬太尼复合罗哌卡因椎管内麻醉对肛肠手术术中及术后尿潴留的影响。方法：选取我院2020年4月到2020年12月共收治的100例肛肠手术患者作为研究对象,将患者随机分为A组、B组和C组,A组30例,B组30例,C组40例。所有患者均行阿芬太尼复合罗哌卡因椎管内腰硬联合麻醉,其中A组患者阿芬太尼剂量为1 μg/kg,B组为5 μg/kg,C组为10 μg/kg,对比三组患者麻醉效果,对比三组患者麻醉前、麻醉后、手术1 h后的平均动脉压（MAP）、心率（HR）、心脏指数（CI）、每搏指数（SVI）和每搏变异度（SVV）变化情况,术后1 h、术后2 h、术后3 h和术后6 h的VAS评分以及术后不良反应和尿潴留发生率。结果：通过对比三组患者麻醉效果发现,A组患者优良率为80.00%,B组患者优良率为100.00%,C组患者优良率为100.00%,C组高于A组和B组（P＜0.05）;麻醉前三组患者的SVV、SVI、CI、MAP、HR对比无明显差异（P＞0.05）,麻醉后三组患者SVV、CI对比无明显差异（P＞0.05）,但三组患者的SVI、MAP、HR对比差异显著,C组明显高于A组和B组（P＜0.05）,手术1 h后,三组患者的SVV、SVI对比无明显差异（P＞0.05）,但两者CI、MAP、HR对比差异显著,C组高于于A组和B组（P＜0.05）;通过对比三组患者术后不同时间VAS评分发现,三组患者术后6 h的 VAS评分对比无明显差异（P＞0.05）,术后1 h、术后2 h、术后3 h三组患者VAS评分对比差异显著,C组明显低于A组和B组;C组患者嗜睡、恶心呕吐、肛门下坠感等术后不良反应对比无明显差异（P＞0.05）,C组患者术后尿潴留发生率明显低于B组和A组,组间对比,差异具有统计学意义（P＜0.05）。结论：5 μg/kg与10 μg/kg阿芬太尼复合罗哌卡因椎管内麻醉对肛肠手术患者均具有非常好的麻醉效果,但是应用剂量为10 μg/kg阿芬太尼符合罗哌卡因能够稳定患者血流动力学指标,降低患者应激反应,而且术后具有一定的阵痛效果,安全性好,且能够减少患者术后尿储留的发生情况,值得临床应用推广。     

腰硬联合蛛网膜下腔注射芬太尼用于分娩镇痛的半数有效剂量的临床研究

目的:确定腰硬联合蛛网膜下腔注射芬太尼用于分娩镇痛的半数有效剂量(ED50),观察蛛网膜下腔注射半数有效剂量芬太尼的效果和副作用,并与蛛网膜下腔注射半数有效剂量的布比卡因进行对比。方法:首先,确定芬太尼用于分娩镇痛的半数有效剂量,筛选50例符合的产妇行腰硬联合分娩镇痛,蛛网膜下腔注射芬太尼的剂量始于25μg,如果镇痛有效,下一病例减少2.5μg芬太尼;如果无效则下一病例增加2.5μg芬太尼。用Probit回归分析计算芬太尼蛛网膜下腔注射行分娩镇痛的半数有效剂量和95%可信区间(95%CI)。第二步,筛选100例需要进行分娩镇痛的产妇,随机分入ED50芬太尼组(F组)和ED50布比卡因组(B组),比较两组药物镇痛效果及起效时间、产妇下肢运动阻滞程度及血压心率变化、胎心变化和镇痛全程药物追加次数。结果:芬太尼蛛网膜下腔注射分娩镇痛的ED50为11.5μg,95%CI为3.5-15.4μg。F组镇痛的平均起效时间为(12.0±3.8)min,两组镇痛的成功率没有统计学差异(P=0.218),F组需要追加PCA的病例百分率明显少于B组(P=0.018)。F组下肢运动阻滞程度轻于B组(P=0.018)。两组镇痛方法对产妇的血压、心率均无明显影响。两组胎心下降的发生率没有明显差异(P0.05)。F组皮肤瘙痒的发生率明显增加(P=0.000)。结论:腰硬联合分娩镇痛蛛网膜下腔注射芬太尼的ED50为11.5μg,95%CI为3.5-15.4μg。蛛网膜下腔注射半数有效剂量的芬太尼可以提供简便、持久、满意和安全的镇痛效果,并且对下肢运动阻滞程度较小,但其所致皮肤瘙痒的发生率升高。     

腰麻硬膜外联合麻醉与硬膜外麻醉对剖宫产患者血流动力学的影响

目的:探讨腰麻硬膜外联合麻醉与硬膜外麻醉对剖宫产患者血流动力学的影响。方法:选择我院2013年12月至2014年12月收治的80例行剖宫产手术产妇,按随机数字表法平均分为A组及B组各40例,A组产妇使用腰麻硬膜外联合麻醉(CSEA),B组产妇使用硬膜外麻醉(EA),比较两组产妇麻醉效果,血流动力学变化、新生儿Apgar评分及产妇不良反应发生情况。结果:A组产妇麻醉效果Ⅲ级比率85.0%,明显高于B组的22.5%(P0.05)。A组产妇心率(HR)在胎儿娩出10 min(T3)及手术结束(T4)时刻明显高于B组,收缩压(SBP)和舒张压(DBP)在胎儿娩出即刻(T2)明显高于B组,平均动脉压(MAP)在麻醉前(T1)和麻醉后(T4)明显高于B组,每博输出量(SV)在T2时刻明显低于B组,比较差异具有统计学意义(P0.05);两组产妇心输出量(CO)各时刻比较差异无统计学意义(P0.05)。A组新生儿在娩出1 min时Apgar评分明显高于B组(P0.05)。A组不良反应发生率为5.0%,B组产妇不良反应发生率为10.0%,两组比较差异无统计学意义(P0.05)。结论:对剖宫产手术患者使用CSEA麻醉效果明显优于EA,且患者血流动力学更为稳定,麻醉效果较完善,安全性高,可应作为剖宫产手术首选的麻醉方式。     

右美托咪定的临床麻醉应用进展

右美托咪定(dexmedetomidine,Dex)是高选择性α2-肾上腺素受体激动剂,具有镇静、镇痛、抑制交感神经活性、无呼吸抑制等药理性质。多项研究证实:围术期或ICUs住院期间给予患者右美托咪定,可以增加患者机械通气耐受力,减少机械通气时间,改善患者病情恢复,减少呼吸抑制,稳定血流动力学,减少麻醉剂用量及降低麻醉剂不良反应发生率,抑制应激反应,保护肺脏、神经功能、心脏功能,降低谵妄发生率,抗寒颤等作用特点。虽然右美托咪定存在心动过缓及低血压等不良反应,故应控制给药速度、剂量,合理用药在以便循环波动可控范围内。目前,右美托咪定可用于重症监护病房(ICUs)、全身麻醉、区域麻醉、小儿麻醉、日间手术及无痛检查等辅助用药。本文主要对右美托咪定的临床麻醉应用做以下介绍。     

Cholesterol level influences opioid signaling in cell models and analgesia in mice and humans

Cholesterol regulates the signaling of μ-opioid receptor in cell models, but it has not been demonstrated in mice or humans. Whether cholesterol regulates the signaling by mechanisms other than supporting the entirety of lipid raft microdomains is still unknown. By modulating cholesterol-enriched lipid raft microdomains and/or total cellular cholesterol contents in human embryonic kidney cells stably expressing μ-opioid receptor, we concluded that cholesterol stabilized opioid signaling both by supporting the lipid raft's entirety and by facilitating G protein coupling. Similar phenomena were observed in the primary rat hippocampal neurons. In addition, reducing the brain cholesterol level with simvastatin impaired the analgesic effect of opioids in mice, whereas the opioid analgesic effect was enhanced in mice fed a high-cholesterol diet. Furthermore, when the records of patients were analyzed, an inverse correlation between cholesterol levels and fentanyl doses used for anesthesia was identified, which suggested the mechanisms above could also be applicable to humans. Our results identified the interaction between opioids and cholesterol, which should be considered in clinics as a probable route for drug-drug interaction. Our studies also suggested that a low cholesterol level could lead to clinical issues, such as the observed impairment in opioid functions.     

寰枢关节尾向置管建立上胸段硬膜外阻滞大鼠模型

目的为持续上胸段硬膜外阻滞的试验研究提供稳定可靠的动物模型。方法以大鼠为研究对象,经寰枢关节尾向于硬膜外腔置入PE-10导管,采用特殊的固定和管理措施。4周后,大鼠硬膜外腔注入美蓝100μL/kg,尸检鉴定模型成功和药液的分布范围。结果置管后4周的成功率为65%,硬膜外腔的感染率为2.5%。结论本研究证实了经寰枢关节尾向置管建立持续上胸段硬膜外模型和特殊管理的可行性,并具有成功率高,稳定性好的特点。