γ-氨基丁酸能神经元在丙泊酚缓解抑郁模型大鼠电休克后脑损伤中的作用

目的探讨γ-氨基丁酸(γ-aminobutyric acid,GABA)能神经元在丙泊酚缓解抑郁大鼠电休克(electroconvulsive shock,ECS)后学习记忆损伤中的作用。方法将慢性温和不可预见性应激(chronic unpredictable mild stress,CUMS)法建模成功的36只抑郁症模型大鼠随机分为丙泊酚+电休克组、电休克组和抑郁组,另设同批次未建模的12只健康大鼠为对照组。丙泊酚+电休克组用丙泊酚联合电休克治疗,电休克组行电休克治疗,抑郁组与对照组行伪电休克处理。治疗完毕行Morris水迷宫实验评估大鼠空间学习记忆能力;ELISA法检测海马GABA浓度;免疫组化法和Western-blot检测海马GABAARα5的蛋白表达。结果Morris水迷宫实验结果提示,电休克组逃避潜伏期最长,空间探索时间最短(P<0.05);电休克组和丙泊酚+电休克组比抑郁组逃避潜伏期延长,空间探索时间缩短(P<0.05);与对照组比较,其余各组逃避潜伏期缩短,空间探索时间延长(P<0.05)。蛋白表达方面,与对照组相比,抑郁组GABA含量下降,GABAARα5表达水平降低(P<0.05),电休克组和丙泊酚+电休克组GABA含量和GABAARα5蛋白表达升高(P<0.05);与电休克组相比,丙泊酚+电休克组GABA含量下降,GABAARα5蛋白表达升高(P<0.05)。结论丙泊酚在电休克过程中具有脑保护作用,其机制可能与上调海马GABA能神经系统相关递质和受体的表达有关。     

孕烯醇酮对老年SD大鼠海马区突触素蛋白1表达的影响

目的 观察孕烯醇酮(PREG)慢性干预对老年大鼠海马区突触素蛋白1(SYP1)表达的变化.方法 24月龄雄性SD大鼠40只,随机分为空白对照组、溶剂对照组、小剂量PREG(0.5 mg/kg)干预组、大剂量PR EG(2.0 mg/kg)干预组,隔日腹腔注射干预1个月,通过Western Blot技术和免疫组化技术检测分别检测各组大鼠海马区蛋白表达情况.结果 与对照组相比,免疫组化显示大剂量PREG干预组大鼠海马区SYP1表达明显增加,Western Blot定量检测发现大鼠海马区SYP1表达也显著升高(P＜0.05);而小剂量组SYP1表达无明显增加(P＞0.05).结论 大剂量PREG干预可以显著增加老年大鼠记忆相关的海马区SYP1表达,SYP1表达增加可能明显改善大鼠海马区突触结构可塑性与突触功能,进而有助于改善老年大鼠的学习记忆功能.     

戊四氮点燃癫痫大鼠空间学习记忆障碍及海马突触素表达减少的研究

目的:探讨戊四氮点燃癫痫对大鼠空间学习记忆的影响及可能的分子机制。方法:戊四氮(pentylenetet-razol,PTZ)点燃建立慢性癫痫(chronic epileptic,CEP)模型,Morris水迷宫进行行为学检测,western blot方法观察大鼠海马突触素(synaptophysin,P38)蛋白的表达变化。结果:水迷宫试验检测癫痫组大鼠空间学习记忆能力受损(P<0.05,P<0.01);western blot结果表明海马P38蛋白表达较对照组明显减少(P<0.05)。结论:戊四氮点燃癫痫大鼠伴有学习记忆功能减退,其海马P38蛋白的表达减少可能参与了空间学习记忆受损。     

无抽搐电休克治疗大鼠抑郁症与海马γ-氨基丁酸通路的关系

目的 观察抑郁大鼠无抽搐电休克治疗(MECT)后海马内谷氨酸脱羧酶-65(GAD65)的表达以及γ-氨基丁酸(GABA)含量的变化,并阻断γ-氨基丁酸A型受体(GABAA),探讨MECT治疗抑郁症与GABA通路的关系.方法 48只SD大鼠随机分为MECT治疗组(治疗组)、GABAA受体拈抗组(拮抗组)、抑郁模型对照组(模型组)、空白对照组(对照组),每组12只.前3组大鼠采用孤养加慢性轻度不可预见性应激建立抑郁模型,治疗组和拮抗组均隔天给予MECT处理6次,但后者在丙泊酚腹腔注射麻醉时同时注射GABAA受体特异性阻断剂荷包牡丹碱,余2组正常饲养.随后行open-field评分,每组随机抽取6只大鼠以免疫组织化学法检测海马GAD65蛋白的表达,其余6只以高效液相色谱法分析海马GABA含量.结果 ①open-field评分:电休克处理后,治疗组和拮抗组水平计分、垂直计分均高于模型组(P<0.05),拮抗组低于治疗组(P<0.05),提示电休克可有效缓解大鼠抑郁状态,阻断GABAA受体可减弱电休克疗效.②GAD65表达、GABA含最:模型组GAD65的表达量、GABA含量低于对照组(P<0.05),治疗组、拮抗组大鼠高于模型组(P<0.05),提示电休克可以上调GAD65表达,升高GABA含量.结论 无抽搐电休克可上调抑郁大鼠海马GAD65表达,升高GABA含量,改善抑郁症状,GABA通路可能部分参与了无抽搐电休克治疗抑郁症的机制.     

氯胺酮复合异丙酚麻醉对抑郁大鼠电休克后海马谷氨酸受体亚基1和亚基2的影响

目的评价小剂量氯胺酮复合异丙酚麻醉对抑郁大鼠电休克(electroconvulsive therapy,ECT)后海马谷氨酸受体亚基1(glutamate receptor subunit 1,Glu R1)及亚基2(glutamate receptor subunit 2,Glu R2)的影响。方法健康成年雄性SD大鼠32只,采用孤养与慢性轻度不可预见性应激(chronic unpredictable mild stress,CUMS)建立抑郁模型,建模成功后随机分为抑郁组(A组)、ECT组(B组)、ECT+异丙酚组(C组)和ECT+异丙酚+氯胺酮组(D组)4组,每组8只;另取8只正常大鼠作为对照组。对照组不做任何处理;A组腹腔注射生理盐水8 m L/kg后给予伪ECT处理;B、C、D组分别腹腔注射生理盐水8 m L/kg、异丙酚80 mg/kg、异丙酚80 mg/kg+氯胺酮10 mg/kg后行ECT处理,上述处理连续7 d。分别采用糖水偏好实验和Morris水迷宫实验评价大鼠抑郁状态和学习记忆功能,Western-blot及RT-PCR检测大鼠海马Glu R1和Glu R2及其m RNA表达。结果 ECT处理后,B、C、D组糖水偏好百分比变化均较A组和对照组明显,其中D组升高最为明显(均P0.05);B组逃避潜伏期延长且变化值与其他组均具有统计学差异,而D组逃避潜伏期缩短最为明显,其次为A组(均P0.05);B组空间探索时间缩短且变化值均大于其他组,D组空间探索时间延长最为明显(均P0.05)。ECT处理后,B、C、D组Glu R1表达较A组高,其中D组最高(均P0.05);Glu R1m RNA表达在组间无统计学差异B、C组Glu R2及其m RNA表达较其余组低,其中B组最低(均P0.05),A、D组和对照组间Glu R2及其m RNA差异无统计学意义(P0.05)。结论小剂量氯胺酮复合异丙酚麻醉在协同ECT抗抑郁效果的同时,能够更大程度地改善ECT后学习记忆功能,其机制可能与上调海马Glu R1和Glu R2表达相关。     

丙泊酚改善电休克后学习记忆与强直后增强研究

目的探讨强直后增强在丙泊酚改善抑郁大鼠电休克(electroconvulsive therapy,ECT)后学习记忆功能的作用。方法采用孤养与慢性轻度不可预见性应激(chronic unpredictable mild stress,CUMS)建立抑郁模型。选择成功建模的SD雄性大鼠72只,随机分为抑郁组(D组)、ECT组(DE组)、ECT复合丙泊酚组(DPE组)、丙泊酚组(DP组)4组,每组18只;另取18只正常大鼠作为对照组(C组)。C组不做任何处理,D、DE组给予生理盐水后分别行伪ECT和ECT处理;DPE、DP组给予丙泊酚后分别行ECT和伪ECT处理。观察大鼠的行为学变化,采用电生理技术记录强直后增强(post-tetanic potentiation,PTP)和基础场兴奋性突触后电位(field excitatory postsynaptic potential,f EPSP),检测海马谷氨酸浓度。结果 ECT处理后,DE和DPE组糖水偏好百分比均高于D组(P0.05);与DE组比较,DPE组逃避潜伏期缩短,空间探索时间延长(均P0.05)。ECT处理后,与C组比较,D、DE、DPE组PTP均降低且数值为(139%±3%,117%±4%,130%±6%),DE组PTP低于D组,DPE组PTP高于DE组(P0.05)。与D组比较,DE组和DPE组基础f EPSP均升高,DPE组基础f EPSP低于DE组(P0.05)。D、DE、DPE组谷氨酸浓度均低于C组,DE组较D组谷氨酸浓度升高,DPE组较DE组谷氨酸浓度降低(P0.05)。结论丙泊酚改善抑郁大鼠ECT处理后学习记忆功能的机制,可能与下调海马谷氨酸浓度,减轻PTP损伤有关。     

异丙酚联合电休克对抑郁大鼠海马卡配因Ⅰ-细胞周期依赖性蛋白激酶5通路的影响

目的观察异丙酚联合电休克对抑郁大鼠海马卡配因I(calpain I)-细胞周期依赖性蛋白激酶5(cyclin-dependent kinase 5,Cdk5)通路的影响。方法 SD大鼠50只随机分为抑郁模型组、异丙酚组、电休克组、异丙酚联合电休克组(简称联合组)和正常对照组各10只,前4组采用慢性轻度不可预见性应激建立抑郁模型。此后,抑郁模型组仅给予生理盐水,异丙酚组仅腹腔注射异丙酚,电休克组给予生理盐水加电刺激,联合组给予异丙酚加电刺激,对照组仅给予生理盐水,连续7d。采用open-field法评价抑郁状态,Morris水迷宫检测学习记忆功能,免疫组织化学法检测海马CA1区和CA3区calpain I的表达,western blot法和液闪法分别检测海马Cdk5的表达和活性,RT-PCR法检测calpain I及Cdk5 mRNA的表达。结果治疗后,电休克组和联合组的open-field评分高于抑郁模型组和异丙酚组,差异有统计学意义(P<0.05);电休克组的逃避潜伏期比抑郁模型组、异丙酚组和联合组延长而空间探索时间缩短(P<0.05);电休克组的calpain I和Cdk5的蛋白及mRNA表达与Cdk5的活性均高于抑郁模型组、异丙酚组(P<0.05),联合组的Cdk5蛋白及mRNA表达高于抑郁模型组和异丙酚组(P<0.05),而联合组较电休克组的表达减少[CA1区calpain I蛋白:(0.15±0.03)vs.(0.20±0.03),CA3区calpain I蛋白:(0.17±0.03)vs.(0.22±0.03),calpain I mRNA:(0.58±0.02)vs.(0.82±0.05),Cdk5蛋白:(0.76±0.05)vs.(1.13±0.05),Cdk5 mRNA:(0.46±0.01)vs.(0.63±0.03),Cdk5活性:(3272.92±137.57)vs.(5770.24±202.26)]。结论异丙酚减轻抑郁大鼠电休克处理后学习记忆损害,其机制可能与异丙酚降低了电休克处理后calpain I-Cdk5通路的表达有关。     

血管性痴呆大鼠海马突触素、发动蛋白Ⅰ的mRNA及蛋白表达变化

目的探讨血管性痴呆(VaD)大鼠海马突触素、发动蛋白Ⅰ的mRNA及蛋白表达变化。方法利用改良四血管法制备血管性痴呆大鼠模型。通过Morris水迷宫观察大鼠空间探索及学习记忆情况,采用Real-time及Western-blot法分别检测大鼠海马突触素、发动蛋白Ⅰ的mRNA与蛋白水平,并与假手术组进行比较。结果 VaD组大鼠各时间点平均逃避潜伏期及第1次穿越平台所用时间均显著长于假手术组(均P0.01),平台穿越次数明显减少(P0.05)。VaD组海马突触素及发动蛋白Ⅰ蛋白表达及mRNA表达显著低于假手术组(P0.05~0.01)。结论脑缺血引起大鼠海马组织突触素、发动蛋白Ⅰ表达降低,可能与VaD发病中学习记忆能力减退有关。     

无抽搐电休克治疗大鼠抑郁症的谷氨酸能机制研究

目的 观察抑郁大鼠电休克治疗后海马内谷氨酸含量以及N-甲基-D天门冬氨酸(NMDA)受体的表达,探讨电休克治疗抑郁症的谷氨酸能神经机制.方法 36只SD大鼠随机分为无抽搐电休克组(电休克组)、抑郁模型对照组(抑郁组)、对照组,每组12只.前两组采用孤养加慢性不可预见性应激建立抑郁模型,建模后电休克组在丙泊酚麻醉下行无抽搐电休克治疗,隔天1次共2周.检测各组海马谷氰酸含量和海马CA1区、CA3区NMDA受体2B亚单位(NMDA-NR2B)的表达.结果 ①电休克治疗后电休克组大鼠水平移动格数、垂直竖立次数和糖水消耗量都高于抑郁组(P＜0.01).②电休克组大鼠海马内谷氨酸含量低于抑郁组(P＜0.01),而抑郁组高于正常组(P＜0.01).③电休克组大鼠海马CA1区和CA3区NMDA-NR2B的表达量高于正常组(P＜0.05),而抑郁组低于正常组(P＜0.01).结论 无抽搐电休克治疗可抑制抑郁症模型大鼠海马内谷氨酸含量的升高并使NMDA-NR2B的表达量上调,这可能足其抗抑郁机制之一.     

小剂量氯胺酮保护抑郁大鼠电休克后学习记忆中Ⅱ组促代谢型谷氨酸受体的作用

目的探讨小剂量氯胺酮保护抑郁大鼠电休克(modified electroconvulsive shock,MECS)后学习记忆中Ⅱ组促代谢型谷氨酸受体(metabotropic glutamate receptors,m Glu R)的作用。方法 2~3月健康雄性Sprague Dawley(SD)大鼠,采用慢性轻度不可预见性应激(chronic unpredictable mild stress,CUMS)建立抑郁大鼠模型。选取30只建模成功的抑郁大鼠随机分为D组、M组、KM组,另取10只正常大鼠作为对照组(C组),腹腔注射给药,D组给予生理盐水后行伪电休克处理,M组和KM组分别给予丙泊酚及丙泊酚+氯胺酮(10 mg/kg)后行电休克处理,C组不做任何处理,行糖水偏好实验和水迷宫实验评价行为学变化,并检测海马m Glu R2和m Glu R3表达水平。另取12只抑郁大鼠进行电生理实验,将其随机分为对照组(P组)和Ⅱm Glu R阻断剂组(L组),制备海马脑片后分别予以正常人工脑脊液和含有Ⅱm Glu R阻断剂的人工脑脊液灌流,应用电生理技术记录海马Schaffer侧枝-CA1神经通路(SC-CA1)长时程增强(long-term potentiation,LTP)。结果实验处理后,与D组相比,M组和KM组糖水偏好百分比升高(P0.01),M组逃避潜伏期延长(P0.01),目标象限探索时间缩短(P0.01),KM组逃避潜伏期缩短,目标象限探索时间延长(P0.01)。与C组相比,D组、M组、KM组m Glu R2、m Glu R3蛋白表达水平降低(P0.05);与M组相比,D组、KM组蛋白表达升高(P0.05);D组与KM组之间差异无统计学意义(P0.05)。P组海马SC-CA1神经通路LTP高于L组(P0.05)。结论小剂量氯胺酮可改善抑郁大鼠电休克后学习记忆功能损害,其机制可能与上调海马m Glu R2和m Glu R3表达有关。     

Maintenance Electroconvulsive Therapy and Seizure Duration

A retrospective study was conducted of 14 affectively ill patients who were treated with long-term unilateral maintenance electroconvulsive therapy (MECT). The patients had received an inpatient course of ECT before being referred for MECT. The average age was 57 +/- 16 years (range 30-91). The average interval between inpatient ECT was 2.4 +/- 0.9 days, in contrast to the interval between MECT, which was 12.1 +/- 11.3 days. The average time to start MECT after inpatient ECT was 16.2 +/- 16.2 days. The average duration of MECT was 81 +/- 104 days (maximum 571). Patients' affective symptoms continued to improve during the course of MECT based on Carroll Depression Ratings. Adjustment of the electrical dose and caffeine augmentation were used to keep the seizure durations >30 s by electroencephalograph (EEG) monitoring. Over time, most treatments were administered using the maximal charge provided by the Mecta SR-1. Despite considerable time intervals between MECT treatments, seizure durations did not increase. Additionally, high stimulus charge and frequently administered caffeine were used to maintain seizure length. The apparent anticonvulsant effect of ECT was not lost over the time span of MECT. This has clinical implications if the anticonvulsant effects of ECT contribute to determining the clinical response.     

无抽搐电休克与传统电休克治疗精神分裂症急性兴奋临床观察

目的 观察无抽搐电休克(MECT)与传统电休克(ECT)治疗精神分裂症患者急性兴奋的疗效和安全性.方法 将急性精神分裂症兴奋患者71例随机分为MECT组(治疗组)和ECT组(对照组),共治疗5次,采用阳性和阴性症状量表(PANSS)中兴奋因子(PANSS-EC)的变化评定临床疗效,副反应量表(TESS)评定不良反应,治疗前及治疗后分别评定血、尿、生化常规及心电图、血清CPK.结果 MECT组的PASS-EC总分明显降低,PASS-EC减分率(71±27)%,临床总有效率52.7%;ECT组PANSS-EC减分率(67±24)%,临床总有效率45.7%,2组间差异均无统计学意义(P均＞0.05).MECT组总的不良反应发生率41.7%,ECT组为54.3%,2组差异无统计学意义(P＞0.05).ECT组的头晕、头痛、肌肉酸痛发生率明显高于MECT组,差异有统计学意义(P＜0.05或＜0.01).结论 MECT治疗精神分裂症急性兴奋疗效肯定,安全性高.     

Anesthesia and electroconvulsive therapy: a retrospective study comparing etomidate and propofol

BACKGROUND: The choice of anesthetic can influence the efficacy of electroconvulsive therapy (ECT). In the UK, propofol is a popular induction agent for ECT, but is associated with higher stimulus charge, shorter seizures, and known to affect seizure threshold. Etomidate is an alternative induction agent but there are concerns over its adverse events and safety. OBJECTIVES: We examined the differences between propofol and etomidate in the real life situation of an ECT clinic by assessing their effect on (i) length of course of ECT (ie, number of treatments required to remission), (ii) adverse effects of each induction agent, (iii) the number of 'missed seizures,' and (iv) stimulus dose (charge in mC), which relates to seizure threshold. METHOD: Using a retrospective naturalistic study design, 94 patients were identified over a 36-month period in our ECT clinic, of which, 65 met the inclusion criteria. Of these, 36 had received etomidate and 29 had received propofol as induction agents throughout their course of ECT. RESULTS: Patients who received propofol had a significantly longer course of ECT, higher seizure thresholds, and increased amounts of electrical charge (mC) over their course. There were no significant differences in adverse events with either of the induction agents. CONCLUSIONS: When used for acute courses of ECT, propofol and etomidate are equally well tolerated as induction agents. Patients who received propofol had longer acute courses of ECT and, consequently, longer and costlier inpatient stays. Etomidate could be a better alternative induction agent in ECT.     

A seasonal schedule for maintenance ECT.

The case of a patient with bipolar disorder is presented to illustrate that past clinical course may suggest flexible scheduling strategies for maintenance ECT (MECT), which will allow some patients to be successfully treated with the fewest number of ECT. For 7 years prior to MECT, manic episodes regularly occurred during early summer and late autumn/early winter. ECT rapidly aborted the mania in the two episodes prior to referral for MECT. Given the rhythmicity of his manic episodes, MECT was begun by giving four outpatient ECT during the two at-risk periods each year to both abort and prevent affective episodes and to stop cycling. No breakthrough hypomania occurred by the third such period, and the ECT was reduced to three ECT for the following period and two for the next. The patient had no significant affective episodes or hospitalizations during the 3 years of MECT. He continued maintenance lithium carbonate between ECT. This treatment strategy has allowed the patient to maintain stability in his employment and personal life.     

Maintenance ECT in Parkinson's disease

Summary. Electroconvulsive therapy (ECT) has an anti-Parkinsonian effect. In two cases repeated single ECT, i.e. maintenance ECT (MECT), caused different, hitherto unreported positive effects. One patient had either severe mental side effects from higher L-dopa doses or intolerable parkinsonian symptoms on lower doses. MECT entailed a marked improvement in parkinsonian symptoms without mental side effects. Another patient with depression as well as Parkinson's disease who showed a slight improvement of motor symptoms after a series of ECT presented further anti-parkinsonian effects on MECT. Received November 12, 1998; accepted April 13, 1999     

Electroconvulsive therapy pre-treatment with low dose propofol: Comparison with unmodified treatment

BackgroundWhilst electroconvulsive therapy (ECT) is routinely administered under anesthesia in developed nations, in many developing countries, ECT is still administered unmodified. This practice has attracted considerable scrutiny with calls to ban unmodified ECT. However, there are no affordable alternatives for many poor, acutely ill psychiatric patients. We evaluated whether administration of intravenous propofol 0.5 mg/kg for sedation by the ECT psychiatrist just prior to otherwise unmodified treatment improved acceptance of and reduced anxiety surrounding the treatment.MethodWe conducted an open label trial at The King George's Medical University in Lucknow, India. Forty-nine patients received propofol pre-treatment and 50 patients received unmodified treatment as usual.ResultsSocio-demographic profiles, diagnoses and clinical responses were comparable. Patients who received propofol experienced less anxiety monitored by the State-Trait Anxiety Inventory just prior to ECT (p < 0.001), and had a more favorable attitude towards treatment assessed by an established questionnaire (Freeman and Kendell, 1980). Propofol patients were less likely to experience post-ictal delirium monitored by the CAM-ICU (p = 0.015) and had fewer cognitive side-effects on the MMSE (p = 0.004). There were no adverse events associated with propofol administration.ConclusionWhilst unmodified ECT should never be used when modified ECT under anesthesia is available, we have found low dose propofol can be safely administered by the ECT psychiatrist to sedate patients pre-treatment who would otherwise receive completely unmodified treatment. The intervention was associated with reduced anxiety and a more positive attitude towards ECT, without compromising efficacy. A randomized double blind controlled study is necessary to confirm these benefits.     

Electroconvulsive therapy as an alternative treatment for obese patients with mood disorders

With the increased use of atypical antipsychotic medication in the treatment of mood disorders, patients are increasingly experiencing side effects, such as obesity, insulin resistance, and the metabolic syndrome, which, in turn, increases the risk of developing cardiovascular disease, type 2 diabetes, and hypertension. Maintenance electroconvulsive therapy (MECT) can be used as a prophylaxis for the recurrence of mood episodes for treatment-resistant patients. There are no reports of metabolic syndromes associated with ECT. We reviewed the charts of 10 patients who have received MECT at our institution over the last 10-year period. Five of 10 patients were obese pre-ECT, all of whom had a significant weight loss after ECT. Patients whose weights were normal pre-ECT, did not experience weight loss. Our finding suggests that ECT is a viable alternative for overweight patients with mood disorders who do not respond to mood stabilizers or cannot tolerate side effects.     

A naturalistic review of maintenance ECT at a university setting

This is a naturalistic review of maintenance electroconvulsive therapy (MECT) during the first 4 1/2 years of a university ECT service. A total of 56 patients, ages 30-84, received MECT. Patients could be classified under five different clinical groups: major depression; bipolar disorder; combined depression and axis 2 disorder; Parkinson's disease plus depression; and schizophrenia. Effectiveness in the different groups and issues related to partial improvement or treatment failure are discussed.     

瑞芬太尼与异丙酚在无抽搐电休克治疗中的联合应用

目的：研究单次静注瑞芬太尼与异丙酚对无抽搐电休克治疗（MECT）患者的血流动力学的影响。方法：抑郁症患者60例，随机分为瑞芬太尼合用异丙酚组和单用异丙酚组。每组30例，麻醉诱导采用静注长托宁1．0mg，异丙酚1．5mg／kg后，两组分别予生理盐水或瑞芬太尼1μg／kg。结果：单用组治疗后各项参数明显升高，持续3min，合用组治疗后1min各指标与麻醉前值比较明显上升，但治疗后3min即恢复。结论：瑞芬太尼与异丙酚联合运用，可有效抑制MECT时的血流动力学反应。