外源性醛固酮负性调控大鼠血浆神经肽Y的相关信号通路

目的探讨醛固酮（Ald）诱导心肌肥大的大鼠模型中,负性调控血浆神经肽Y（NPY）所涉及的信号转导机制。方法健康雄性Wistar大鼠,随机分为3组正常对照组;Ald组皮下注射Ald（18μg/d）14d;环孢素A组皮下注射Ald（18μg/d）,环孢素A（5mg·g-1·d-1）皮下注射14d。测量尾动脉压,取心脏测量左心室质量/体质量（LVW/BW）,用放免方法测定血浆NPY、血管紧张素Ⅱ（AⅡ）、Ald含量。结果Ald组较正常组LVW/BW升高,NPY和AⅡ下降,Ald增加;环孢素A组较醛固酮组LVW/BW降低,NPY、AⅡ和Ald增加。结论外源性醛固酮可通过激活钙调神经磷酸酶信号通路,负性调控大鼠神经肽Y的生成和分泌。     

中医综合减肥法对肥胖症大鼠血浆神经肽Y的影响

目的探讨中医综合疗法对血浆神经肽水平的影响作用。方法将70只SD大鼠随机分成正常对照组、模型对照组、阳性对照组、针灸治疗组、埋线治疗组、中药治疗组、综合治疗组,每组10只。采用营养肥胖造模方法复制肥胖模型大鼠,造模前、后尾静脉取血,放射免疫法检测各组大鼠血浆神经肽含量。结果模型组血浆神经肽水平明显低于正常组（P〈0.05）,综合治疗组体重血浆神经肽水平明显高于模型组（P〈0.01）。结论中医综合疗法的减肥作用机制可能与升高血浆神经肽Y水平有关。     

负荷运动对幼年自发性高血压大鼠血浆神经肽Y的影响

目的　观察在自发性高血压大鼠 (SHR)幼年时即高血压尚未完全形成时血浆NPY的情况以及运动对它的影响 ,从而探讨血浆NPY对遗传性高血压的早期发现有何意义。方法　 6周龄SHR、WKY各 2 8只 ,随机分为静态组、运动组 ,静态组行有创血压测定、血浆NPY测定 ,运动组行游泳负荷运动后行上述指标测定 ,分别比较静态组、WKY、SHR 6min内的平均血压、峰血压、达峰时间、血浆NPY的均数和运动组WKY、SHR的上述指标的均数。结果　静态组WKY、SHR平均血压、峰血压有差异 ,血浆NPY无明显差异 ,而运动组WKY、SHR平均血压、峰血压无差异 ,血浆NPY却有明显差异 (P <0 0 5 )。结论　幼年SHR运动后血浆NPY释放明显增多 ,此可能为遗传性高血压发生、发展的原因之一 ,对人类遗传性高血压的早期发现、早期干预具有意义     

急性脑血管病患者血浆神经肽Y测定

神经肽Y(NPY)是由36个氨基酸残基组成的神经活性肽,广泛存在于神经系统组织内.本文通过对78例急性脑血管病患者血浆NPY进行测定,探讨神经肽Y在急性脑血管病中的临床意义.     

神经肽Y对心血管疾病影响的研究进展

神经肽Y（neuropeptideY，NPY）是36个氨基酸残基多肽，属胰多肽家族。Tatemoto等于1982年首先从猪脑中提取了NPY并报道了NPY的序列。大量的研究证明NPY广泛分布在哺乳动物的中枢和周围神经系统中，并与该部位神经元中的其他神经递质共存。NPY参与多种生物学效应，包括消化、循环系统和神经内分泌系统的调节以及抗焦虑作用。近年来大量的研究表明NPY通过多种途径对心血管活动起重要的调节作用，并参与了多种心血管疾病的发生、发展过程，现就其研究进展综述如下。     

脑卒中患者血浆神经肽Y浓度变化及临床意义

为探讨脑卒中患者血浆神经肽Y（NPY）浓度变化及意义。对63例脑卒中患者（脑出血组36例，脑梗死组37例）进行了血浆NPY测定。结果显示，与正常对照组比较，脑卒中患者病后2－4天血浆NPY浓度增高明显（P＜0．01）－，14－16天基本恢复正常（P＞0．05）。脑出血组病情轻，中，重型患者的NPY浓度有明显差异（P＜0．05），而脑梗死组无明显差异（P＞0．05）。认为血浆NPY浓度变化可作为判断脑出血患者病情和预后的参考指标。     

肝硬化患者检测血浆神经肽Y的临床意义

研究肝硬化患者血浆神经肽Y的变化及其临床意义。肝硬化患者 6 4例。男 40例 ,女 2 4例 ,平均年龄 45岁± 2 3岁。其中乙型肝炎性肝硬化 5 7例 ,丙型肝炎性肝硬化 2例 ,酒精性肝硬化 4例 ,心源性肝硬化 1例 ,伴消化道出血 2 0例 ,腹水 36例 ,肝性脑病 12例和肝肾综合症 4例。按肝功能分级Child分级 :A级 2 8例 ,B级 2 3例 ,C级 13例。采用RIA法检测空腹血浆NPY水平 ,并与 40例 (男 2 6例 ,女 14例 ,平均年龄 42岁± 2 0岁 )健康人作对照。肝硬化A级患者血浆NPY含量 (12 1 6± 2 8 9) pg/ml低于健康对照组 (142 3± 40 5 ) pg/ml(P <0 0 5 )。肝硬化B级 (6 3 4± 2 4 8) pg/ml,C级 (4 5 6± 2 1 7) pg/ml患者血清NPY含量显著低于健康对照组及肝硬化A级患者 (P <0 0 1)。肝硬化患者血浆NPY含量显著低下 ,并随肝功能损害程度加重而下降更多 ,提示NPY可能参与了肝损害的病理过程 ,并与肝功能分级有关。     

神经肽Y与高血压

神经肽Ｙ（ＮＰＹ）是一种神经多肽,１９８２年由Ｔａｔｅｍｏｔｏｋ在猪脑发现,研究发现ＮＰＹ与原发性高血压及部分继发性高血压有关,ＮＰＹ可通过多种途径参与高血压的发病,极可能是一个独立的致高血压因子。对ＮＰＹ致病原理的进一步探讨有助于进一步了解高血压的发病机制,并为ＮＰＹ受体拮抗药物的开发应用提供理论依据。     

重度高血压降压治疗前后血浆神经肽Y的变化

目的观察重度高血压患者降压治疗前后血浆神经肽Ｙ（ＮＰＹ）浓度的变化,探讨血压变化与血浆ＮＰＹ浓度变化的关系。方法用放射免疫法测定１５例重度原发性高血压患者降压治疗前后的血浆ＮＰＹ浓度。１５例临界轻型高血压患者和１５例健康献血员分别作为高血压和正常血压对照组。结果重度高血压患者治疗前后的血浆ＮＰＹ浓度均高于正常,降压治疗后血浆ＮＰＹ浓度下降４９．８％（Ｐ＜０．００１）,此时的血压水平与临界轻型高血压相近,而血浆ＮＰＹ浓度较高（Ｐ＜０．０１）。治疗前后的血浆ＮＰＹ浓度与舒张压或收缩压均无直线相关性。结论血浆ＮＰＹ的变化可能是血压急剧变化的结果,而不是其原因。     

冠心病患者血浆神经肽Y水平的临床观察

选择符合WHO诊断标准的急性心肌梗塞(AMI)21例,心绞痛(AP)19例,应用放射免疫法动态观察血浆神经肽Y(NPY)含量变化,并以21例正常人作对照.结果显示:对照组NPY水平为 75.1±30.4Pg/ml,AMI组发病第1天NPY含量达峰值,为136.7±66.5pg/ml,显著高于正常组(P<0.05).发病第3天开始下降,第1周末趋于正常,为77.4±48.4pg/ml,与正常组比较无显著差异.AP组于心绞痛发作期NPY含量为159.3±98.5pg/ml,亦显著高于对照组(P<0.05);经治疗2周症状缓解后复查血浆NPY含量下降至118.9±54.3pg/ml,前后比较有显著差异(P<0.05).冠心病伴高血压者血浆NPY含量为186.9±103.1Pg/ml,显著高于不伴高血压者(111.7±45.5pg/ml,P<0.01);既往有吸烟史的冠心病患者,血浆NPY含量为181.8±193.1pg/ml,显著高于无吸烟史者(122.0±65.6pg/ml,P<0.05).提示:NPY水平在冠心病发病初期显著升高,其升高可能由于心肌缺血急性期交感神经兴奋性提高、释放活性增强所致,而高血压及吸烟可能也产生对NPY释放的影响.NPY参与了冠心病的发病机理及病理生理过程.     

环孢素A调控肾性高血压大鼠血浆神经肽Y的作用机制

目的:探讨一肾一夹肾性高血压大鼠模型中,血浆神经肽Y（NPY）含量变化调控机制。方法:健康雄性Wistar大鼠,随机分为3组。①假手术组;②高血压组:通过一肾一夹法复制肾性高血压大鼠;③环孢素A组:环孢素A（CsA）5mg·kg-1·d-1皮下注射;全部大鼠均在实验14d后,测量尾动脉压,取心脏测量左心室质量/体质量（LVW/BW）,用放免方法测定血浆NPY、血管紧张素Ⅱ（AⅡ）、醛固酮（Ald）含量。结果:高血压组较假手术组BP、LVW/BW升高,NPY下降,Ald增加;CsA组较高血压组LVW/BW降低,NPY增加,Ald无显著变化。结论:Ald对血浆NPY水平的负性调控,是通过CaN信号转导通路介导而发生的。     

Genetic studies of neuropeptide Y and neuropeptide Y receptors Y1 and Y5 regions in morbid obesity

Summary Synthesis and release of neuropeptide Y (NPY) are both regulated by leptin binding to its hypothalamic receptor mediating some of the effects of leptin on food intake. Moreover, NPY administration is a powerful stimulant of feeding behaviour. Thus, we investigated the potential implication of NPY, NPY-Y1 and -Y5 subtype receptors [rNPY-Y1/-Y5] in the development of human obesity. Two complementary genetic approaches were used: 1) linkage analyses between obesity and polymorphic markers located nearby NPY and rNPY-Y1/-Y5 genes (respectively on chromosomes 7p15.1 and 4q[31.3–32]) in 93 French Caucasian morbidly obese families; 2) single strand conformation polymorphism (SSCP) scanning of the coding region of the NPY and rNPY-Y1 genes performed in 50 unrelated obese patients ascertained on the basis of a body mass index of 27 kg/m² or more and a family history of obesity. No evidence of linkage between morbid obesity or obesity-related quantitative traits and NPY and rNPY-Y1/Y5 regions was found in this population. Moreover, SSCP scanning revealed no mutation in the coding region of NPY and rNPY-Y1 genes among obese subjects. These results suggest that NPY and NPY-Y1/Y5 receptors are unlikely to be implicated in the development of human morbid obesity, at least in the French Caucasian population. [Diabetologia (1997) 40: 671–675] Received: 27 December 1996 and in revised form: 26 February 1997     

脑出血大鼠血浆神经肽Y及血清肌酸磷酸激酶MB型的变化

目的　观察实验性脑出血条件下血浆神经肽Y(NPY)及肌酸磷酸激酶MB型 (CK MB)含量的动态变化 ,以探讨脑心综合征的发生机制。方法　采用胶原酶和肝素联合注入尾状核方法建立大鼠脑出血模型 ,测定出血前、出血后 30min、6、12、2 4、4 8及 72h血浆NPY活性及血清CK MB变化。采用放射免疫法测定血浆NPY的变化 ,采用酶反应速率法测定血清CK MB的变化。结果　大鼠脑内血肿开始形成的 6h血浆NPY活性、血清CK MB均较术前水平及对照组显著升高 (P <0 .0 5 ) ,并以脑出血 2 4h血肿高峰期时最为显著 (P <0 .0 1) ,随后逐渐下降 ,72h仍高于术前水平及对照组 (P <0 .0 5 )。结论　脑出血时常伴有血清CK MB改变 ,外周NPY含量升高可能参与脑心综合征的发生发展。     

老年单纯收缩期高血压患者血浆中神经肽Y浓度的变化

目的　观察老年单纯收缩期高血压 (ISH)患者血浆神经肽Y(NPY)浓度的变化 ,并探讨其临床意义。方法　采用放射免疫法测定 40例ISH患者血浆NPY浓度 ,其中 30例应用彩色多普勒超声心动图仪测定左室射血分数。结果　 (1)ISH患者NPY浓度较正常对照组明显升高 (P <0 .0 1)。且NPY的浓度与收缩压增高的幅度呈正相关。(2 )ISH患者血浆NPY浓度 1级最低 ,2级居中 ,3级最高 ,各级之间差异有显著性意义 (F =6 7.5 8,P <0 .0 1)。(3)血浆NPY浓度随心功能损害程度加重而上升 (F=5 9.6 8,P <0 .0 1)。结论　NPY可能参与高血压的发生和发展 ,并与病情有关。检测血浆NPY浓度可作为判断ISH患者病情的指标     

An immunohistochemical study of neuropeptide Y in the bovine pineal gland

Abstract: An immunohistochemical study of the bovine pineal gland was performed using rabbit polyclonal antibodies raised against neuropeptide Y (NPY) or against the C-terminal flanking peptide of proNPY (CPON). A large number of NPY/CPON-immunoreactive (IR) nerve fibers were demonstrated throughout bovine pineal gland. The IR-fibers were located in the capsule of the gland, usually piercing into the gland together with blood vessels. In the gland itself, the fibers wen also located intraparenchymally between the pinealocytes. Within the rostral and caudal areas of the pineal stalk, NPY-IR fibers were also observed, and these fibers could be followed not only into the gland bul also to the habenular and posterior commissures. The morphological localization of the NPY-IR nerve fibers in the bovine pineal gland indicate that the majority of fibers originate from the superior cervical ganglion. However, some fibers probably originate from the brain itself.     

高血压病患者血浆神经肽Y水平改变的比较研究

目的　探讨高血压病患者血浆神经肽Y(neu ropeptideY ,NPY)、肾上腺素 (adrenaline)水平的改变及苯那普利、缬沙坦的干预影响。方法　采用同位素放射免疫分析法 ,对 80例高血压患者和 30例正常健康人进行血浆NPY、肾上腺素水平测定 ,高血压患者分成两组 ,分别给予苯那普利、缬沙坦治疗 4w ,测定服药后该指标的变化。结果　高血压患者血浆NPY含量为 (15 1 39± 2 5 32 )pg/ml明显高于正常对照组 (10 1± 10 4 )pg/ml,肾上腺素含量为 (10 3 12±16 2 5 )pg/ml明显高于正常对照组 70 4 5pg/ml ;药物治疗后血浆NPY、肾上腺素较治疗前明显下降 ;但两组药物干预比较无明显差异。结论　高血压患者血浆NPY、肾上腺素水平增高 ,存在神经内分泌的激活 ;应用血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体拮抗剂治疗后可使血浆NPY和肾上腺素水平下降 ,这可能是苯那普利和缬沙坦的降压机制之一。     

Presence,distribution, and pharmacological effects of neuropeptide Y in mammalian gastrointestinal tract

The quantitative distribution of neuropeptide Y (NPY) immunoreactivity has been determined along the length of the gastrointestinal tract in three mammalian species; rat, pig, and guinea pig. The peptide was shown to be present in all regions studied and in all three species. Exceptionally high concentrations were found in the region of the lower esophageal sphincter. Pretreatment of rats with 6-hydroxydopamine depleted NPY concentrations by 30–40%, indicating that NPY is colocalized in part with adrenergic nerves. Characterization of the NPY immunoreactivity by high-pressure liquid chromatography revealed a single major peak. NPY immunoreactivity derived from rat extracts eluted consistently earlier from the column than synthetic porcine standard, indicating minor species differences. Pharmacological studies using longitudinal muscle from guinea pig terminal ileum demonstrated that NPY caused a dose-dependent inhibition of the electrically stimulated, neurally mediated contraction of longitudinal smooth muscle. This suggested that NPY may act presynaptically to inhibit cholinergic transmission. The effects of various NPY fragments were also tested on the same preparation. The C-terminal fragments were active but were considerably less potent than NPY, while the free acid form of NPY and N-terminal fragment (1–19) were completely inactive. Thus, this study has demonstrated the presence of NPY in the gastrointestinal tract of various species, particularly within the lower esophageal sphincter. The pharmacological actions of the peptide suggest a role in the control of nonvascular smooth muscle tone.     

Plasma chromogranin A + B,neuropeptide Y and catecholamines in pheochromocytoma patients

Abstract. Plasma levels of chromogranin A + B, neuropeptide Y and catecholamines were analysed before, during and after surgery in seven patients with pheochromocytoma. The aim of the study was to determine the diagnostic sensitivity of these plasma amines and peptides, and to investigate their peroperative fluctuations. Chromogranin A + B in plasma was increased preoperatively in all patients, showed no significant increase during surgery, and normalized postoperatively. Neuropeptide Y, which alone can induce hypertension, was present in high levels in plasma from three patients preoperatively, increased further in four patients during surgery, and was postoperatively low in all patients. Fractionated plasma catecholamines were increased in five patients before surgery, increased in all patients during tumour dissection, and normalized postoperatively. It may be concluded that plasma chromogranin A + B exhibited as high a sensitivity for pheochromocytoma as fractionated urinary catecholamines in the patients studied.