莉芙敏对去卵巢大鼠下丘脑视前区5-HT1AR和5-HT2AR表达的影响

目的:观察去卵巢大鼠应用黑升麻异丙醇提取物--莉芙敏(ICR)治疗1-4周后,免疫组化方法检测5-羟色胺1A受体(5-HT1AR)和5-HT2AR在大鼠下丘脑视前区表达的变化情况,为莉芙敏缓解围绝经期潮热症状的机制研究提供形态学依据.方法:雌性大鼠分为假手术组(Sham组)、去卵巢组(OVX组)、OVX后戊酸雌二醇治疗...     

替勃龙上调卵巢切除大鼠腰椎护骨素mRNA的表达

目的:建立绝经后骨质疏松(postmenopausalosteoporosis,PMOP)的大鼠模型,研究替勃龙对卵巢切除大鼠腰椎组织中护骨素(OPG)基因mRNA表达水平的影响,探讨其预防和治疗PMOP的作用机制。方法:6月龄未交配健康雌性SD大鼠40只,随机分为SHAM组,OVX组,OVX+戊酸雌二醇(E2)组和OVX+替勃龙(tibolone,TIB)组。灌胃13周后处死动物,第四腰椎行骨组织形态计量指标测定,第二腰椎采用RT-PCR方法,对OPGmRNA表达水平进行检测。结果:OVX组大鼠较SHAM组TBV%显著下降;OSV%明显升高(P<0·05);E2和TIB均可使OVX大鼠的TBV%明显升高,OSV%明显下降;OPGmRNA表达水平在OVX大鼠组织中下调,与SHAM组相比有显著性差异(P<0.05),E2和TIB均可上调OVX大鼠骨组织OPGmRNA表达水平(P<0.05)。结论:E2和TIB均通过抑制骨转换预防和治疗PMOP;PMOP的发生与OPG有关,TIB和E2一样,其抗骨吸收效应很可能是通过OPG介导的。     

17β-雌二醇对去势大鼠神经系统的作用

目的：研究补充外源性雌激素对去势大鼠海马和皮质组织中核转录因子2/血红素加氧酶1（Nrf2/HO-1）、沉默信息调节因子相关酶1（SIRT1）表达含量及大鼠海马和皮质区域神经元排列形态和数量的影响,探讨雌激素对神经系统的作用。方法：选取清洁级3个月龄Sprague-Dawley（SD）雌性大鼠40只,随机分为4组。空白组（CON组）、假手术组（SHAM组）、去势对照组（OVX组）、去势实验组（OVX+E2组）,每组10只。OVX+E2组给予17β-雌二醇（E2）灌胃,其余3组予生理盐水灌胃。16周后测定各组大鼠海马和皮质组织中的Nrf2、HO-1、SIRT1表达量,同时对大脑皮质及海马CA1区域神经元行形态学检查。结果：①OVX组大鼠海马及皮质中Nrf2、HO-1水平高于SHAM组,SIRT1水平低于SHAM组;OVX+E2组大鼠海马及皮质中Nrf2、SIRT1水平高于OVX组,HO-1水平则低于OVX组;②OVX+E2组海马及皮质组织中神经元数量及排列情况与SHAM组无明显差异,而OVX组海马及皮质尼氏体数量减少,神经元排列紊乱。结论：补充外源性雌激素可下调去势大鼠海马及皮质中HO-1表达,上调Nrf2、SIRT1表达,维持神经元数量及排列结构,从而保护神经系统。     

雌二醇、G蛋白耦联雌激素受体激动剂和抑制剂对去势大鼠5-羟色胺水平的影响

目的探索雌激素对去势大鼠血清5-羟色胺(HT)水平的影响,以及G蛋白耦联雌激素受体(GPER)在其中发挥的作用。方法健康12周龄性成熟雌性大鼠50只,随机分为10组,每组5只。其中30只通过卵巢去势手术建立绝经大鼠模型,20只行假手术作为对照组。去势大鼠再分为6组,分别注射1周的雌二醇(E_2)组、E_2+GPER特异性激动剂(G1)组、G1组、抑制剂(G15)组、E_2+G15组、油剂组;假手术大鼠分别注射1周的G1组、G15组、空白组、油剂。于手术前及用药前后分别进行心脏采血,采用酶联免疫吸附法(ELISA)检测血清中5-HT的水平。结果大鼠卵巢去势手术后5-HT水平显著降低(P=0.031),假手术后5-HT水平无显著变化(P=0.380)。卵巢去势的大鼠在连续注射1周E_2后,5-HT水平显著升高(P=0.007)。单独注射G1或G15及E_2+G1或E_2+G15 1周后,5-HT水平变化均无统计学意义。结论大鼠卵巢去势后血清5-HT水平显著降低,而使用雌激素治疗使5-HT水平升高,G1和G15治疗1周对大鼠5-HT水平没有显著影响。     

替勃龙联合更安宁对雌性去势大鼠血管内皮细胞的保护作用

目的:观察替勃龙联合补肾中药(更安宁)在雌性去势大鼠加高脂饮食状态下,对血管内皮细胞的保护作用。方法:9月龄雌性Sprague-Dawley大鼠50只,随机分为假手术组(SHAM)、卵巢切除组(OVX)、卵巢切除后药物联合治疗组(OVX+E)、高脂血症组(OVX+HC)、高脂血症药物联合治疗组(OVX+HC+E)。在卵巢切除术后14d起,OVX组、OVX+HC组给予生理盐水灌胃,OVX+E组、OVX+HC+E组予替勃龙+补肾中药更安宁溶液灌胃,OVX+HC组、OVX+HC+E组同时喂饲高脂饮食。12周后处死大鼠,测定血浆雌二醇(E2)、高密度脂蛋白(HDL-c)、低密度脂蛋白(LDL-c)、胆固醇(Tch)、甘油三脂(TG)、一氧化氮(NO)、血管性假性血友病因子(vWF),在光镜及电镜下观察主动脉管壁结构的改变。结果:OVX+E组与OVX组相比,OVX+HC+E组与OVX+HC组相比,均表现Tch、LDL-c明显降低,HDL-c明显升高,血浆NO含量增加;OVX组存在轻度动脉粥样硬化坏死,OVX+HC组动脉管壁损伤严重,伴随vWF明显升高;OVX+E组与OVX+HC+E组动脉管壁结构正常。结论:替勃龙联合补肾中药更安宁治疗能保护血管内皮细胞,对抗高脂血症对动脉管壁的损伤。     

环境温度变化对去卵巢大鼠下丘脑视上核和室旁核c-Fos蛋白表达的影响

目的:以不同温度刺激去卵巢大鼠,观察下丘脑视上核(SO)和室旁核(PVN)细胞c-Fos蛋白表达的变化,探讨更年期妇女血压、渗透压以及体温调节功能异常的可能机制.方法:将去卵巢(OVX)和假手术(Sham)大鼠分别置于4,10,25,33和38℃5个温度等级的培养箱内,2 h后取脑.采用免疫组织化学法检测各实验组SO和...     

大豆苷元对去卵巢大鼠血脂及肝脏ERα和LDLR表达的影响

目的:探讨不同剂量大豆苷元对绝经后血脂的保护作用。方法:选用4月龄SD雌性大鼠66只,随机分为:假手术组(Sham)、去势组(OVX)、戊酸雌二醇组(E2)、大豆苷元高剂量(H-Dai,200mg/kg)组、中剂量(M-Dai,50mg/kg)组和低剂量(L-Dai,10mg/kg)组,每组11只。于去势术后4周开始分别给予相应的药物灌胃,3个月后处死大鼠,取血和肝脏,检测血清甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-c)、高密度脂蛋白胆固醇(HDL-c),以及肝脏ERα和LDLRmRNA的表达量。结果:与OVX组相比,大豆苷元可以降低血清LDL-c,且随着剂量的增加其作用更明显(P<0.01);大剂量可以降低血清TG(P<0.05)。大豆苷元还增加肝脏ERα和LDLRmRNA的表达量,且也有剂量依赖效应,低、中剂量组与高剂量组差异显著(P<0.01)。结论:大豆苷元对去势大鼠血脂有一定保护作用,其降低血清LDL-c的作用可能是通过ERα途径增加LDLR的表达而实现的。     

绝经期潮热与5羟色胺

潮热是围绝经期和绝经期最常见症状，其确切的发病机制不明。可能是雌激素水平下降引起中枢神经递质改变，导致下丘脑体温调定点改变所致。其最有效的治疗是雌激素替代疗法(ERT)。但因ERT使用禁忌证及对ERT的争议，促使寻求新的非激素疗法。近来研究发现，5羟色胺(5-HT)再摄取抑制剂(SSRI’s)及其类似物能安全有效地缓解潮热，同时以潮红为主要症状的嗜铬细胞瘤患者血中含有高浓度的5-HT，口服SSRI’s后可以消除和缓解症状。提示绝经期潮热可能和5-HT有关，特别是5-HT2A受体亚型可能在潮热发生中起关键作用。     

绝经期潮热与5羟色胺

潮热是围绝经期和绝经期最常见症状,其确切的发病机制不明.可能是雌激素水平下降引起中枢神经递质改变,导致下丘脑体温调定点改变所致.其最有效的治疗是雌激素替代疗法(ERT).但因ERT使用禁忌证及对ERT的争议,促使寻求新的非激素疗法.近来研究发现,5羟色胺(5-HT)再摄取抑制剂(SSRI's)及其类似物能安全有效地缓解潮热,同时以潮红为主要症状的嗜铬细胞瘤患者血中含有高浓度的5-HT,口服SSRI's后可以消除和缓解症状.提示绝经期潮热可能和5-HT有关,特别是5-HT2A受体亚型可能在潮热发生中起关键作用.     

醒脑开窍针刺法治疗产后抑郁的临床疗效

目的：探讨醒脑开窍针刺法治疗产后抑郁（postpartum depression,PPD）的效果。方法：选取2022年1—9月石家庄市妇幼保健院收治的PPD患者80例,采用随机数字表法分为2组,每组各40例。对照组给予常规西药治疗,观察组给予醒脑开窍针刺法结合西药治疗,疗程为8周。统计2组患者的疗效、安全性,并比较2组患者治疗前、后的抑郁程度[汉密尔顿抑郁量表（Hamilton Depression Scale,HAMD）、爱丁堡产后抑郁量表（Edinburgh Postnatal Depression Scale,EPDS）]、性激素水平[孕酮（progesterone,P）、雌二醇（estradiol,E2）]和神经递质水平[5-羟色胺（5-hydroxytryptamin,5-HT）、孤啡肽（OFQ）]。结果：观察组的疗效和总有效率均高于对照组,差异有统计学意义（P<0.05）;治疗8周后,2组患者的HAMD、EPDS评分及OFQ水平均较治疗前下降,观察组低于对照组,2组P、E2、5-HT水平均较治疗前升高,观察组高于对照组,差异有统计学意义（P<0.05）。结论：醒...     

5-羟色胺对人胎盘滋养细胞钙通道的影响

目的探讨5-羟色胺对胎盘滋养细胞钙通道的影响。方法将体外培养的胎盘滋养细胞分成3组,低深度5-羟色胺组(5-TH,1μmol/L)、高浓度5-TH组(10μmol/L)和对照组。采用全细胞膜片钳方法,在胎盘滋养细胞外液中分别加入L-型钙通道阻滞剂、T-型钙通道阻滞剂、钠通道阻滞剂及5-TH,检测其电流值。结果在-60～-50mV电压时,胎盘滋养细胞L-型钙通道开放,-40～-30mV时,其最大峰值电流为(82.31±6.46)皮安(pA)。加入尼莫地平(Nimodpine)可阻断大部分电流。氟桂利嗪(Flunari-zne)和替曲朵辛(TTX)不能抑制该电流成分。加入1μmol/L和10μmol/L5-TH,其峰值电流分别为(104.77±10.84)pA和(117.16±9.67)pA,与对照组比较,差异有统计学意义(P0.05);加入5-TH(1μmol/L)和Nimodpine、5-TH(10μmol/L)和Nimodpine后,峰值电流分别为(85.35±6.54)pA和(89.42±7.62)pA,与对照组比较,差异无统计学意义(P0.05)。结论5-TH可激活胎盘滋养细胞L-型钙通道,促使钙电流值增加。     

Role of 5-HT Receptor Antagonists in Mediating Intracavernous Pressure Response Induced by Fluvoxamine in Conscious Rats

IntroductionIt has been reported that selective serotonin reuptake inhibitor (SSRI) may cause sexual dysfunction.AimTo determine the relationship between serotonin and sexual function, we investigated the role of serotonergic receptors on changes in intracavernous pressure (ICP) and systemic blood pressure (BP) in conscious and free-moving rats.MethodsICP and BP were measured in male Sprague-Dawley rats after catheters were inserted into the crus corpus cavernosum and carotid artery, respectively. Pressures were recorded 2 hours after catheterization. In other rats, this procedure was performed 2 weeks after spinal cord transection (spinal cord injury [SCI]) between the eighth and ninth thoracic vertebrae. To investigate the role of serotonergic receptors, fluvoxamine (an SSRI), WAY100635 (a 5-HT_1A-receptor antagonist), and SB242084 (a 5-HT_2C-receptor antagonist) were administered by intravenous (i.v.) or intracerebroventricular (i.c.v.) routes.Main Outcome MeasuresBP and parameters of ICP were measured in conscious and free-moving rats.ResultsAdministration of fluvoxamine (1- to 30-μmol/kg i.v. and 1- to 30-nmol i.c.v.) induced a transient increase in the ICP. The ICP parameters responded in a dose-dependent manner, especially the time to first response (TFR), which was significantly shortened. BP also increased in response to fluvoxamine. In contrast, ICP in SCI rats did not change after fluvoxamine administration. WAY100635 (10 or 30-nmol i.c.v.) induced an increase in the ICP. In combination with fluvoxamine, it significantly shortened the TFR in comparison with WAY100635 or fluvoxamine alone. However, SB242084 (10 or 30-nmol i.c.v.) actually had an inhibitory effect on fluvoxamine-induced ICP responses.ConclusionsThese findings demonstrated that ICP is regulated at the supraspinal level when endogenous serotonin is increased by fluvoxamine. Furthermore, ICP is facilitated by 5-HT_2C-receptors and inhibited by 5-HT_1A-receptors in the rat brain. Aizawa N, Ishizuka O, Ogawa T, Mizusawa H, Igawa Y, and Nishizawa O. Role of 5-HT receptor antagonists in mediating intracavernous pressure response induced by fluvoxamine in conscious rats.     

Moderate Role of Oxytocin in the Pro-Ejaculatory Effect of the 5-HT1A Receptor Agonist 8-OH-DPAT

IntroductionThe neurobiological control of ejaculation is not completely understood. Both serotonin (5-HT) and oxytocin (OXT) play a role in the control of male sexual parameters, putatively via overlapping neuronal networks.AimThe aim of this study was to determine whether activation of 5-HT_1A receptors (5-HT_1ARs) reduces the ejaculatory threshold via the direct activation of (OXT) neurons in the paraventricular hypothalamic nucleus (PVN).MethodsIn experiment 1, male rats received acute bilateral infusions of the selective 5-HT_1AR antagonist WAY-100635 (1 and 10 μg) or vehicle into the PVN, followed by acute subcutaneous (SC) injection of the potent 5-HT_1AR agonist 8-OH-DPAT (0.4 mg/kg) or saline. In experiment 2, male rats received acute bilateral infusions of 8-OH-DPAT (1 and 10 μg) or vehicle into the PVN. In experiment 3, male rats received acute intracerebroventricular (ICV) infusion of a selective OXT receptor antagonist (OXTR-A, 75 and 750 ng) followed by acute SC injection of 8-OH-DPAT (0.4 mg/kg) or saline. The effects of these drug treatments on sexual behavior were measured.Main Outcome MeasuresCopulation latency, ejaculation latency, mount and intromission frequency, and ejaculation frequency of sexually experienced adult male Wistar rats during 30-minute sexual behavior tests with a receptive female were the main outcome measures.ResultsMale sexual behavior was not affected by intra-PVN infusion of WAY-100635 or 8-OH-DPAT, or by ICV infusion of OXTR-A alone. However, the facilitation of ejaculation (reduced mount and intromission frequency and ejaculation latency) induced by systemic 8-OH-DPAT could be attenuated by either intra-PVN infusion of WAY-100635 or by ICV infusion of OXTR-A.ConclusionsActivation of OXT neurons plays a moderate role in the pro-ejaculatory effects of systemic 8-OH-DPAT, but extracellular 5-HT levels may influence the strength of the effects. de Jong TR and Neumann ID. Moderate role of oxytocin in the pro-ejaculatory effect of the 5-HT_1A receptor agonist 8-OH-DPAT. J Sex Med 2015;12:17–28.     

Expression of placental serotonin transporter and 5-HT 2A receptor in normal and gestational diabetes mellitus pregnancies

Recent studies reveal that serotonin (5-hydroxytryptamine, 5-HT) might play a role in the aetiology of gestational diabetes mellitus (GDM). The involvement of the serotonin transporter (SERT) and 5-HT_2A receptor (5-HT_2AR) in diabetes has also been suggested. However, placental SERT and 5-HT_2AR have never been studied in GDM-complicated pregnancies. The aim of this study was to investigate the effect of GDM on the expression of both placental SERT and 5-HT_2AR. First, immunohistochemical analysis demonstrated the presence of SERT and 5-HT_2AR proteins in the villous trophoblast and the fetal capillary endothelium of normal term placental tissue. Protein and mRNA expression of SERT and 5-HT_2AR in the villous cytotrophoblastic and syncytiotrophoblastic cells was further confirmed in primary culture. A significantly (P < 0.05) decreased expression of SERT mRNA (56.3%) and protein (79.7%), and 5-HT_2AR mRNA (79.1%) and protein (29.1%) was observed in placental tissues from GDM compared with non-GDM pregnancies. These data suggest that SERT and 5-HT_2AR might be implicated in the aetiology of GDM. Moreover, the presence of SERT and 5-HT_2AR in villous trophoblastic cells argues in favour of an important role of serotonin in human placental function.     

Serotonin Transporter Null Mutation and Sexual Behavior in Female Rats: 5-HT1A Receptor Desensitization

IntroductionSerotonin plays a key role in sexual behavior. In serotonin transporter (SERT) knockout rats (?/?), basal extracellular 5-HT levels are considerably increased, indicating a serotonergic disturbance. Heterozygous SERT(+/?) rats express 50% of SERT in comparison to wild-type rats and may therefore model the s/s phenotype of the human SERT promoter (5-HTTLPR) polymorphism.AimIn the present study, we used both homozygote and heterozygote SERT knockout and wild-type rats (+/+) to study the putative role of the SERT in female sexual behavior.MethodsFemale rats were brought into estrous by hormonal injections before a paced mating sex test. The effects of the 5-HT_1A/5-HT₇ receptor agonist (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (±8-OH-DPAT) (0.03–1 mg/kg s.c.) and the 5-HT_1A receptor antagonist WAY-100635 (0.1–1–mg/kg i.p.) on sexual behaviors of the females were tested separately and in a selected combination of both in all three genotypes.Main Outcome MeasuresProceptive (darting and hopping) and receptive (lordosis) behaviors were quantified.ResultsBasal proceptive and receptive sexual activities were not different between SERT+/+, +/? and ?/? female rats. The dose–effect curve after ±8-OH-DPAT for these activities was clearly shifted to the right in SERT?/? animals compared to other genotypes. WAY-100635 alone had no effect on sexual behavior in any genotype, but was able to antagonize the ±8-OH-DPAT-induced decrease in sexual activities indicating the involvement of the 5-HT_1A receptor.ConclusionsThe absence (?/?) or reduced (+/?) expression of SERT does not affect basal sexual activity in female rats in a paced mating situation. The data indicate a desensitized 5-HT1A receptor in the SERT?/?, but not in the SERT+/? females. Under normal basal conditions, desensitized 5-HT1A receptors apparently do not play a role in female sexual behavior of the SERT?/?. However, upon activation of the 5-HT1A receptor in “normal” females (SERT+/+ and SERT+/?), a hyposexual behavior is induced. Snoeren E, Chan J, Bovens A, Cuppen E, Waldinger M, Olivier B, and Oosting R. Serotonin transporter null mutation and sexual behavior in female rats: 5-HT1A receptor desensitization.