神经肽类

摘要： 雌性哺乳动物的生殖受下丘脑-垂体-卵巢(hypothalamus-pituitary-ovary,HPO)轴调控,外周和中枢的诸多刺激因子参与其中并组成复杂的调节网络。哺乳动物下丘脑神经肽RF酰胺相关肽3(RFamide-related peptide 3,RFRP-3)是下丘脑中的HPO轴抑制因子,通过G蛋白耦联受体147(G protein-coupled receptor 147,GPR147)对HPO生殖轴产生抑制信号,并与其他神经肽协同影响哺乳动物交配行为和生殖活动。此外,RFRP-3具有调节下丘脑能量稳态信号的作用。目前对于RFRP-3在雌性哺乳动物代谢稳态以及生殖活动中的特定内源性作用研究者还未达成主要共识。故综述近年RFRP-3在雌性哺乳动物能量平衡、应激调节和生殖功能3个方面的作用,以期为哺乳动物的生殖及代谢相关疾病的发病机制及治疗干预措施提供新的见解。

摘要： Considerable evidence has indicated that psychological factors,such as anxiety,nervousness and mental stress,can induce or exacerbate psoriasis and affect therapeutic effects to a certain degree,suggesting that psychological factors may play an important role in the occurrence of psoriasis.Current researches on neuropsychiatry-related pathogenesis of psoriasis mainly include two aspects:on the one hand,acting as stressors,psychological factors can activate the following two neuroendocrine systems,including hypothalamic-pituitary-adrenocortical axis and sympathetic-adrenal medullary system;on the other hand,neuropeptides and nerve growth factors induce in vivo neurogenic inflammation.Neuropsychiatric factors may participate in the occurrence of psoriasis through the above pathways.%大量证据表明精神因素如焦虑、紧张、精神应激等可以诱发或加重银屑病,还可以在一定程度上影响银屑病的治疗效果,提示精神因素可能在银屑病发病中起到重要作用.目前关于银屑病精神神经相关发病机制的研究主要体现在以下两方面,一方面精神因素作为应激源,引起下丘脑-垂体-肾上腺皮质轴与交感神经-肾上腺髓质系统两大神经内分泌系统的激活;另一方面神经肽及神经生长因子诱导体内的神经源性炎症反应.精神神经因素可能通过以上途径共同参与银屑病发病.

摘要： 目的 研究侧脑室内注射瘦素对2型糖尿病大鼠阿黑皮素原(POMC)、神经肽Agouti相关蛋白(AGRP)及空腹血糖的影响.方法 选取雄性8周龄SD 2型糖尿病大鼠80只,分为侧脑室内注射瘦素组和侧脑室内注射赋形剂(vehicle)对照组,各40岁.对瘦素注射组大鼠进行侧脑室5 μL/kg(空腹瘦素水平15 ng/mL)侧脑室瘦素注射,分别以等剂量对对照组进行vehicle侧脑室注射.48 h后进行大鼠空腹血糖监测并使用ELISA分析检测试剂盒对两组大鼠血清标本进行POMC及AGRP滴度测定.结果 注射瘦素组大鼠空腹血糖水平显著低于对照组(P＜0.05),注射瘦素组大鼠血清POMC较对照组表达显著增加(P＜0.05),AGRP表达显著降低(P＜0.05).结论 侧脑室注射瘦素可显著降低2型糖尿病大鼠空腹血糖水平,增加POMC表达,降低AGRP表达.%Objective To study the effect of intracerebroventricular injection of leptin on proopiomelanocortin(POMC) and neuropeptide Agouti related protein (AGRP) and fasting blood glucose (FBG) in rats with type 2 diabetes mellitus (T2DM).Methods Eighty male 8-week-age SD rats with T2DM were selected and divided into two groups:intracerebroventricular injection of leptin group(n=40)and intracerebroventricular injection of vehicle control group(n =40).Intracerebroventricular injection of 5 μL/kg(fasting leptin level 15 ng/mL) leptin was performed in the leptin injection group,and the control group was injected with same amount of vehicle instead.After 48 h,the FBG level was determined,and the levels of POMC and AGRP were detected by the titer method.Results The level of FBG in the leptin injection group was significantly lower than that in the control group(P＜ 0.05),the expression of serum POMC in the leptin injection group was significantly higher than that in control group(P＜0.05),The expression of AGRP in the leptin injection group was significantly decreased than control group(P＜0.05).Conclusion intracerebroventricular injection of leptin can significantly reduce the FBG level in rats with T2DM,increases POMC expression and decreases AGRP associated protein expression.

摘要： Substance P is a eleven amino acid polypeptide,are widely distributed in the nervous system and other peripheral organs and tissues,the G protein coupled receptor neurokinin 1 receptor distributed in the ventral and dorsal nerve of tongue.Substance P is not only a neuropeptide,but also an immunomodulatory factor,mediating neurogenic inflammation,inducing a variety of inflammatory mediators,mediating leukocyte infiltration and participating in the pathological process of respiratory inflammatory diseases.Obstructive sleep apnea syndrome in patients with soft palate,uvula and tongue mucosa due to nerve damage hypopnea syndrome,inflammatory propeptide leads to the increase of pathological changes of neurogenic inflammation,resulting in pharyngeal airway volume decrease or occlusion,leading to increased inspiratory airway resistance in patients with OSAHS when.When the upper airway muscles are innervated by the denervation,there will be a lack of neuromuscular compensation when the upper airway is blocked.These changes may play a role in the pathogenesis of 0SAHS.This review is a review of the relationship between substance P and its receptors and obstructive sleep apnea hypopnea syndrome.%P物质是一种十一氨基酸多肽,广泛地分布于神经系统和其他外周组织器官内,其G蛋白偶联受体神经激肽1受体密集分布于舌下神经腹侧及背侧部.P物质不仅是一种神经肽,也是一种免疫调节因子,介导神经源性炎症、诱导多种炎症介质产生,介导白细胞肺浸润,参与呼吸道炎症性疾病的病理过程.阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者软腭、悬雍垂及舌根黏膜由于神经损伤,炎性前肽的增加导致神经源性炎症的病理变化,造成咽部气道容积减小甚至闭塞,从而导致OSAHS患者吸气时上气道阻力增加.而上气道肌肉由于失神经支配的损害,在上气道发生阻塞时会出现神经肌肉代偿不足.这些变化可能在OSAHS的发病机制中起—定作用.现就P物质及其受体与OSAHS的关系做一综述.

摘要： 目的副交感神经抑制是否影响变应性鼻炎(AR)鼻黏膜Th1/Th2细胞因子及神经肽的表达。方法 24只小鼠随机分成对照组、AR模型组和AR治疗组。检测各组白细胞介素4、干扰素γ,P物质、血管活性肠肽的表达。结果 AR模型组白细胞介素4、P物质、血管活性肠肽表达水平明显高于对照组,AR治疗组上述因子低于AR组。结论抑制胆碱能神经可以缓解AR症状,而且可以调节AR鼻黏膜Th2优势的免疫反应以及神经肽等炎症相关因子的表达。

摘要： 目的 评价神经病理性痛大鼠杏仁核神经肽S(NPS)与脊髓背角5-羟色胺(5-HT)和GABA的关系.方法 清洁级健康雄性SD大鼠80只,体重200～ 260 g,2月龄,采用随机数字表法分为4组(n=20):假手术组(Sham组)、神经病理性痛组(NP组)、NPS低剂量组(L-NPS组)和NPS高剂量组(H-NPS组).采用左侧L5.6脊神经结扎(SNL)法制备神经病理性痛模型.L-NPS组和H-NPS组分别于SNL后3、6、9、12、15和18d时双侧杏仁核注射NPS,L-NPS组每侧10 pmol、H-NPS组每侧100 pmol.于SNL前2d、SNL后1、4、7、11、14、17和21d时测定机械缩足反射阈(MWT)和热缩足潜伏期(TWL).于SNL后7、14和21d时取5只大鼠,采用荧光免疫组化法检测脊髓背角5-HT和GA-BA的表达.结果 与Sham组比较,NP组、L-NPS组和H-NPS组MWT降低,TWL缩短,脊髓背角5-HT和GABA表达下调(P＜0.05);与NP组比较,L-NPS组和H-NPS组MWT升高,TWL延长,脊髓背角5-HT和GABA表达上调(P＜0.05);与L-NPS组比较,H-NPS组MWT升高,TWL延长,脊髓背角5-HT和GABA表达上调(P＜0.05).结论 大鼠神经病理性痛时杏仁核NPS内源性镇痛作用的脊髓机制可能与上调脊髓背角5-HT和GABA的表达有关.%Objective To evaluate the relationship between neuropeptide S (NPS) in the amygdala and 5-hydroxytryptamine (5-HT) and GABA in spinal dorsal horns of rats with neuropathic pain.Methods Eighty pathogen-free healthy male Sprague-Dawley rats,weighing 200-260 g,aged 2 months,were divided into 4 groups (n =20 each) using a random number table:sham operation group (group Sham),neuropathic pain group (group NP),low dose NPS group (group L-NPS) and high dose NPS group (group H-NPS).The neuropathic pain model was established by left L5,6 spinal nerve ligation (SNL) in anesthetized rats.NPS was injected into the bilateral amygdala at 3,6,9,12,15 and 18 days after SNL in LNPS group (10 pmol per side) and H-NPS group (100 pmol per side).The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 2 days before SNL and 1,4,7,11,14,17 and 21 days after SNL.Five rats were selected at 7,14 and 21 days after SNL and sacrificed,and the lumbar segment (L5) of the spinal cord was removed for detection of the expression of 5-HT and GABA in spinal dorsal horns by immunofluorescence histochemistry.Results Compared with group Sham,the MWT was significantly decreased,the TWL was shortened,and the expression of 5-HT and GABA in spinal dorsal horns was down-regulated in NP,L-NPS and H-NPS groups (P＜0.05).Compared with group NP,the MWT was significantly increased,the TWL was prolonged,and the expression of 5-HT and GABA in spinal dorsal horns was up-regulated in L-NPS and H-NPS groups (P＜0.05).Compared with group L-NPS,the MWT was significantly increased,the TWL was prolonged,and the expression of 5-HT and GABA in spinal dorsal horns was up-regulated in group H-NPS (P＜0.05).Conclusion The spinal mechanism of endogenous analgesia induced by NPS in the amygdala may be related to up-regulation of the expression of 5-HT and GABA in spinal dorsal horns of rats with neuropathic pain.

摘要： 目的 探讨成人原发性癫痫患者治疗前与卡马西平(CBZ)、丙戊酸钠(VPA)治疗6个月后血清酰基化ghrelin(AG)和nesfatin-1水平变化的意义.方法 选取2013年2月至2015年2月济宁医学院附属医院神经内科收治的成人原发性癫痫患者,共50例,其中30例为部分性发作继发全面性发作(SGE),20例为原发性全面性发作(PGE).分别给予CBZ、VPA治疗6个月,于治疗前和药物治疗后用酶联免疫吸附法测定血清AG和nesfatin-1水平.结果 SGE组治疗前血清AG水平[(32.67±5.64)ng/L]低于对照组[(42.49±8.24)ng/L](t=2.08,P<0.05),CBZ治疗6个月后AG水平[(54.31±7.91)ng/L]较治疗前增高(t=2.80,P<0.05).PGE组治疗前血清AG水平[(31.56±6.32)ng/L]低于对照组(t=2.09,P<0.05),VPA治疗6个月后血清AG水平[(51.37±7.56)ng/L]较治疗前增高(t=3.22,P<0.05).SGE组治疗前血清nesfatin-1水平[(6.57±0.93)μg/L]高于对照组[(0.66±0.02)μg/L](t=2.18,P<0.05),CBZ治疗6个月后nesfatin-1水平[(2.74±0.56)μg/L]较对照组仍升高(t=2.05,P<0.05).PGE组治疗前血清nesfatin-1水平[(9.04±1.32)μg/L]较对照组升高(t=3.83,P<0.05),VPA治疗6个月后血清nesfatin-1水平[(3.28±0.43)μg/L]较对照组仍升高(t=2.24,P<0.05).结论 血清AG水平高可能有抗癫痫和神经保护作用,nesfatin-1可能作为癫痫诊断的生物标记物.%Objective To study the serum levels of acylated ghrelin(AG)and nesfatin-1 in adult patients with primary epilepsy in the pretreatment period and six months after carbamazepine (CBZ) or valproic acid(VPA) therapy.Methods Fifty adult patients with primary epilepsy [30 with secondary generalized epilepsy (SGE),20 with primary generalized epilepsy (PGE)] and 20 control patients were included in this study.Serum levels of AG and nesfatin-1 were measured in these groups in the pretreatment period and six months after treatment.Results Serum level of AG in control group was (42.49±8.24)ng/L,pretherapy serum level of AG in SGE (32.67±5.64)ng/L was lower than that in control group (t=2.08,P<0.05).Post-CBZ therapy serum level of AG (54.31±7.91)ng/L was higher than that in pretherapy (t=2.80,P<0.05).Pretherapy serum level of AG in PGE (31.56±6.32)ng/L was lower than that in control group(t=2.09,P<0.05),post-VPA therapy serum level of AG (51.37±7.56)ng/L was higher than that in pretherapy(t=3.22,P<0.05).Serum level of nesfatin-1 in control group was (0.66±0.02)μg/L.Pretherapy serum level of nesfatin-1 in SGE [(6.57±0.93)μg/L] was higher than that in control group(t=2.18,P<0.05),post-CBZ therapy serum level of nesfatin-1 [(2.74±0.56)μg/L] was also higher than that in control group(t=2.05,P<0.05).Pretherapy serum level of nesfatin-1 in PGE (9.04±1.32)μg/L was higher than that in control group (t=3.83,P<0.05),post-VPA therapy serum level of nesfatin-1(3.28±0.43)μg/L was also higher than that in control group (t=2.24,P<0.05).Conclusion AG may have protective effects on neurons and have antiepilepsy effects,nesfatin-1 may serve as biomarker for the diagnosis of primary epilepsy.

摘要： 慢性盆腔疼痛是妇科的常见病、多发病,病因复杂,诊断困难,常见疾病有子宫内膜异位症、盆腔炎性疾病、盆腔脏器脱垂、尾骨痛等。疼痛是一种伤害性感受,慢性盆腔疼痛的发生是疼痛神经传导的过程,机械压力和炎症的刺激是慢性盆腔疼痛产生的主要原因,在疼痛的神经传导过程中,神经肽类物质也参与慢性疼痛的调控。

摘要： 目的探讨orexin-B对正常大鼠丘脑底核神经元自发放电及运动行为的影响。方法应用在体电生理细胞外记录的方法观察orexin-B对大鼠丘脑底核神经元自发放电频率的影响,并采用提升躯体摇摆实验(EBST)观察丘脑底核微量注射orexin-B后大鼠运动行为随时间变化。结果大鼠丘脑底核微压力注射orexin-B,神经元放电频率平均升高(96.85±17.42)%(t=10.242,P<0.01),与生理盐水对照组的细胞反应百分数比较差异有极显著性(Z=-4.157,P<0.01)。EBST结果显示,单侧丘脑底核微量注射orexin-B引起大鼠向对侧摇摆,两组在观察的30、45s向对侧偏转的频率比较,差异有显著性(F=80.35,t=13.42、21.54,P<0.01)。结论 Orexin-B可提高正常大鼠丘脑底核神经元兴奋性,提示orexin-B可能通过基底神经节间接通路参与大鼠运动行为调控。

摘要： Objective To explore the value of serum the significance of endotoxin(ET),procalcitonin(PCT) in the differential diagnosis between acute cholangitis and acute cholecystitis.Methods Sixty-one patients were col-lected,including 20 acute cholangitis,21 acute cholecystitis,10 chronic cholangitis and 10 chronic cholecystitis.Serum ET and PCT were detected in all subjects.Results Serum ET and PCT of patients with acute cholangitis were signifi-cantly higher than the acute cholecystitis(t =4.130,P <0.05).Serum ET and PCT of patients with acute biliary tract infection were significantly higher than the chronic biliary tract infection(t =9.629,t =5.365,P <0.05).Conclusion Joint detection of ET and PCT can increase the early diagnosis rate of acute biliary tract infection.ET and PCT are closely related to the degree of biliary tract infection.%目的：探讨内毒素（ET）、降钙素原（PCT）在鉴别急性胆管炎及急性胆囊炎中的价值。方法检测61例患者血清 ET 及 PCT 浓度，其中急性胆管炎组20例，急性胆囊炎组21例，慢性胆管炎组10例，慢性胆囊炎组10例，比较各组间 ET 及 PCT 的血清学浓度差异。结果急性胆管炎患者血清中 ET、PCT 水平较急性胆囊炎组明显升高（t ＝4．130，P ＜0．05）。急性胆道感染较慢性胆道感染患者 ET、PCT 血清学水平明显升高（t ＝9．629， t ＝5．365，均 P ＜0．05）。结论联合检测患者血清 ET、PCT 浓度可提高急性胆道感染早期确诊率，且 ET、PCT与胆道感染炎症程度密切相关。

摘要： 本发明公开了一类阿片和神经肽FF受体的多靶点多肽，是在基于阿片肽Biphalin和NPFF的嵌合肽BN‑9的基础上进行氨基酸替换，获得一系列能够同时激活阿片和NPFF系统多种受体的多靶点多肽。通过体外cAMP功能鉴定、在体镇痛活性以及中枢副作用等药理学活性的鉴定，表明，该类多靶点多肽能同时激活阿片和神经肽FF受体，具有高效的镇痛活性且不会出现镇痛耐受现象，并且在体温、胃肠运动、心血管活性等方面表现出低副作用的优点。因此，该类多靶点多肽在制备临床镇痛药物方面具有很高的应用价值。

摘要： 本发明公开了一类阿片和神经肽FF受体的多靶点多肽，是在基于阿片肽Biphalin和NPFF的嵌合肽BN‑9的基础上进行氨基酸替换，获得一系列能够同时激活阿片和NPFF系统多种受体的多靶点多肽。通过体外cAMP功能鉴定、在体镇痛活性以及中枢副作用等药理学活性的鉴定，表明，该类多靶点多肽能同时激活阿片和神经肽FF受体，具有高效的镇痛活性且不会出现镇痛耐受现象，并且在体温、胃肠运动、心血管活性等方面表现出低副作用的优点。因此，该类多靶点多肽在制备临床镇痛药物方面具有很高的应用价值。

摘要： 本发明涉及一类阿片和神经肽FF受体多靶点分子BN‑9的类似物及其制备方法与应用，即在BN‑9的氨基酸序列中引入含有巯基侧链的半胱氨酸(Cys)或D‑型半胱氨酸(D‑Cys)，体外功能实验结果显示这四个全新的BN‑9类似物均具有阿片和神经肽FF受体的多靶点激动活性，部分类似物的中枢和外周镇痛药效和作用时间均有所提高，并且都能介导无耐受镇痛作用。因此，该类全新的BN‑9类似物可用于制备镇痛药物。

摘要： 本发明一类阿片和神经肽FF受体多靶点分子BN‑9的二硫键环化类似物，即以BN‑9为化学模板引入侧链含巯基结构的氨基酸残基进行多位点替换修饰，并通过环化修饰而获得一系列二硫键环化类似物。本发明还公开了上述阿片和神经肽FF受体多靶点分子BN‑9的二硫键环化类似物的制备方法与应用。这些类似物可同时激活阿片和神经肽FF受体，并且介导高效、无耐受镇痛作用，该类BN‑9的环化类似物的半衰期、血脑屏障穿透能力以及体内镇痛时间相对母体均有大幅的提高。因此，该类BN‑9二硫键环化类似物可用于制备镇痛药物。

摘要： 本发明公开了一类阿片和神经肽FF受体的多靶点多肽，是在基于阿片肽Biphalin和NPFF的嵌合肽BN‑9的基础上进行氨基酸替换，获得一系列能够同时激活阿片和NPFF系统多种受体的多靶点多肽。通过体外cAMP功能鉴定、在体镇痛活性以及中枢副作用等药理学活性的鉴定，表明，该类多靶点多肽能同时激活阿片和神经肽FF受体，具有高效的镇痛活性且不会出现镇痛耐受现象，并且在体温、胃肠运动、心血管活性等方面表现出低副作用的优点。因此，该类多靶点多肽在制备临床镇痛药物方面具有很高的应用价值。

摘要： 本发明公开了一类阿片和神经肽FF受体的多靶点多肽，是在基于阿片肽Biphalin和NPFF的嵌合肽BN‑9的基础上进行氨基酸替换，获得一系列能够同时激活阿片和NPFF系统多种受体的多靶点多肽。通过体外cAMP功能鉴定、在体镇痛活性以及中枢副作用等药理学活性的鉴定，表明，该类多靶点多肽能同时激活阿片和神经肽FF受体，具有高效的镇痛活性且不会出现镇痛耐受现象，并且在体温、胃肠运动、心血管活性等方面表现出低副作用的优点。因此，该类多靶点多肽在制备临床镇痛药物方面具有很高的应用价值。

摘要： 本发明公开了一种阿片和神经肽FF受体的多靶点多肽，是在基于阿片肽Biphalin和NPFF的嵌合肽BN‑9的基础上进行氨基酸替换，获得一系列能够同时激活阿片和NPFF系统多种受体的多靶点多肽。通过体外cAMP功能鉴定、在体镇痛活性以及中枢副作用等药理学活性的鉴定，表明，该类多靶点多肽能同时激活阿片和神经肽FF受体，具有高效的镇痛活性且不会出现镇痛耐受现象，并且在体温、胃肠运动、心血管活性等方面表现出低副作用的优点。因此，该类多靶点多肽在制备临床镇痛药物方面具有很高的应用价值。

摘要： 本发明涉及式(I)的神经肽－2受体激动剂：Y－R

摘要： 本发明设计了一类新型外周限制性的针对阿片受体和神经肽FF受体的多靶点环肽分子或其药学上可接受的盐。即以DN‑9为化学模板，利用氨基酸替换和环化修饰等多肽化学策略对阿片肽和神经肽FF药效团进行结构优化，获得一系列环肽分子。该环肽分子能够同时激活阿片受体和NPFF受体，其镇痛活性、镇痛时长与母体DN‑9分子相比均大幅度提高且镇痛耐受、便秘和成瘾等阿片样副作用都较低。因此，该类多靶点环肽分子或其药学上可接受的盐在制备高效、低副作用的镇痛药物方面具有很高的应用价值。

摘要： 本发明一类阿片和神经肽FF受体多靶点分子BN‑9的二硫键环化类似物，即以BN‑9为化学模板引入侧链含巯基结构的氨基酸残基进行多位点替换修饰，并通过环化修饰而获得一系列二硫键环化类似物。本发明还公开了上述阿片和神经肽FF受体多靶点分子BN‑9的二硫键环化类似物的制备方法与应用。这些类似物可同时激活阿片和神经肽FF受体，并且介导高效、无耐受镇痛作用，该类BN‑9的环化类似物的半衰期、血脑屏障穿透能力以及体内镇痛时间相对母体均有大幅的提高。因此，该类BN‑9二硫键环化类似物可用于制备镇痛药物。