急性心肌缺血期大鼠丘脑束旁核神经元5-HT1A受体mRNA表达的变化

目的：观察急性心肌缺血期大鼠丘脑柬旁核（parafascicular nucleus，Pf）神经元5-HT1A受体mRNA不同时点表达的变化，探讨5-HT1A受体在Pf痛觉整合和调制中的作用。方法：体重260～280g的健康成年雄性SD大鼠24只，随机分为4组，即非冠状动脉扎闭组（C组）、扎闭冠脉（coronary artery occlusion，CAO）lh组（CAO 1h组）、扎闭冠脉3h组（CAO 3h组）和扎闭冠脉6h组（CAO 6h组）。C片行原位杂交。杂交结果检测采用IDA-2000数码显微图像分析系统进行半定量分析。结果：CAO后1、3、6h大鼠Pf神经元5-HT1A受体mRNA的表达均较C组明显增强（P〈0．05），随缺血时间延长其表达有逐渐增加的趋势，在CAO后6h表达最强（P〈0、05）。结论：急性心肌缺血可诱发大鼠Pf神经元5-5-HT1A受体mRNA表达增强，5-HT1A受体参与急性心肌缺血伤害性刺激在Pf的调制。     

急性心肌缺血期大鼠丘脑束旁核神经元5-HT1A受体mRNA表达变化的研究

目的 观察急性心肌缺血期大鼠丘脑束旁核神经元5-HT1A受体mRNA不同时间点表达的变化，以探讨5-HT1A受体在丘脑束旁核痛觉整合和调制中的作用。方法 健康成年雄性SD大鼠24只，随机分为四组：对照组，即非冠状动脉扎闭（C组）组，扎闭冠状动脉（coronary artery occlusion，CAO）1h组（CAO1h组），扎闭冠状动脉3h组（CAO3h组）和扎闭冠状动脉6h组（CAO6h组）。对照组仅在开胸后冠状动脉左前降支下穿线不予结扎；CAO各组则扎闭冠状动脉左前降支。在预定的时点处死动物，取含有大鼠丘脑束旁核的脑片行原位杂交。杂交结果检测采用IDA-2000数码显微图像分析系统进行半定量分析。结果 CAO后1、3、6h大鼠丘脑束旁核神经元5-HT1A受体mRNA的表达均较对照组明显增强（P〈0．05），随缺血时间延长其表达有逐渐增加的趋势，在CAO后6h表达最强（P〈0．05）。结论 急性心肌缺血可诱发大鼠丘脑束旁核5-HT1A受体mRNA表达增强，5-HT1A 受体参与急性心肌缺血伤害性刺激在丘脑束旁核的调制。     

福尔马林致痛大鼠背根节内5-HT受体亚型mRNA的表达变化

目的:探讨外周5-HT受体亚型在外周伤害性感受中的作用.方法:用反转录PCR技术观察大鼠单侧足底皮下注射福尔马林致痛后背根节内5-HT1～7受体亚型mRNAs的表达变化.结果:在大鼠足底皮下注射福尔马林后1 h,注射侧腰段背根节内5-HT1A、5-HT1B、5-HT2A、5-HT3、5-HT4和5-HT7受体亚型mRNAs的表达水平显著升高,而5-HT1D、5-HT1F、5-HT2C、5-HT5A和5-HT6受体亚型mRNAs的表达在福尔马林致痛后无明显变化.在正常和福尔马林致痛大鼠的背根节内均未检测到5-HT1E、5-HT2B和5-HT5B受体亚型mRNAs的表达.结论:5-HT1A、5-HT1B、5-HT2A、5-HT3、5-HT4和5-HT7受体亚型可能参与了福尔马林诱导的炎性痛,且它们在外周伤害性信息的传递方面可能发挥不同的作用.     

阻断炎症局部5-HT2A受体对大鼠脊髓背角一氧化氮合酶表达的影响

目的:研究阻断局部炎症组织中的5-HT2A受体后,脊髓背角一氧化氮合酶的变化,以了解外周5-HT2A受体在慢性炎症维持中的作用。方法:给大鼠足掌皮下注射2%角叉菜胶(carrageenan),1h后注射5-HT2A受体拮抗剂酮舍林(ketanserin)20μg。24h于大鼠同一位点注射1%福尔马林(formalin)。25h灌流、取材,进行NADPH-d组织化学实验。结果:注射角叉菜胶和福尔马林后,双侧脊髓背角浅层的NADPH-d阳性神经元数目均增多,以同侧更为显著。给予酮舍林后明显抑制这种增加。外周阿片受体拮抗剂纳洛酮(naloxone methiodide)可使酮舍林对炎症引起NADPH-d阳性神经元的抑制作用完全消失。结论:阻断外周5-HT2A受体能抑制角叉菜胶和福尔马林炎性痛刺激引起脊髓背角神经元的活化,这种抑制作用可能是通过激活阿片镇痛机制,继而抑制一氧化氮信号通路实现的。     

8Hz次声对大鼠体重及胃十二指肠5-HT表达的影响

目的探讨 8Hz ,90dB、13 0dB次声对SD大鼠体重的影响及其可能机制。方法 3 0只雄性SD大鼠按体重随机分为对照组 ,8Hz、90dB及 8Hz、13 0dB组 3组。实验组分别暴露于 8Hz、90dB或 8Hz、13 0dB次声仓中 ,每日作用时间 2小时 ,共 42天。对照组每日置次声仓中 ,但不予次声作用 ,所有动物每 3天称体重 1次。另 75只随机分为对照组和 8Hz ,90dB、13 0dB的 7、14、2 1、2 8、3 5天组共 15组 ,每组 5只 ,按组别予以不同时间及强度的次声作用 ,对照组每日置次声仓中 ,但不予次声作用。最后一次从次声仓取出后立即取胃及十二指肠 (包括体重实验组各 5只 ) ,免疫组织化学染色显示其 5 羟色胺 (5 HT)含量。光学显微镜下计数胃窦及十二指肠 5 HT阳性细胞数。结果实验组大鼠体重增长均较对照组缓慢 (P =0 0 0 0 ) ,其中 13 0dB组对大鼠体重增长较 90dB组增长缓慢 (P =0 0 0 0 ) ;实验组动物胃窦及十二指肠 5 HT含量较对照组增多 ,以 90dB的 3 5天和 13 0dB的 2 8天明显 (P <0 0 1)。结论 8Hz、90dB及 8Hz、13 0dB次声对雄性SD大鼠体重的增长有抑制作用 ,其机制可能与胃及十二指肠 5 HT增多有关。     

三叉神经感觉神经元5-HT1D受体调节CGRP表达和释放的机制

偏头痛是最常见的原发性头痛之一,它严重影响着患者的身心健康。5-羟色胺1(5-hydroxytryptamine 1,5-HT1)受体激动剂已被有效用于偏头痛的治疗近三十年,关于其在偏头痛中的具体作用机制一直是大家研究的重点。近年来的研究进展显示,5-HT1受体激动剂治疗偏头痛的机制主要与减少三叉神经节表达和释放降钙素基因相关肽(calcitonin gene-related peptide,CGRP)的量有关,且该过程主要通过作用于三叉神经节感觉神经元中的5-HT1D受体,并通过电压门控性钙离子通道、有丝分裂原激活蛋白激酶磷酸酶-1、TRPV1等而发挥作用。本文就该过程的可能的具体机制做一综述。     

冰冻保存对机采血小板释放5-HT的影响

目的 观察冰冻保存对机采血小板释放5-HT 的影响.方法 常规以二甲基亚砜(DMSO)为冷冻保护剂、-80 ℃冰冻保存机采血小板30 d;采用全自动血细胞分析仪检测并比较冰冻保存前后血小板计数(PLT)、血小板平均体积(MPV)和血小板体积分布宽度(PDW);ELISA法检测冰冻前后及在阳离子没食子酸丙酯(C-PG)、凝血酶(thrombin,THB)、二磷酸腺苷(ADP)、胶原(Collagen)等不同PLT诱导剂激活作用下PLT释放5-HT的数量.结果 冰冻复苏后机采血小板计数变化不大(P>0.05),但MPV和PDW 均增加,血小板制品血浆5-HT含量也显著增高(P<0.01).在不同诱导剂作用下,新鲜血小板释放5-HT均高于冰冻保存的血小板,差异有显著性(P<0.01).结论 (1)机采血小板冰冻保存与解冻过程中,会引起血小板膜形态和生物活性改变.(2)冰冻保存后PLT对不同诱导剂的反应下降.     

针刺对抑郁症睡眠障碍大鼠行为学和海马5-羟色胺受体表达水平的影响

目的观察针刺治疗抑郁症睡眠障碍(SDD)的分子机制。方法将Open-Field法评分相近的36只Wistar大鼠随机分为3组:正常组、模型组和针刺组,每组12只。除正常组外,其余各组均接受18 d不同的应激。应激18 d后,再进行72 h快眼动睡眠剥夺造模。针刺组每天在应激前1 h进行针刺,连续21 d。21 d后,计算行为得分,取大鼠海马检测5-HT1A受体、5-HT2A受体mRNA水平。结果模型组大鼠自主活动较正常组明显减少(P<0.01);针刺组大鼠的自主活动较模型组明显增加(P<0.01)。与正常组相比,模型组大鼠海马5-HT1A受体mRNA表达明显下降,5-HT2A受体mRNA表达明显上升(均P<0.01);与模型组相比,针刺组大鼠海马5-HT1A受体mRNA表达上升、5-HT2A受体mRNA表达下降(P<0.05)。结论针刺可能通过调整5-HT受体间不平衡而发挥治疗SDD效应。     

心理治疗和针灸综合治疗失眠

目的观察失眠患者采用心理治疗和针灸综合治疗的临床效果。方法72例失眠患者分别采用心理和针灸综合治疗(治疗组)36例和单纯应用针灸治疗(对照组)36例,进行疗效比较。结果两组患者治疗1个月后,治疗组治愈15例,显效18例,有效2例,无效1例,总有效率97·2%;对照组治愈6例,显效12例,有效12例,无效6例,总有效率83·3%,两组间有显著性差异(P<0·05)。结论心理治疗和针灸综合治疗对失眠的治疗效果较单纯针灸治疗提高。     

强迫游泳大鼠海马组织5-羟色胺受体mRNA的表达

目的探讨强迫游泳大鼠海马组织中5-羟色胺（5-HT1A）受体激活物抑制因子-1（1mRNA）的表达。方法随机将雄性Wistar大鼠分为对照组、1d应激组、14d应激组和28d应激组,建立强迫游泳应激模型。用化学发光法测定血清皮质醇浓度,用逆转录聚合酶链式反应（RT-PCR）方法检测海马5-HT1A受体mRNA的变化。结果（1）对照组、1d应激组、14d应激组和28d应激组血清皮质醇浓度分别为（0．64±0．09）μg／dL、（1．14±0．19）μg／dL（1．98±0．40）μg／dL、（0．95±0．14）μg／dL。（2）强迫游泳大鼠海马5HT1A受体mRNA表达相对水平分剐为1．501±0．257、1．141±0．120、0．681±0．056,与对照组相比较,差异具有统计学意义（P〈0．05）。结论强迫游泳大鼠海马中5-HT1A受体mRNA表达降低。     

针灸治疗失眠的研究趋势： 基于CiteSpace的知识图谱分析

目的:分析并绘制针灸治疗失眠研究的科学知识图谱。方法:首先,检索CNKI中关于针灸治疗失眠的文章。其次,利用origin软件分析文献年度发文趋势。最后,通过CiteSpace软件分别分析绘制纳入文献的关键词共现网络、作者合作网络和机构合作网络。结果:截至2019年9月8日,从1999年到2019年,共确认1 165项针灸治疗失眠研究记录。年度出版物的数量逐渐增加并趋于稳定。关键词共现网络共有167个关键词被纳入,其中有27个关键词出现频次大于15。作者合作网络共有81位作者被纳入,其中发文量≥3篇的作者共计14位。机构合作网络中共有43所机构被纳入,其中有11所机构发文量≥3篇。结论:针灸治疗失眠症有效。     

Naratriptan has a selective inhibitory effect on trigeminovascular neurones at central 5-HT1A and 5-HT(1B/1D) receptors in the cat: implications for migraine therapy

The triptans are agonists at serotonin (5-HT)1B/1D receptors; however, they are also active at 5-HT1A and 5-HT1F receptors. We conducted this series of experiments to further elucidate the site of action of naratriptan using a well-established animal model of trigeminovascular stimulation. Following electrical stimulation of the superior sagittal sinus of the cat, single cell responses (n=83) were recorded in the trigeminal nucleus caudalis. Most cells (91%) also responded to electrical and mechanical stimulation of cutaneous or mucosal facial receptive fields. The microiontophoretic application of naratriptan resulted in a significant suppression of the response to sagittal sinus stimulation (response suppressed by 47 +/- 4%, P<0.001). The effect of naratriptan was significantly attenuated by application of either the 5-HT(1B/1D) receptor antagonist GR-127935 (P<0.001) or the 5-HT1A antagonist WAY-100635 (P<0.05). The response of single cells to receptive field stimulation was also suppressed by microiontophoretic application of naratriptan, but by only 20 +/- 3%. Intravenous administration of naratriptan resulted in a similar selective suppression of sagittal sinus vs. receptive field responses in trigeminal neurones. These results indicate that naratriptan has a central effect in the trigeminovascular system, selectively inhibiting afferent activity in craniovascular neurones, via both 5-HT(1B/1D) and 5-HT1A receptors.     

Mechanical, thermal and formalin-induced nociception is differentially altered in 5-HT1A-/-, 5-HT1B-/-, 5-HT2A-/-, 5-HT3A-/- and 5-HTT-/- knock-out male mice

Extensive studies in rodents suggest that serotonin (5-HT) modulates nociceptive responses through the stimulation of several receptor types. However, it remains to demonstrate that these receptors participate in the control of nociception under physiological conditions. Pain behaviors of mutants which do not express 5-HT_1A, 5-HT_1B, 5-HT_2A or 5-HT_3A receptors, or lacking the 5-HT transporter, compared to paired wild-type mice of the same genetic background, were examined using validated tests based on different sensory modalities. Mechanical (von Frey filaments, tail pressure, tail clip tests), thermal (radiant heat, 46 °C water bath, hot-plate test) and formalin-induced nociception were determined in 2- to 3-month-old males. 5-HT_1A knock-out mice differed from wild-types by higher thermal sensitivity (hot-plate test only), and 5-HT_1B knock-out mice by higher thermal and formalin sensitivity. Both 5-HT_2A and 5-HT_3A knock-out mice differed from wild-types by a dramatic decrease in the formalin-induced nociceptive responses for phase II (16–45 min after injection/inflammatory phase). In contrast, neither mechanical, thermal nor formalin-induced nociception differed between mutants lacking the 5-HT transporter and paired wild-type mice. Although differences in spontaneous locomotor activity in 5-HT_1B−/− (increase) and 5-HT_3A−/− (decrease) knock-out mice versus paired wild-types might have confounded differences in nociception, acute 5-HT receptor blockade by selective antagonists was found to replicate in wild-type mice the effects on pain behavior, but not on locomotor activity, of the respective gene knock-out in mutants. These results support the conclusion that the complex control of pain mechanisms by 5-HT, acting at multiple receptors, is physiologically relevant in mice.     

电针心包经穴对MCAO大鼠NR2A、NR2B表达的影响

目的:探讨电针心包经穴对MCAO大鼠不同时相点NR2A、NR2B表达的影响。方法:采用线栓法制备大鼠大脑中动脉栓塞(MCAO)模型,将其随机分为电针心包经组和模型组,再将每1组二次随机分为1d、3d、7d、14d、21d5个亚组。对电针心包经组进行电针治疗,用Western blot检测NR2A、NR2B的蛋白表达,用行为学评分评估大鼠处理前后运动功能障碍与恢复情况。结果:①行为学评分:同1时相点与处理前比较,模型组21d亚组处理后评分降低;电针心包经组3d、7d、14d、21d亚组处理后评分均明显降低,差异均有统计学意义。②NR2A、NR2B蛋白表达:同1时相点与模型组相比,电针心包经组1d、3d、7d亚组的NR2A、NR2B表达均明显降低,而14d、21d亚组的NR2A、NR2B表达均显著上升,差异均有统计学意义。结论:电针治疗脑梗死的作用机制可能与对不同时相点NR2A、NR2B的表达进行差异性调节,从而提高缺血耐受性,保护受损的神经细胞有关。     

Onset of effect of 5-HT1B/1D agonists: a model with pharmacokinetic validation

OBJECTIVE: To quantitate onset of effect of all formulations of sumatriptan, and to investigate whether this is related to rate, not extent, of drug absorption. METHODS: From published literature, for 4 formulations of sumatriptan and matching placebos, response rates were modeled using a simple logarithmic equation, with a being a parameter of curve convexity and B, a location parameter (equal to response rate at 2 hours [the standard regulatory parameter]). The average rate of drug absorption (A) was estimated by dividing the maximal drug concentration by the time needed to achieve it (Cmax/Tmax). Least mean square correlation was then performed between the therapeutic gains and therapeutic ratios of curve convexity and rate of drug absorption. RESULTS:-Models closely fitted observed response rates (2 hours or less). Curve convexity correlated with rate of drug absorption. Sumatriptan response rates (0 to 2 hours) for formulations correlated with rate, not extent, of drug absorption. The range of rates of onset of effect among different routes of administration was greater than that for tablets with 4-fold differences in dose size. CONCLUSION: Onset of effect is related to rate of absorption of sumatriptan. There is greater scope for improving onset of effect using an alternative route of administration than by increasing the oral dose.     

针刺对局部脑缺血大鼠大脑皮层基质金属蛋白酶-2表达的影响

目的：观察针刺对局部脑缺血大鼠大脑皮层基质金属蛋白-2（MMP-2）表达的影响。方法：Wistar大鼠24只,分为A、B、C3组各8只,A组大鼠不做任何处理,B、C组建立大鼠大脑中动脉阻塞模型（MCAO）,C组于造模结束30min后针刺大鼠肢体,5h后再针刺1次,以后每天1次,均20min。3组大鼠均采用半定量逆转录聚合酶链反应（RT-PCR）观察大鼠皮层MMP-2 mRNA的表达,免疫组化观察MMP-2蛋白的表达。结果：A组大鼠大脑皮层MMP-2 mRNA和MMP-2蛋白有少量表达,B组增高明显（P〈0.01）;与B组比较,C组MMP-2 mRNA及MMP-2蛋白表达也明显降低（P〈0.01,0.05）。结论：针刺可能通过降低MMP-2表达,减少脑水肿,保护脑组织。     

Decreased sensitivity of 5-HT1D receptors in chronic tension-type headache

OBJECTIVE: To assess the sensitivity of 5-HT1D receptors in chronic tension-type headache using sumatriptan as a pharmacological probe. BACKGROUND: Previous studies have suggested involvement of serotonergic systems in chronic tension-type headache (CTTH), but relevant experimental data are limited. Sumatriptan, a 5-HT1B/1D receptor agonist, stimulates the release of growth hormone (GH) and inhibits the release of ACTH, cortisol, and prolactin. These effects may be used to explore the function of serotonergic systems in vivo. METHODS: We measured GH, ACTH, cortisol and prolactin (PRL) plasma concentrations in 15 patients with chronic tension-type headache and in 18 healthy controls after subcutaneous administration of sumatriptan (6 mg) or placebo. RESULTS: Placebo administration had no effect on hormone concentrations. GH and PRL secretion after sumatriptan administration was significantly (P<0.01 and <0.05) altered in CTTH patients in comparison with controls. CONCLUSION: Our results suggest that cerebral serotonergic functions mediated by 5-HT1D receptors are altered in CTTH.