降钙素基因相关肽的血管生物学功能多样性

降钙素基因相关肽是由辣椒素敏感的感觉神经末梢释放的一种生物活性多肽,广泛分布于神经及心血管系统。在心血管系统,降钙素基因相关肽生物活性具有多样性,如强大的舒血管作用、抑制平滑肌细胞增殖和内皮细胞凋亡,也能促进细胞分化增殖,参与血管新生。这种功能的多样性与维持机体的心血管系统功能有密切关系。     

降钙素基因相关肽通过ERK1/2信号通路对角质形成细胞增殖的影响

目的： 研究降钙素基因相关肽（CGRP）对角质形成细胞增殖活性的影响，并探讨其可能涉及的信号转导通路。方法： ①胸腺嘧啶掺入法（［3H］-TdR）观察CGRP诱导的角质形成细胞株HaCaT细胞增殖，及CGRP受体拮抗剂CGRP8-37、细胞外信号调节激酶ERK1/2特异性抑制剂PD98059对CGRP诱导的增殖活性的影响；②免疫印迹技术观察CGRP诱导后ERK1/2的磷酸化，及CGRP8-37、PD98059对ERK1/2磷酸化的影响。结果： ①CGRP在一定范围内可剂量依赖性地诱导HaCaT细胞增殖，该作用可被CGRP8-37和 PD98059阻断；②CGRP可时间依赖性地诱导HaCaT细胞ERK1/2的磷酸化，CGRP8-37和PD98059可减弱其作用。结论： CGRP可诱导HaCaT细胞增殖，CGRP受体及其相关的ERK1/2信号通路参与其调控机制。     

降钙素基因相关肽与脑血管病

降钙素基因相关肽 (CGRP)是人类利用基因重组技术发现的第一个活性多肽 ,具有多种生理功能 ,其药理作用已受到广泛重视。本文就 CGRP在神经系统的分布、扩血管作用、神经保护作用及其与部分脑血管病的关系方面进行了综述     

内皮素及降钙素基因相关肽对儿童哮喘发病的作用及其与心功能的关系

目的：探讨内皮素（ET）及降钙素基因相关肽（CGRP）在儿童哮喘发病中的作用及二者与心功能的关系。方法：用放射免疫分析法对34例哮喘急性发作期（Ⅰ组）、20例缓解期（Ⅱ组）及34例N组血浆ET及CGRP测定,并同期应用M型及二维超声心动图测定哮喘儿童的左、右心收缩及舒张功能,组间比较单因素相关分析。结果：Ⅰ组ET含量显著高于Ⅱ组及N组,Ⅱ期ET含量显著高于N组,Ⅰ组CGRP含量较Ⅱ组及N组显著降低,Ⅱ组血浆CGRP含量较N组显著降低;Ⅰ组左、右室收缩功能指标异常,而舒张功能指标均正常;ET及CGRP与发作期左、右心收缩功能呈低、中度相关。结论：血浆ET及CGRP参与了哮喘的发病过程;ET及CGRP与哮喘发作期左、右心收缩功能异常有一定的关系。     

降钙素基因相关肽对脑缺血大鼠脑血流的影响

大鼠侧脑室注入降钙素基因相关肽（ＣＧＲＰ）或等体积甘露醇为对照，用非损伤阻抗法测定一侧颈总动脉结扎后ＣＧＲＰ对脑血流的影响。结果表明，一侧颈总动脉结扎后，脑血流量降低３４％，此时侧脑室给予ＣＧＲＰ即刻使脑血流图波幅增加，５分钟时达高峰，比注药前平均增加６５％，与甘露醇对照相比差别非常显著（Ｐ＜０．０１），４０分钟时作用开始减弱，１００分钟后作用消失。与颈总动脉结扎前相比，在脑血供不足时，ＣＧＲＰ增     

降钙素基因相关肽放射免疫分析的建立

本文采用皮下、腹腔内联合免疫方法获得抗降钙素基因相关肽（CGRP）抗体。利用Iedogen125I标记CGRP，经高效液相色谱（HPLC）分离纯化，建立了CGRP放射免疫分析（RIA）测定范围20－1200pg／mL，批内CV7％，批间CV12％，上常人血浆含量为50.6±24．5pg／mL（n＝25）。初步用于临床，砚察了CGRP与内皮素（ET）在高血压，十二指肠疾病中的相互关系，所得结果与正常对照组差异显著。     

血浆内皮素与降钙素基因相关肽发迹在高血压病中的意义

用特异性放射免疫分析法测定５０例原发性高血压 患者和３２名正常人的血浆内皮素和降钙素基因相关肽水平，结果显示：ＥＨ患者ＥＴ的水平明显高于对照组，且有左室重塑组明显高于无左室重塑组。     

降钙素基因相关肽对大鼠血糖及血糖调节激素的影响

基于外周给与CGRP能使血糖升高,胰岛素分泌下降,本实验目的在于研究CCRP是否参与血糖浓度的调节及其可能机理。结果表明:静脉灌注CGRP在常态下能使血糖升高,而不影响胰岛素的浓度,在高血糖刺激下CGRP具抑制胰岛素分泌的功能;静脉灌注CGRP对糖耐量曲线有明显影响;脑室注射CGRP可使血糖明显降低。本实验提示CGRP有可能与糖尿病的发生发展有一定关系。     

胰升糖素样肽1对肥胖大鼠肝脏组织中Sesn2/AMPK/mTOR信号通路的干预效应

目的:研究胰升糖素样肽1受体激动剂利拉鲁肽对肥胖大鼠肝脏组织Sesn2/AMPK/mTOR信号通路的影响。方法:雄性SD大鼠随机分为正常饮食组(NC组)与高脂饮食组(HF组),喂养12周后,每组取5只评估肥胖大鼠模型建立。HF组再随机分为HF组、低剂量利拉鲁肽组(LG组)、中剂量利拉鲁肽组(MG组)与高剂量利拉鲁肽组(HG组),各组分别给予生理盐水及不同剂量利拉鲁肽(50、100和200μg/kg,皮下注射,每天2次) 4周。16周时测定体重及附睾脂肪指数;取大鼠肝脏组织HE染色观察肝脏脂肪变性情况; Western blot法检测肝脏组织中Sesn2、AMPK、p-AMPK、mTOR和p-mTOR的蛋白水平。结果:HF组大鼠的体重明显高于NC组(P 0. 01)。HF组肝脏细胞出现脂肪变性。与NC组相比,HF组的Sesn2蛋白水平明显降低(P 0. 01),p-AMPK/AMPK水平明显降低(P 0. 01),而p-mTOR/mTOR水平与NC组相比差异没有统计学显著性。利拉鲁肽干预4周后,药物处理组大鼠体重明显低于HF组(P 0. 01),MG与HG组大鼠的附睾脂肪指数较HF组降低(P 0. 01),肝组织脂肪变性较HF组减轻; HG组的Sesn2蛋白水平明显高于HF组(P 0. 01),MG与HG组的p-AMPK/AMPK水平较HF组明显升高(P 0. 01),LG组、MG与HG组p-mTOR/mTOR水平较HF组明显降低(P 0. 01)。结论:胰升糖素样肽1受体激动剂可能通过Sesn2/AMPK/mTOR信号通路影响机体能量代谢,改善肥胖状态。     

BMP2活性多肽/PLGA复合物植入异位成骨的实验研究

目的用动物实验的方法评价自行研制合成的BMP2活性多肽生物因子与可降解PLGA复合物的异位诱导成骨能力。方法实验分3组。A组：BMP2活性多肽／PLGA复合物组；B组：单纯PLGA组；C组：明胶海绵组。分别于Wistar大鼠背部两侧骶棘肌下包埋植入。术后1、4、8和12周取材。经组织学观察和CT三维成像比较成骨情况，western blot检测Ⅰ型胶原及骨桥蛋白的蛋白表达，了解异位成骨的情况。结果植入块周围初期均表现为急性炎症反应，后期均为淋巴细胞、巨噬细胞浸润为主的非特异性炎症反应。A组植入4周时植入区有软骨生成，8周时有活跃的成骨细胞出现，并有非编织骨结构。12周可见大量新骨形成，有典型的骨小梁新生血管结构。B组和C组12周时仅见纤维组织形成，未见成骨。结论人工合成的BMP2活性多肽体内能启动软骨化骨过程，具有较强的异位诱导成骨能力。有与天然BMP2类似的骨诱导活性，具有广阔的应用前景。     

Hydra peptide morphogen activates Na/H exchange in human erythrocytes

Central Research Laboratory, Khabarovsk Medical Institute. Department of General Pathology and Pathological Physiology, Central Postgraduate Medical Institute, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR I. P. Ashmarin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 111, pp. 586–587, June, 1991.     

Formyl peptide receptor 2 and heart disease

Formyl peptide receptor type 2 (FPR2) regulates the initiation and resolution phases of the inflammatory response. In the setting of heart injury and disease, dysregulated inflammation can potentiate maladaptive healing and pathological remodeling of the heart leading to cardiac dysfunction and failure. The potential to regulate and resolve adverse inflammation is postulated to improve outcome in the setting of heart disease. This review covers emerging concepts on the role of FPR2 in heart disease and strategies to activate pro-resolution processes to limit disease progression. We summarize key preclinical studies that support use of FPR2 agonists in heart disease. Finally, we briefly discuss the status of FPR2 agonists under evaluation in the clinic.     

Altered influenza virus haemagglutinin (HA)-derived peptide is potent therapy for CIA by inducing Th1 to Th2 shift

There has been an increase in interest in the use of altered peptides as antigen-specific therapeutic agents in autoimmune diseases. Here we investigated the inhibitory effect and possible mechanism of an altered influenza virus haemagglutinin (HA)-derived peptide in collagen-induced arthritis (CIA). CIA was induced in DBA/1 mice by immunisation with type II collagen (CII). Altered HA308-317, wild-type HA308-317 or irrelevant peptide was administered intranasally beginning from arthritis onset. Clinical and histological scores were assessed, and cytokine levels in the serum or supernatants from splenocytes were determined. The percentages of Th1 and Th2 cells in response to different peptides were analysed by FACS both in vivo and in vitro. Our results showed that intranasal administration of altered HA308-317 peptide significantly ameliorated CIA. The therapeutic effect of altered HA308-317 peptide was associated with a substantial decrease in production of interferon (IFN)-γ, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, anti-CII IgG, IgG1 and IgG2a antibodies, and an markedly increase in production of IL-10 and IL-4 in serum or supernatants from splenocytes treated with altered HA308-317 peptide. The percentage of Th2 (CD4(+)IL-4(+)) cells was upregulated significantly by altered HA308-317 peptide with a decreased percentage of Th1 (T helper 1; CD4(+)INF-γ(+)) cells both in vivo and in vitro. These findings suggest that altered HA308-317 peptide might be a promising candidate for rheumatoid arthritis (RA) treatment.     

应用小肽融合蛋白免疫诱导抗HER-2体液免疫反应

目的应用HER-2 B细胞表位模拟小肽Mut与Hsc70的融合蛋白诱导抗小肽和抗HER-2的体液免疫反应。方法将Hsc70和Mut小肽序列定向插入pQE40载体中,构建pQE40-Hsc70-Mut原核表达质粒,并诱导表达、纯化融合蛋白Hsc70-Mut。常规免疫Balb/c小鼠,应用ELISA、Western blot检测小鼠血清中抗小肽Mut和抗HER-2的体液免疫反应。结果成功构建了pQE40-Hsc70-Mut原核表达质粒,Hsc70-Mut融合蛋白在大肠杆菌SG13009能够实现可溶性表达,应用Ni-NTA纯化可得到纯度>90%的融合蛋白;Hsc70-Mut免疫小鼠可产生抗Mut小肽的免疫反应,部分小鼠同时可产生抗HER-2的体液免疫反应。结论 Hsc70-Mut融合蛋白免疫小鼠可产生抗小肽和抗HER-2的体液免疫反应,为HER-2疫苗的研制奠定了一定基础,同时应用小肽融合蛋白免疫也为小肽免疫提供了一种新的免疫策略。     

Localization of the bronchodilator effect induced by type A natriuretic peptide in asthmatic subjects

Type A natriuretic peptide (CDD/ANP99-126) in its circulating form was analyzed with respect to the localization of its bronchodilating effects in asthmatic subjects in vivo. The intravenous infusion of 5.7, 11.4, and 17.1 pmol kg^–1 min^– CDD/ANP-99-126 caused a significant bronchodilation of both central and peripheral airways. While the localization of the bronchodilating effects was similar to ₂-agonists, an improvement in lung function parameters comparable to these substances was not observed. But other members of the natriuretic peptide family may reveal a stronger bronchodilating potency.Abbreviations FEV forced expiratory volume in 1 s - FVC forced vital capacity - PEF peak expiratory flow - MEF₇₅, MEF₅₀, MEF₂₅ maximal expiratory flow at 75%, 50%, 25% of forced vital capacity Correspondence to: T. Edge