盐酸氟西汀对抑郁症模型小鼠神经肽Y表达的研究

目的 探讨盐酸氟西汀对慢性应激抑郁症模型小鼠下丘脑神经肽Y（NPY）的表达影响。方法 采用旷场试验（Open-Field）法，比较抑郁症模型小鼠与正常对照组行为学改变方面的差异。将慢性应激抑郁症小鼠模型随机分成盐酸氟西汀和阿米替林治疗组、模型对照组，同时设立空白对照组，利用半定量逆转录．聚合酶联反应（RT-PCR）法、细胞酶联免疫法和蛋白免疫印迹（Western-blot）技术，比较试验组小鼠下丘脑NPY的表达变化。结果 （1）与正常组比较，模型组在总路程缩短、活动斑数减少和体重增加幅度下降等方面具有显著性差异。（2）与正常组比较，抑郁症模型组下丘脑NPY的mRNA表迭下降。（3）经过3周的治疗，盐酸氟西汀组和阿米替林组小鼠下丘脑NPY的mRNA及蛋白表达没有明显差别，但是两组的表达结果显著高于模型对照组，与空白对照组的结果接近。结论 脑内NPY的mRNA及蛋白的表达增加可能是盐酸氟西汀治疗抑郁症小鼠的机制之一。     

Effects of capsaicin in temporomandibular joint arthritis in rats

Temporomandibular joint (TMJ) arthritis was induced in female Lewis rats by unilateral injection of a suspension of heat-killed Mycobacterium butyricum in paraffin oil into the TMJ. Control rats received paraffin oil by the same route. Arthritic and control rats were pretreated either with capsaicin or denervation of the mandibular branch of the trigeminal nerve. Tissues were collected for neuropeptide extraction and analysed by radioimmunoassay and reverse-phase high-performance liquid chromatography. In all groups, the levels of substance P- (SP), calcitonin gene-related peptide- (CGRP) and neuropeptide Y- (NPY) like immunoreactivity (LI) were higher in the trigeminal ganglia than in the TMJs. In control rats, capsaicin significantly lowered the levels of SP-LI in the trigeminal ganglia and TMJ, but not CGRP-LI and NPY-LI. In the arthritic rats, capsaicin pretreatment significantly lowered the SP-LI and CGRP-LI in the trigeminal ganglia and TMJ, but not the NPY-LI. In the trigeminal ganglia the unilateral denervation significantly lowered SP-LI in control rats, and in arthritic rats SP-LI and CGRP-LI. On the denervated side of the arthritic TMJ, NPY-LI, SP-LI and CGRP- LI were significantly lowered as compared to the arthritic control rats and to the contralateral side. In this rat model, pretreatment with capsaicin and surgical denervation decreased the neuropeptide content in the trigeminal ganglia and the TMJ. The results clearly demonstrate a close interaction between increased neuropeptide release from sensory and sympathetic neurones after induction of arthritis in the rat.     

神经肽Y标记神经元在大鼠脑桥的分布

目的:观察了神经肽Y（NPY）样神经元在大鼠脑桥的分布,为探讨脑桥NPY样神经元的功能提供实验形态学依据。方法:免疫组织化学方法（PAP法）。结果:在脑桥可见到前庭神经上核、耳蜗神经腹侧核及脑桥尾侧网状核NPY样免疫反应胞体。前庭神经上核的NPY样胞体较多且密集,细胞大小均匀,呈梭形或椭圆形,有明显突起;耳蜗神经腹侧核内的NPY样胞体呈大小均匀分布,圆形且较小,突起不明显;脑桥尾侧网状核内的NPY样胞体分布较稀疏,且大小不一,呈菱形或梭形,有明显较长的突起。结论:NPY样神经元不仅广泛存在于端脑和下丘脑,在脑桥也同样有着广泛的分布。     

大颗粒小泡非突触部位的胞吐——论神经肽释放的另一种形式

本文在以前的工作基础上,进一步用电镜及免疫细胞化学方法,研究了大颗粒小泡非突触部位胞吐作用。实验结果表明,切除大鼠刚髭部皮肤1—24小时之后,术侧延髓后角浅层大颗粒小泡胞吐比对照侧明显增多(P<0.01),术后3—9天复又下降(近似对照动物),术后14—15天又急剧上升(P<0.01)。这些胞吐大部分出现于延髓后角浅层四种轴突终末的非突触部位,少最也发生于树突及轴突中。从术后第6天开始,术侧P物质明显减弱,而甲硫-脑腓肽略有增强。研究结果提示;1)后角浅层胞吐增多,P物质下降及脑腓肽增高,反映了中枢内不同神经元对去传入神经的功能调整作用;2)大颗粒小泡在非突触部位释放神经肽,弥散地作用于远距离的受体,可能起着神经调制物的作用。     

神经肽Y对免疫细胞活性的影响

神经肽Y（NPY）是广泛分布于中枢神经系统和外周神经各部位的神经肽类物质。本实验观察NPY在体外对几种免疫细胞活性的直接作用。结果表明，NPY对小鼠T淋巴细胞丝裂原反应性和NK细胞的杀伤活性均无明显影响（P＞0．05），对巨噬细胞分泌溶菌酶有明显抑制作用（P＜0．05）；而对B淋巴细胞丝裂原反应性则有明显的促进作用（P＜0．05）。上述结果提示，NPY对部分免疫细胞功能的影响因细胞种类而异。     

Nociceptin (Orphanin FQ) abolishes gestational and ovarian sex steroid-induced antinociception and induces hyperalgesia

Nociceptin (Orphanin FQ) is a newly discovered endogenous heptadecapeptide substrate for the opioid-receptor-like 1 receptor, a G protein coupled receptor that bears striking amino acid sequence homology to opiate receptors. In rats, intrathecal (i.t.) administration of nociceptin is without effect on basal thresholds for responsiveness to electric foot shock. However, during either late gestation or its hormonal simulation, when nociceptive thresholds are elevated by approximately 70%, i.t. nociceptin substantially attenuates jump thresholds in a dose-dependent fashion. This hypoalgesic effect of nociceptin is not limited to attenuating the gestational or sex steroid-induced increment in pain thresholds. Following the highest i.t. dose of nociceptin employed (20 nmol), the gestational or sex steroid-induced increment in jump thresholds is not only abolished but a significant hyperalgesia is observed. These results underscore the importance of the hormonal milieu to nociceptin hypoalgesic sensitivity. The potential contribution of spinal nociceptive pathways that utilize nociceptin to the etiology of extraordinary painful pregnancy and labor should not be ignored.     

β—内啡肽增强人外周血单个核细胞IL—2和IFN—γmRNA的表达

应用逆转录-多聚酶链反应及Sonthern杂交技术，研究卜内啡肽（β-END）对PHA诱导的人外周血单个核细胞IL－2和IFN－ΥmRNA表达的调节作用。结果发现β-END（10-8～10-14mol／L）可显著增强IL－2和IFN－ΥmRNA的表达并呈剂量依赖性关系，此外发现β-END对IL－2mRNA的增强作用可被阿片肽受体桔抗剂——纳络酮逆转。本研究从基因水平上证明了神经递质可通过影响免疫细胞细胞因子调节免疫功能。     

A Thalamic Contribution to Arousal-induced, Non-photic Entrainment of the Circadian Clock of the Syrian Hamster

It is well established that the circadian clock of the suprachiasmatic nuclei (SCN) is entrained by light. More recently, the potent effects of arousing, non-photic cues on the clock have been recognized. The neural mediators of non-photic entrainment are yet to be identified. To examine the contribution of the thalamic intergeniculate leaflet (IGL) and its NPY-immunopositive projection, the geniculo-hypothalamic tract to non-photic entrainment by arousal, male Syrian hamsters received lesions of the IGL (IGLX) which ablated NPY-immunoreactivity in the SCN. Their circadian responses to both photic and non-photic cues were then tested. Lesions resulted in a delay in the timing of activity onset following lights out, but had no effect on the behavioural or cellular circadian responses to phase-advancing light pulses presented at circadian time (CT) CT19 (where CT12 represents the time of activity onset). Injection with a benzodiazepine (chlordiazepoxide, 100 mg/kg) at CT6 suppressed wheel-running, increased general locomotion of intact controls and induced large phase advances of the circadian rhythm of wheel-running. Chlordiazepoxide also inhibited wheel-running in lesioned animals, but there was no significant increase in general locomotion and the lesioned animals did not phase advance. Serial arousal by injection of saline at intervals of 23.5 h for 6 days entrained the circadian rhythm of wheel-running of intact hamsters and was associated with an increase in general locomotor activity. Entrainment by serial arousal was abolished by IGLX. However, the lesioned animals did show a clear behavioural response to every presentation of the non-photic cue. These results show that the IGL is a necessary component of the neural pathways mediating both arousal- and benzodiazepine-induced non-photic entrainment.     

Prevention of arginine-vasopressin-induced motor disturbances by a potent vasopressor antagonist

The antivasopressor analog d(CH2)5Tyr(Me) arginine-vasopressin completely blocked the convulsive-like behavior and other severe motor disturbances which are normally observed following a second central arginine-vasopressin injection. This vasopressor antagonist appears to be selective for arginine-vasopressin-induced motor disturbances, in that the convulsive and motor effects of pentylenetetrazol and somatostatin were not altered significantly by pretreatment with the central antagonist. Results suggest that arginine-vasopressin-induced motor disturbances are mediated via central receptors. The classic antidiuretic (V2) type of arginine-vasopressin receptor does not appear to be involved, since the agonist 1-desamino-8-D-arginine-vasopressin did not elicit convulsive-like behavior or other severe motor disturbances 2 days following a first ('priming') injection of arginine-vasopressin.