Melanocortin 3,5 receptors immunohistochemical expression in colonic mucosa of inflammatory bowel disease patients:A matter of disease activity?

BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin family.However,data regarding their role in inflammatory bowel diseases(IBD)are currently unavailable.AIM This study aims to ascertain their expression profiles in the colonic mucosa of Crohn’s disease(CD)and ulcerative colitis(UC),aligning them with IBD disease endoscopic and histologic activity.METHODS Colonic mucosal biopsies from CD/UC patients were sampled,and immunohisto-chemical analyses were conducted to evaluate the expression of MC3R and MC5R.Colonic sampling was performed on both traits with endoscopic scores(Mayo endoscopic score and CD endoscopic index of severity)consistent with inflamed mucosa and not consistent with disease activity(i.e.,normal appearing mucosa).RESULTS In both CD and UC inflamed mucosa,MC3R(CD:+7.7 fold vs normal mucosa,P<0.01;UC:+12 fold vs normal mucosa,P<0.01)and MC5R(CD:+5.5 fold vs normal mucosa,P<0.01;UC:+8.1 fold vs normal mucosa,P<0.01)were significantly more expressed compared to normal mucosa.CONCLUSION MC3R and MC5R are expressed in the colon of IBD patients.Furthermore,expression may differ according to disease endoscopic activity,with a higher degree of expression in the traits affected by disease activity in both CD and UC,suggesting a potential use of these receptors in IBD pharmacology.

Inhibition of 5-HT_3 Receptors-activated Currents by Cannabinoids in Rat Trigeminal Ganglion Neurons

This study investigated the modulatory effect of synthetic cannabinoids WIN55,212-2 on 5-HT3 receptor-activated currents (I5-HT3) in cultured rat trigeminal ganglion (TG) neurons using whole-cell patch clamp technique. The results showed that: (1) The majority of examined neurons (78.70%) were sensitive to 5-HT (3–300 μmol/L). 5-HT induced inward currents in a concentration-dependent manner and the currents were blocked by ICS 205-930 (1 μmol/L), a selective antagonist of the 5-HT3 receptor; (2) Pre-application of WIN55,212-2 (0.01–1 μmol/L) significantly inhibited I5-HT3 reversibly in concentration-dependent and voltage-independent manners. The concentra-tion-response curve of 5-HT3 receptor was shifted downward by WIN55,212-2 without any change of the threshold value. The EC50 values of two curves were very close (17.5±4.5) mmol/L vs. (15.2±4.5) mmol/L and WIN55,212-2 decreased the maximal amplitude of I5-HT3 by (48.65±4.15)%; (3) Neither AM281, a selective CB1 receptor antagonist, nor AM630, a selective CB2 receptor antagonist reversed the inhibition of I5-HT3 by WIN55,212-2; (4) When WIN55,212-2 was given from 15 to 120 s before 5-HT application, inhibitory effect was gradually increased and the maximal inhibition took place at 90 s, and the inhibition remained at the same level after 90 s. We are led to concluded that-WIN55,212-2 inhibited I5-HT3 significantly and neither CB1 receptor antagonist nor CB2 receptor antagonist could reverse the inhibition of I5-HT3 by WIN55,212-2. Moreover, WIN55,212-2 is not an open channel blocker (OCB) of 5-HT3 receptor. WIN55,212-2 significantly inhibited 5-HT-activated currents in a non-competitive manner. The inhibition of I5-HT3 by WIN55,212-2 is probably new one of peripheral analgesic mechanisms of WIN55,212-2, but the mechanism by which WIN55,212-2 inhibits I5-HT3 warrants further investigation.

Augmentative effect of tetrandrine on pentobarbital hypnosis mediated by 5-HT_(1A) and 5-HT_(2A/2C) receptors in mice

It has been reported that augmentative effect of tetrandrine on pentobarbital hypnosis in mice may be related to serotonergic system. The present study was undertaken to investigate the interaction of tetrandrine and different 5-HT receptors on pentobarbital-induced sleep by using the loss-of-righting reflex method. The results showed that augmentative effect of tetrandrine on pentobarbital hypnosis in mice were potentiated by the p-MPPI （5-HT1A receptor antagonist） （1 mg/kg, i.p.） and ketanserin （5-HT2A/2C receptor antagonist） （1.5 mg/kg, i.p.）, respectively. Pretreatment with either 8-OH-DPAT （5-HT1A receptor agonist） （0.1 mg/kg, s.c.） or DOI （5-HT2A/2C receptor agonist） （0.2 mg/kg, i.p.） significantly decreased pentobarbital-induced sleep time, and tetrandrine （60 mg/kg, i.g.） significantly reversed this effect. These results suggest that both the 5-HTLA and 5-HT2A/2C subfamily may be involved in the potentiating mechanism of tetrandrine＇s effects on pantobarbital hypnosis.

探讨5-HT3受体基因多态性与妇科腹腔镜手术患者术后恶心呕吐的关联

探讨5-HT3受体基因多态性与妇科腹腔镜手术患者术后恶心呕吐(PONV)的相关性。方法 选取我院2022年1月至2023年1月收治的123例腹腔镜下接受妇科手术的患者为研究对象,根据其24小时内是否发生PONV分为PONV组(n=63)和非PONV组(n=60),采取DNA直接测序、聚合酶链式反应检测HTR3A、HTR3B基因中的rs1176713、rs33940208、rs1985242、rs10160548、rs3758987、rs3831455等6个单核苷酸多态性位点在两组患者中的等位基因和基因型分布,分析相关遗传变异与PONV易感性的相关性,并通过Logistic回归分析进行相关性判断。结果 在本研究选择的123例患者中,共有63例(51.2%)发生PONV。单因素分析结果提示镇痛药使用剂量越大(P<0.05)或者术前具有晕动症病史(P<0.05)均可能导致患者术后发生恶心呕吐。对5-HT3受体基因多态性与术后恶心呕吐的关系分析结果提示,HTR3A基因的多态性位点rs1176713基因型分布频率与术后恶心呕吐具有明显的相关性(P<0.05)。二元logistic回归分析显示镇痛药使用(ug)和晕动症史(有无)为导致术后24小时恶心呕吐发生的独立危险因素(P<0.05)。结论 5-HTR3A基因rs1176713位点的遗传多态性与全麻下妇科腹腔镜患者术后恶心呕吐存在相关性,其杂合突变基因型GA为PONV的致病危险因素,纯合野生基因型AA为其保护因素。

Support vector classification for SAR of 5-HT3 receptor antagonists

In this work, support vector classification （SVC） algorithm was used to build structure-activity relationship （SAR） model of the 5-hydroxytryptamine type 3 （5-HT3 ） receptor antagonists with 26 compounds. In a benchmark test, SVC was compared with several techniques of machine learning currently used in the field. The prediction performance of the model was discussed on the basis of the leave-one-out cross-validation. The results show that the accuracy of prediction of SVC model was higher than those of back propagation artificial neural network （BP ANN）, K-nearest neighbor （KNN） and Fisher methods.

The 5-HT2c receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation

It has been postulated that the persistent short intravaginal ejaculation latency time （IELT） of men with lifelong premature ejaculation （LPE） is related to 5-hydroxytryptamine （HT）2c receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2c receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2c receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2c receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were.investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2c receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes （Cys/Cys） is significantly lower （22.6s; 95% CI 18.3-27.8s） than in male homozygous mutants （Ser/Ser） （40.4s; 95% CI 20.3-80.4s） （P = 0.03）. It is concluded that Cys23Ser 5-HT2c receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.

Roles of 5-HT2 receptors in effects of DOM,ketamine and methamphetamine on prepulse inhibition in Sprague Dawley rats

OBJECTIVE Prepulse inhibition(PPI)of the acoustic startle response provides a measure of sensorimotor gating system mecha⁃nisms,which is known to be impaired in schizo⁃phrenia patients.We assessed the effects of the 5-HT2A/2C receptor agonist(±)2,5-dimethoxy-4-methylamphetamine(DOM),the NMDA receptor antagonist ketamine,the dopamine receptor ago⁃nist methamphetamine(Meth)on PPI and the startle magnitude in SD rats.METHODS AND RESULTS Systemic administration of the three compounds all dose-dependently reduced PPI.However,as far as startle magnitude,only DOM at the doses of 3 mg·kg-1 reduced that,while both ketamine and Meth did not change the startle magnitudes.Furthermore,to determine whether 5-HT2A receptor mediate this effect,the non-spe⁃cific 5-HT2 receptor antagonist cyproheptadine,specific 5-HT2A receptor antagonist ketanserin and specific 5-HT2C receptor antagonist SB242084 were tested.Cyproheptadine,ketan⁃serin and SB242084 did not alter startle ampli⁃tude by themselves in SD rats and only ketanserin slightly increased PPI at higher dose(3 mg·kg-1).PPI impairment induced by DOM was restored by pretreatment of cyproheptadine(1 mg·kg-1)and ketanserin(1 mg·kg-1),while not by pretreat⁃ment of SB242084(1 mg·kg-1).Damage of PPI induced by ketamine and Meth was not reversed by cyproheptadine(1 and 5 mg·kg-1).CONCLU⁃SION The receptor mechanisms underlying the disruption of PPI caused by DOM,ketamine and Meth were different from each other,at least 5-HT2A receptor was not the junction receptor for which the three chemicals acted.

Effects of Activation and Blockade of Serotonin 5-HT1A Receptors on the Immune Response in Rats Selected for Different Levels of Aggressiveness

The present study examines the effects of serotonin (5-HT) 1A receptor ligands on humoral im-mune response in two rat lines selected for over 75 generations for the enhancement or elimination of aggression. Activation of presynaptic 5-HT1A receptors with a low dose of the selective 5-HT1A receptor agonist 8-OH-DPAT (0.1 mg/kg) or the blockade of postsynaptic 5-HT1A receptors with the antagonist WAY-100635 (1.0 mg/kg) did not affect the numbers of IgM-antibody forming cells (IgM-AFC) in the spleen of highly aggressive rats, which were characterized by higher immune responsiveness compared to nonaggressive line. On the other hand, the same doses of 8-OH-DPAT and WAY-100635, as well as a higher dose of 8-OH-DPAT (1.0 mg/kg), which is known to activate postsynaptic 5-HT1A receptors, produce immunostimulation in nonaggressive rats. However, only the highest dose of 8-OH-DPAT (5.0 mg/kg) was able to cause immunosuppression in nonaggressive rats that was mainly dependent on stimulation of postsynaptic 5-HT1A receptors. In contrast to nonaggressive rats, the dose of 1.0 mg/kg 8-OH-DPAT was sufficient to produce a decrease in the numbers of IgM-AFC in highly aggressive rats. Thus, pharmacological activation of pre- and postsynaptic 5-HT1A receptors, as well as the blockade of postsynaptic 5-HT1A receptors, produced different effects on the immune response in two lines of rats selected for high level of aggression or its absence. These data may have implications for more efficient treatments of a number of mental disorders associated with abnormal aggression.

Role of 5-HT2A Receptors in Immunomodulation in Animal Models of Aggressive Behavior

Serotonin 5-HT2A receptors are playing an important role in the pathophysiology of aggressive behaviors and in the control of immune function. In the present study, we analyzed the effects of activation and blockade of 5-HT2A receptors with selective ligands on the immune response formation in animals with aggressive behaviors induced by genetic factors (rats selected for the increased aggressiveness toward human) or by chronic social stress (mice of the CBA/Lac strain engaged in 10 days of social confrontations). Activation of 5-HT2A receptors with DOI at 1.0 mg/kg reduced the immune response level both in aggressive rats and mice compared to the corresponding vehicle-treated groups, while DOI administration did not alter the immune reaction in nonaggressive animals. The blockade of 5-HT2A receptors with ketanserin at 1.0 mg/kg resulted in immunostimulation both in mice of the CBA strain not subjected to social stress (the controls) and in nonaggressive rats selected for elimination of aggressiveness. On the other hand, its administration to CBA mice demonstrating offensive aggression enhanced the immune reaction, while the same dose of ketanserin did not modify the immune response level in rats with genetic predisposition to the increased defensive aggression. Thus, our data suggest that the role of 5-HT2A receptors in immunomodulation depends on the specific type of aggression that may be taking into account in the treatment of some neuropsychiatric disorders with the antipsychotic drugs and antidepressants targeting 5-HT2A receptors.

重复使用5-HT3受体拮抗剂预防多日化疗相关性恶心呕吐的疗效和安全性分析

目的:探讨重复使用第一代5-HT3受体拮抗剂(5-HT3RA)托烷司琼与第二代5-HT3RA帕洛诺司琼预防多日高度催吐风险化疗所致恶心和呕吐(chemotherapy-induced nausea and vomiting,CINV)的疗效和安全性。方法:在接受含有高度催吐风险药物连续多日化疗的患者中,采用随机、交叉自身对照的方法分组,A方案组为:在第1周期化疗中,帕洛诺司琼0.25 mg,静脉滴注,d1、d3(必要时d5)。地塞米松(DXM)10 mg,静脉滴注,d1;5 mg,静脉滴注,d2~d5。第2周期为托烷司琼5 mg,静脉滴注,d1~d3(必要时d4、d5);DXM用法同前。B方案组的止吐方案为第1周期使用托烷司琼,第2周期使用帕洛诺司琼(剂量、用法均同A方案组)。将A方案组第1个周期和B方案组第2个周期的患者归为帕洛诺司琼组,A方案第2个周期和B方案组第1个周期的患者归为托烷司琼组,比较帕洛诺司琼与托烷司琼预防CINV的疗效和不良反应。结果:共计入组91例患者。在d3至d5,帕洛诺司琼组每天恶心发生率分别为28.6%、30.8%和24.2%,托烷司琼组分别为42.8%、47.3%和39.6%,差异均有统计学意义(均P<0.05);在d4至d6,帕洛诺司琼组每天呕吐发生率分别为28.6%、18.7%和5.5%,托烷司琼组则为42.9%、34.1%和14.3%,差异均有统计学意义(均P<0.05);按时间段分析,帕洛诺司琼组在d4~5、d6~7和全程(d1~7)恶心和呕吐发生率均显著低于托烷司琼组(均P<0.05)。帕洛诺司琼组全程(d1~7)解救药使用率为13.2%,低于托烷司琼组的24.2%,但差异无统计学意义(P=0.057)。帕洛诺司琼组与托烷司琼组的止吐药物相关性不良反应发生率的差异均无统计学意义(均P>0.05)。结论:重复使用帕洛诺司琼预防持续多日高度催吐风险化疗相关的延迟性恶心呕吐的疗效优于托烷司琼,两者的安全性良好。

5-HT_2和5-HT_3受体在外周初级感觉神经末梢痛反应和痛调制中的相互作用

目的:探讨5-HT2和5-HT3受体亚型在5-HT引起外周痛反应和痛调制中的相互作用及其机制;方法:在大鼠三叉神经节神经元标本上应用全细胞膜片钳技术记录5-羟色胺激活电流(I5-HT),并结合痛行为实验进行观察。结果:在大多数受检细胞(54/88,61.4%)特别是中、小型细胞外加5-HT可引起一快去敏感的内向电流,此内向电流能被5-HT3受体特异性激动剂2-甲基-5-羟色胺所模拟,被5-HT3受体拮抗剂ICS250-930可逆性阻断,而5-HT2受体激动剂α-甲基-5-羟色胺则有明显增强I5-HT的作用,5-HT1受体激动剂R-(+)-UH301无明显反应。在进一步的整体清醒动物的行为学试验中我们观察到,大鼠后肢掌底皮下注射5-HT(10-5,10-4和10-3mol/L)引起浓度依赖性的痛行为反应,而用5-HT2和5-HT3受体特异性拮抗剂Cyproheptadine和ICS250-930分别阻断相应受体亚型后,5-HT引起的痛行为反应的强度序列为:5-HT>5-HT+ICS>5-HT+Cyp。结论:本文结果提示:5-HT所引起的痛反应中,在初级感觉神经元水平5-HT3受体可能仅起着启始作用,而5-HT2受体则在伤害性信息的维持和调制过程中发挥更大的作用。

电针对腹泻型肠易激综合征患者结肠黏膜5-HT、5-HT3R表达的影响

目的:观察电针对腹泻型肠易激综合征患者结肠黏膜5-HT、5-HT3R表达的影响,探讨其作用机制。方法:分别选取给予电针治疗(选取中脘、天枢、气海等穴,针刺后加电刺激,4周为1个疗程)16例和西药治疗(口服地衣芽孢杆菌和黛力新片)15例的腹泻型IBS患者治疗前后的乙状结肠黏膜组织,采用免疫组化法观察两组患者结肠黏膜5-HT、5-HT3R表达情况。结果:电针组和西药组两组患者治疗前结肠黏膜5-HT、5-HT3R阳性面积和光密度(OD)表达均较正常人有显著性升高(P<0.01,P<0.01);两组患者治疗后均较治疗前有显著性降低(P<0.01,P<0.01),电针组治疗后结肠黏膜5-HT、5-HT3R阳性面积表达则较西药组明显降低,两组间比较差异有统计学意义(P<0.05,P<0.05)。结论:电针可能通过显著降低腹泻型IBS患者结肠黏膜5-HT、5-HT3R表达,进而减弱神经介导的胃肠道运动与分泌,提高内脏痛阈,消除肠道过敏,由此改善胃肠道运动功能状态和内脏高敏感性而达到其治疗之目的。

大鼠海马内5-HT_3受体参与神经免疫调制

目的 :探讨大鼠海马不同部位 5 HT3受体对免疫的调制作用。方法 :通过小鼠腹腔和大鼠侧脑室和海马不同结构内注射 5 HT3受体激动剂 1 phenylbiguanide(PBG)后不同时间 ,用3H TdR掺入法观察对ConA、LPS刺激的脾T和B淋巴细胞增殖效应的影响 ,并观察选择性 5 HT3受体拮抗剂托烷司琼 (tropisetron ,Trop)对PBG作用的影响。结果 :小鼠腹腔注射、大鼠侧脑室和双侧腹侧海马注射 5 HT3受体激动剂PBG后可增强ConA、LPS刺激的脾T和B淋巴细胞增殖效应 ;双侧背侧海马内注射PBG后抑制ConA刺激的脾T淋巴细胞增殖效应 ,而不影响LPS刺激的B淋巴细胞增殖效应 ;5 HT3受体激动剂对脾细胞增殖效应的影响可被同时给予的托烷司琼阻断。结论 :提示大鼠海马 5

生姜对5-HT_3受体介导的豚鼠离体回肠收缩的影响

目的观察生姜及其主要辛辣成分对豚鼠离体肠管收缩的影响,从5-HT_3受体(5-HT_3receptor,5-HT_3R)角度探讨生姜的止吐机制。方法采用豚鼠离体回肠为实验材料,利用离体浴槽,在低、中、高3个浓度的姜汁(50,100,200μL)、6-姜酚(3×10^(-5),1×10^(-5),3×10^(-6) mol·L^(-1))、6-姜烯酚(3×10^(-5),1×10^(-5),3×10^(-6) mol·L^(-1))存在和不存在情况下,分别建立5-羟色胺(5-hydroxytryptamine,5-HT)和选择性5-HT_3R激动剂二甲基五羟色胺(2-Methyl-5-hydroxytryptamine,2-me-5-HT)的量效曲线,观察对肠管收缩和量效曲线的影响。结果姜汁、6-姜酚、6-姜烯酚均能剂量依赖性地抑制离体肠管自主收缩,使平均张力降低(与蒸馏水组相比,P<0.01,P<0.001);均能剂量依赖性地抑制5-HT和2-me-5-HT激发的离体肠管收缩增强,降低其平均张力(P<0.05,P<0.01,P<0.001);均可剂量依赖性地使5-HT和2-me-5-HT的最大效应降低(P<0.05,P<0.001);与阳性药昂丹司琼(3×10^(-7) mol·L^(-1))存在时比较,均可使5-HT和2-me-5-HT的最大效应显著降低(P<0.05,P<0.01,P<0.001)。姜汁、6-姜酚、6-姜烯酚均可使5-HT和2-me-5-HT的量效曲线非平行右移,并使最大效应显著降低。结论生姜及其主要辛辣成分可以非竞争性阻断5-HT_3R,这可能是生姜止吐作用的重要机制。

大鼠脊髓内5-HT_(2C),5-HT_3,5-HT_6和5-HT_7受体亚型mRNAs的表达(英文)

目的 :观察 5 HT2C,5 HT3,5 HT6 和 5 HT7受体亚型mRNAs在大鼠脊髓不同节段的表达。 方法 :反转录PCR方法。 结果 :5 HT2C受体亚型mRNA在颈、胸、腰、骶段脊髓的背角 (DH)和前角 (VH)均有较强的表达 ;5 HT3受体mRNA在各节段脊髓DH的表达水平较高 ,而在VH则较低 ;与 5 HT3受体亚型相反 ,5 HT6 受体亚型mRNA在脊髓VH的表达水平高于DH ;5 HT7受体mRNA在脊髓的表达则与 5 HT3受体相似 ,在各节段的DH均有较高水平的表达。不同的受体亚型在脊髓同一节段以及同一受体亚型在不同脊髓节段的表达水平存在差异。结论 :本研究结果表明 ,上述四种 5 HT受体亚型在脊髓具有不同的表达特点 ,提示它们在脊髓水平可能发挥着不同的生理作用 ,并为深入探讨 5 HT受体参与伤害性感受和运动的调节机制提供了依据。

Anti-Anxiety Effects of Prelimbic 5-HT4 Receptors in the Rat Model of Parkinson’s Disease: Evidence from Behavioral and Electrophysiological Study

Objective:Clinical and laboratory studies have demonstrated that prelimbic(PrL)and serotonin-4(5-HT4)receptors may have the key role in regulating anxiety.However,the pathophysiology of anxiety in Parkinson’s disease(PD)remains obscure.In this research,the effects of PrL 5-HT4 receptors on anti-anxiety behaviors in hemiparkinsonian rats were investigated.Methods:PD model rats were used as the research subjects,starting with behavioral changes,from the point of view of electrophysiology,the regulatory effect of PrL 5-HT4 receptors on PD-related anxiety and the possible mechanism were explored.Results:Anxiety-like behaviors were induced via MFB lesion in rats.Intra-PrL injection of 5-HT4 receptors agonist RS67333 induced anti-anxiety effects in both sham and PD group.In the sham group,PrL administration of 5-HT4 receptors antagonist SB204070 produce anti-anxiety effects,but in the PD group,the expression of anxiety-like behavior was increased.Compared to the sham group,the effective dose of the behavioral effects of the two drugs in the PD group was obviously higher.Electrophysiological data suggested that PrL administration of RS67333(SB204070)increased(decreased)the firing activities ofγ-aminobutyric acid(GABA)neurons in both groups.Compared with rats in sham group,lesioned rats had a shorter duration of the excitation(inhibition)effects on firing activities of GABA neurons.Conclusion:PrL 5-HT4 receptors regulate anxiety behaviors in PD rats,and its mechanism may be related to the down-regulation of expression or function of PrL 5-HT4 receptors in PD.

阿瑞匹坦联合5-HT_3受体拮抗剂和地塞米松预防化疗相关性恶心和呕吐的Meta分析

目的:采用Meta分析方法对阿瑞匹坦联合5-HT3受体拮抗剂和地塞米松预防化疗相关性恶心和呕吐进行系统评价。方法:检索Pubmed、EMbase、Cochrane Library、中国知网CNKI全文数据库、维普数据库、万方数据库和中国生物医学文献数据库,查找2003年1月至2013年12月公开发表的研究阿瑞匹坦联合5-HT3受体拮抗剂和地塞米松预防化疗相关性恶心和呕吐的临床随机对照试验。按照纳入与排除标准选择文献,质量评估,资料提取,采用Rev Man 5.2软件进行Meta分析。结果:共纳入12篇英文RCT文献,均为高质量研究。Meta分析结果显示,阿瑞匹坦联合5-HT3受体拮抗剂、地塞米松治疗(三联治疗)在预防高、中度致吐性化疗相关性恶心和呕吐的总体完全缓解率[OR=1.91,95%CI(1.68,2.17),P<0.00001]、急性完全缓解率[OR=1.89,95%CI(1.48,2.42),P<0.00001]、迟发性完全缓解率[OR=2.05,95%CI(1.68,2.51),P<0.00001]明显高于5-HT3受体拮抗剂、地塞米松治疗(二联治疗),两组差异有统计学意义。结论:阿瑞匹坦可以显著提高高、中度致吐性化疗的总体、急性和迟发性恶心和呕吐完全缓解率,尤其是在提高迟发性恶心和呕吐完全缓解率更为明显。

不同剂量5-HT_3受体拮抗剂格拉司琼防治围术期恶心呕吐的临床研究

目的观察不同剂量的5-HT3受体拮抗剂格拉司琼(ranisetron)对围术期恶心呕吐(PONY)的作用时效,以寻求合适的剂量预防和减少PONY的发生。方法择期上腹部吸入全麻手术患者120例,随机双盲分成生理盐水对照组(A组)、昂丹司琼8mg组(B组)、格拉司琼3mg(C组)及6mg(D组),每组各30例。术毕观察给止吐药至第1次出现恶心呕吐的时间、各组发生恶心呕吐的患者数、接受补救药物的患者数、恶心的严重程度、患者对止吐药物的满意度、头晕头痛、椎体外系症状等不良反应等。结果各组患者性别、体重、年龄、麻醉持续时间、术中生命体征等各组间比较差异无统计学意义(P>0.05)。各组发生恶心、呕吐和接受补救药物患者数,初次出现恶心的时间,恶心严重程度评级的比较中,格拉司琼均优于昂丹司琼,差异有统计学意义(P<0.05);格拉司琼3mg及6mg头晕头痛的发生率相近,均低于昂丹司琼,差异有统计学意义(P<0.05)。结论(1)格拉司琼的镇吐效果优于昂丹司琼;(2)格拉司琼3mg不仅可以减少药物用量、增强抗吐时效,而且能减少不良反应的发生,是一种安全有效的止吐方法。

白芍提取物对经前期综合征肝气郁证模型大鼠额叶5-HT_(3A/3B)R分布与蛋白表达的影响

目的:本研究就5-羟色胺3受体(5-HT3R)水平探讨白芍提取物(Radix Paeoniae Alba Extract,RPAE)干预经前期综合征(Premenstrual Syndrome,PMS)肝气郁证抑郁情绪的分子作用机制。方法:复制PMS肝气郁证大鼠模型,用白芍提取物进行药物干预,采用免疫荧光技术和蛋白印迹技术(western blot)分别检测5-HT3AR和5-HT_(3B)R在大鼠脑内的分布和蛋白表达情况。结果 :5-HT_(3A)R和5-HT_(3B)R在各组大鼠额叶均有阳性表达;与正常组大鼠相比,模型组大鼠额叶5-HT3AR、5-HT_(3B)R蛋白表达水平均显著升高(P<0.05);与模型组大鼠相比,白芍提取物组大鼠额叶5-HT_(3A)R蛋白表达水平均显著下降(P<0.05)。结论:白芍提取物能够调控PMS抑郁症大鼠额叶5-HT_(3A) R和5-HT_(3B)R蛋白表达,这可能是其干预PMS肝气郁证抑郁情绪的作用机制之一。

大鼠杏仁核5-HT_3受体参与免疫调制

实验通过大鼠侧脑室和杏仁核给予 5 HT3受体激动剂 1 phenylbiguanide (PBG) ,用 3H TdR掺入法测定脾细胞丝裂原 (concanavalinA ,ConA和lipopolysaccharide ,LPS)刺激增殖效应 ,用活化脾细胞增殖法测定IL 2生成 ,MTT法测定自然杀伤 (naturalkiller,NK)细胞活性和用放射免疫测定血浆皮质酮水平 ,以探讨大鼠杏仁核 5 HT3受体在免疫调控中的作用。结果表明 :5 HT3受体拮抗剂granisetron (GNT ,0 1～ 0 4mg/kgip)剂量依赖地增强ConA和LPS刺激的脾细胞增殖 ,作用在连续给药 5d最明显 ;双侧脑室给予PBG ( 5 μg/side)可增强ConA和LPS刺激的脾细胞增殖效应 ,作用在连续给药 3d最明显 ;双侧和单侧中央杏仁核给予PBG 0 5 μg均增强ConA刺激的脾细胞增殖和IL 2生成 ;底内侧杏仁核给予同剂量PBG仅增强LPS刺激的脾细胞增殖效应 ,不影响ConA刺激的脾细胞增殖和IL 2生成 ;中央杏仁核给予PBG升高血浆皮质酮的作用较底内侧杏仁核给予等量PBG引起的升高血浆皮质酮作用明显 (P <0 0 1)。侧脑室、中央杏仁核和底内杏仁核给予PBG对丝裂原刺激的脾细胞增殖效应影响不同 ,但均被同时同部位给予GNT所拮抗 ,提示杏仁核中央核和底内侧核的 5