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1.
肺内调节肽对兔支气管上皮细胞分泌白介素的影响   总被引:10,自引:3,他引:7  
Tan YR  Qin XQ  Guan CX  Zhang CQ  Xiang Y  Ren YH 《生理学报》2002,54(2):107-110
为探讨肺内调节肽对气管上皮细胞(brochial epithelial cells,BECs)分泌功能的影响,实验观察了兔BECs在未受应激与臭氧应激两种条件下白细胞介素(interleukin,ILs)的分泌。结果发现:血管活性肠肽(vasoac-tive intestinal peptide,VIP)以未受应激BECs存在抑制作用,并使用臭氧应激BECs分泌ILs下降;表皮生长因子(epi-dermal growth factor,EGF)使未受应激BECs IL-1、IL-8分泌增加,使臭氧应激的BECs ILs分泌降低;内皮素-1(endothelin-1,ET-1)、降钙素基因相关肽(calctionin gene-related peptide,CGRP)可使未受应激的BECs分泌ILs增加,CGRP还可使臭氧应激的BECs ILs分泌增加。结果提示:肺内调节肽可调控BECs ILs的分泌,在调控气道炎症损伤信号传递方面具有一定的作用。  相似文献   

2.
Tan YR  Qin XQ  Guan CX  Zhang CQ  Luo ZQ  Sun XH 《生理学报》2003,55(2):121-127
细胞间粘附分子—1(ICAM—1)是介导细胞与细胞之间粘附的重要生物分子;核因子—κB(NF—κB)是体内普遍存在、能迅速对刺激产生反应的重要核转录因子。越来越多的证据显示,ICAM—1表达与NF—κB激活是炎症反应的重要步骤。我们应用免疫组化、RT—PCR、凝胶阻滞电泳(EMSA)等多种实验方法,观察了肺内调节肽对支气管上皮细胞ICAM—1表达及NF—κB活性的影响,以及NF—κB抑制剂MG—132对ICAM—1表达的影响。实验结果发现,VIP、EGF可使臭氧应激BECS的ICAM—1表达降低;ET—1、CGRP可使未受应激BECs的ICAM—1表达增加。NF—κB抑制剂MG—132可阻断O3、ET—1、CGRP引起的ICAM—1表达,提示NF—κB在调控ICAM—1表达中起重要作用。EMSA结果显示,BECs中NF—κB在臭氧应激下反复激活,CGRP与ET—1可促进NF—κB的激活;VIP与EGF可抑制臭氧应激的BECs中NF—κB的激活。以上结果说明,VIP、EGF可通过下调ICAM—1转录及NF—κB激活减轻炎症反应,而ET—1、CGRP可通过上调ICAM—1转录及NF—κB激活、加大炎症反应。ICAM—1与NF—κB的持续表达和反复激活是炎症持续加重发展的重要因素。  相似文献   

3.
4.
Ren YH  Qin XQ  Guan CX  Luo ZQ  Zhang CQ  Sun XH 《生理学报》2004,56(2):137-146
为探讨内源性神经肽在气道高反应性形成中的作用,我们以臭氧应激损伤动物气道上皮细胞,建立气道高反应性动物模型,并观察臭氧应激不同时间肺内血管活性肠肽(vasoactive intestinal peptide,VIP)、降钙素基因相关肽(calcitonin gene-related CGRP)含量变化以及VIP受体(VIPR1)、CGRP受体(GRPR1)mRNA在肺内表达、分布的改变。实验观察到,臭氧应激组动物吸入乙酰甲胆碱后气道阻力高于正常对照组,肺内呈现明显的炎症改变。随臭氧应激时间延长,肺组织匀浆中VIP、CGRP浓度呈先增高后降低的双向改变,CGRP达峰值时间早于VIP。VIPR1、CGRPR1 mRNA表达亦经历了双向过程,VIPR1峰值持续时间长于CGRPR1。在无应激对照组动物,肺间质、支气管上皮细胞、血管内皮细胞、平滑肌细胞均有VIPR1、CGRPR1 mRNA表达。随应激时间的延长,阳性细胞呈斑片状集中于气管、血管周围,染色强度增加,至臭氧应激第8天,阳性染色细胞减少。因此我们推测,臭氧应激可以诱导动物气道高反应性的形成。在炎症的早期,以CGRP的作用为主,与肺损伤早期炎症信号的传递有关,以清除刺激原、及时终止致病原的作用;炎症后期以保护机体、促进修复、减轻损伤为主,VIP发挥主要作用。  相似文献   

5.
血管活性肠肽对支气管上皮细胞趋化迁移的影响及机制   总被引:2,自引:0,他引:2  
Guan CX  Zhang CQ  Qin XQ  Luo ZQ  Zhou FW  Sun XH 《生理学报》2002,54(2):103-106
为探讨肺内神经肽在气道损伤修复中的作用 ,采用blind wellBoydenchamber测定原代培养的支气管上皮细胞 (bronchialepithelialcells,BEC)趋化性 ,观察血管活性肠肽 (vasoactiveintestinalpeptide ,VIP)对BEC趋化迁移的影响及其机制 ,并测定经热应激后BEC分泌VIP及表达VIP受体 (vasoactiveintestinalpeptidereceptor,VIPR)的变化。结果显示 :(1)以胰岛素作为趋化因子所建立的BEC趋化性测定方法稳定 ,重现性好 (r =0 970 3,P <0 0 1) ;(2 )VIP (0 0 0 1~ 1μmol/L)均显示剂量依赖性地增强BEC的趋化迁移 ,其效应可被钙调蛋白阻断剂及蛋白激酶C阻断剂有效地抑制 (P <0 0 1) ;(3) 4 2℃、30min热应激后BEC分泌VIP (P <0 0 1)及表达VIPR明显增加 (P <0 0 5 )。实验表明 :肺内神经肽VIP可增强BEC的趋化迁移 ,其细胞内信号转导途径与钙调蛋白及蛋白激酶C有关。而热应激时VIP及VIPR的高表达进一步提示局部微环境的VIP可能是气道上皮损伤修复网络中的重要分子  相似文献   

6.
为了探讨肺内调节肽对人支气管上皮细胞(human bronchial epithelial cells,HBECs)人类白细胞抗原DR(human leukocyte antigen DR,HLA—DR)、CD80和CD86表达的影响,采用免疫细胞化学技术和流式细胞术检测HBECs在非应激和臭氧应激两种状态下HLA-DR、CD80、CD86的表达。结果显示,HBECs表达HLA—DR,臭氧应激状态下HBECs HLA-DR表达降低(P〈0.05);VIP、P3513和CGRP使非应激和臭氧应激两种状态下的HBECs HLA—DR表达增高(均P〈0.05)。HBECs表达协同刺激分子CD80,臭氧应激状态下CD80表达降低(P〈0.05),VIP对非应激的HBECs的CD80表达无影响,使臭氧应激状态下CD80表达增高(P〈0.05);CGRP使非应激状态下的HBECs的CD80表达降低(P〈0.05),使臭氧应激状态下CD80表达增高(P〈0.05);P3513使非应激状态下CD80表达增高(P〈0.05),可使臭氧应激状态下CD80表达降低(P〈0.05)。在HBECs没有检测到CD86表达,臭氧攻击也不能刺激其表达。上述结果提示,HBECs具备成为抗原递呈细胞的必要条件,肺内调节肽可通过调节HLA—DR和协同刺激分子的表达调节HBECs的抗原递呈作用。  相似文献   

7.
白细胞与内皮细胞的粘附   总被引:1,自引:0,他引:1  
白细胞与内皮细胞相互作用由粘附分子介导.整合素、免疫球蛋白及选择素家族的粘附分子在这两种细胞的粘附中起关键作用.粘附的起始阶段由选择素介导,随后由CD11/CD18复合物与ICAM-1形成更为紧密的结合.多种细胞因子及炎症反应可诱导粘附.抗粘附分子单抗、药物等可抑制粘附.  相似文献   

8.
目的和方法:为验证整合素分子激活对支气管上皮细胞(BEC)的抗氧化性保护作用,本实验用臭氧(O3)攻击培养的兔BEC,测定细胞的^3H释放率、乳酸脱氢酶(LDH)释放活性及脂质过氧化产物丙二醛(MDA)含量,反映细胞损伤程度;观察纤维连接蛋白(Fn)及人工合成的精-甘-天冬氨酸片段(RGD肽)的保护效应。结果:①臭氧攻击使BEC的^3H释放率增高,Fn处理可减少臭氧所致的^3H释放,钙调素抑制剂W7能抑制Fn的这一作用,RGD可减轻臭氧所致的^3H释放;②臭氧攻击后细胞上清液中LDH释放增多,Fn或RGD处理均能降低LDH释放,W7阻断Fn的这一效奕;③臭氧作用后明显提高细胞内MDA含量,Fn或RGD可降低MDA含量;④臭氧攻击使细胞内GSH含量下降,Fn或RGD可增加BEC内GSH的含量;⑤Fn可增强BEC内过氧化氢酶(CAT)活性,但可被W7阻断,RGD则显示有剂量依赖性促进作用。结论:Fn及其特异识别片段与BEC的整合素分子结合后,可减轻臭氧对BEC细胞的损伤,其机理与经钙调素途径上调BEC抗氧化能力有关。  相似文献   

9.
李宏键  徐世莲 《蛇志》2007,19(2):140-142
神经肽(neuropeptide,NP)是在骨折创伤时由感觉神经释放,参与组织细胞增殖、分化的调控[1]。目前发现骨组织中含有的神经肽有降钙素基因相关肽(calcitonin gene-relat-ed peptide,CGRP)、P物质(substance P,SP)、血管活性肠肽(vasoactive intestinal polypeptide,VIP)、神经肽Y(neuropep-tide Y,NPY)和腺苷酸环化酶激活肽(adenylate cyclase acti-vating polypeptide,ACAP)、蛋白基因产物(protein geneproduct 9.5,PGP 9·5)和酪氨酸羟化酶(tyrosine hydroxy-lase,TH)等。其中CGRP、SP、VIP等在骨折愈合中的作用目前已越来越…  相似文献   

10.
目的:检测复合应激大鼠模型阴茎组织中降钙素基因相关肽(CGRP)、血管活性肠肽(VIP)的表达,并观察伊木萨克片对二者表达的影响。方法:选用56只正常雄性SD大鼠,其中10只为正常对照组(N),余46只为造模组,采用富含环境雌激素饲料+寒冷环境的干预条件建立复合性应激大鼠模型(20 w),并随机将其分为模型组(B1)、自然恢复组(B2)和伊木萨克干预组(B3),药物干预2 w后,免疫组化及Western blot方法检测大鼠阴茎组织中CGRP、VIP的表达。结果:①大鼠阴茎组织中CGRP表达:B1、B2组较N组明显减少(P0.05);B3组较B1、B2组明显增多(P0.05)。②大鼠阴茎组织中VIP表达:B1、B2组较N组显著降低(P0.05);B3组较B1、B2组显著升高(P0.05)。结论:复合应激大鼠模型阴茎组织中CGRP、VIP明显减少,伊木萨克片干预可抑制此变化。  相似文献   

11.
Qin XQ 《生理科学进展》1999,30(2):129-132
本工作建立了臭氧对原代培养的兔支气管上皮细胞(BEC)损伤模型,观察到血管活性肠肽(VIP)、表皮生长因子(EGF)、热应激等微环境理化因子可减轻细胞损伤,具有细胞保护作用,其保护机制与提高还原谷胱甘肽(GSH)含量有关,并依赖于蛋白激酶的磷酸化调节及基因转录。BEC细胞在基础情况下有bcl-2基因的低水平表达。VIP和EGF可促进bcl-2基因转录,增强BEC的抗氧化损伤能力。EGF或热应激促进  相似文献   

12.
Previous studies have shown that inflammatory pathologies are mediated by lymphocyte adhesion to endothelium and subsequent transmigration through the endothelial monolayer. Lymphocyte-endothelial adherence is, in part, caused by the leukocyte integrin LFA-1 binding to ICAM-1, its ligand on endothelial cells. Synthetic peptides based on specific amino acid sequences of human ICAM-1 inhibit the adherence of a lymphocytic cell line, Molt-4, to cytokine-stimulated endothelial cells. A total of 26 peptides spanning the extracellular domains of ICAM-1 were evaluated for their inhibitory activity in two cell adhesion assays. Binding of fluorescently labeled Molt-4 cells to TNF-stimulated human umbilical vein endothelial cells was inhibited reproducibly by peptides ICAM1-20, ICAM26-50, ICAM40-64, ICAM132-146, and ICAM345-375. Three overlapping sequences of the peptide ICAM40-64, KELLLPGNNRKVYELSNVQEDSQPM, were synthesized and tested as well, and the sequence KELLLPGNNRKV showed the greatest inhibition. The inhibitory activity of these peptides was confirmed using a second assay, inhibition of aggregation of the Epstein-Barr virus-transformed B-lymphoblast line JY. Polyclonal antibodies were developed in rabbits by immunization with two of the peptides and characterized for their ability to inhibit lymphocyte-endothelial adherence. These studies predict potential sites for interaction of the integrin receptor, LFA-1, with its ligand, ICAM-1. Thus lymphocyte-endothelial interaction, and resulting inflammation, may be partially mediated by the association of ICAM-1 with LFA-1 at the specific molecular locations identified in this study.  相似文献   

13.
Vascular resistance in the mammalian pulmonary circulation is affected by many endogenous agents that influence vascular smooth muscle, right ventricular myocardium, endothelial function, collagen and elastin deposition, and fluid balance. When the balance of these agents is disturbed, e.g. by airway hypoxia from high altitude or pulmonary obstructive disorders, pulmonary hypertension ensues, as characterized by elevated pulmonary artery pressure (P(PA)). Among neuropeptides with local pulmonary artery pressor effects are endothelin-1 (ET-1), angiotensin II (AII), and substance P, and among mitigating peptides are calcitonin gene-related peptide (CGRP), adrenomedullin (ADM), atrial natriuretic peptide (ANP), vasoactive intestinal peptide (VIP) and ET-3. Moreover, somatostatin28 (SOM28) exacerbates, whereas SOM14 decreases P(PA) in hypoxic rats, with lowering and increasing of lung CGRP levels, respectively. Pressure can also be modulated by increasing or decreasing plasma volume (VIP and ANP, respectively), or by induction or suppression of vascular tissue remodeling (ET-1 and CGRP, respectively). Peptide bioavailability and potency can be regulated through hypoxic up- and down- regulation of synthesis or release, activation by converting enzymes (ACE for AII and ECE for ET-1), inactivation by neutral endopeptidase and proteases, or by interaction with nitric oxide (NO). Moreover, altered receptor density and affinity can account for changed peptide efficacy. For example, upregulation of ET(A) receptors and ET-1 synthesis occurs in the hypoxic lung concomitantly with reduced CGRP release. Also, receptor activity modifying protein 2 (RAMP2) has been shown to confer ADM affinity to the pulmonary calcitonin-receptor-like receptor (CRLR). We recently detected the mRNA encoding for RAMP2, CRLR, and the CGRP receptor RDC-1 in rat lung. The search for an effective, lung selective treatment of pulmonary hypertension will likely benefit from exploring the imbalance and restoring the balance between these native modulators of intrapulmonary pressure. For example, blocking of the ET-1 receptor ET(A) and vasodilation by supplemental CGRP delivered i. v. or via airway gene transfer, have proven to be useful experimentally.  相似文献   

14.
Qin XQ  Sun XH  Luo ZQ 《生理学报》1999,51(4):419-424
为探索肺内调节血管活性肠肽(VIP)和表皮生长因子(EGF)抗氧化保护的基因机制,用逆转录聚合酶链式反应(RT-PCR)及Southemblot杂交等方法检测的代培养的兔支气管上皮(BEC)内bcl-2和c-myc基因的表达中加入去甲肾上腺素观察VIP、EGF热应激对这两个基因表达的影响。结果显示:(1)基基础情况下BEC内有bcl-2和c-myc基因的低水平表达;(2)EGF和VIP明显增强bc  相似文献   

15.
The mechanisms by which respiratory syncytial virus (RSV) infection causes airway hyperresponsiveness (AHR) are not fully established. We hypothesized that RSV infection may alter the expression of airway sensory neuropeptides, thereby contributing to the development of altered airway function. BALB/c mice were infected with RSV followed by assessment of airway function, inflammation, and sensory neuropeptide expression. After RSV infection, mice developed significant airway inflammation associated with increased airway resistance to inhaled methacholine and increased tracheal smooth muscle responsiveness to electrical field stimulation. In these animals, substance P expression was markedly increased, whereas calcitonin gene-related peptide (CGRP) expression was decreased in airway tissue. Prophylactic treatment with Sendide, a highly selective antagonist of the neurokinin-1 receptor, or CGRP, but not the CGRP antagonist CGRP(8-37), inhibited the development of airway inflammation and AHR in RSV-infected animals. Therapeutic treatment with CGRP, but not CGRP(8-37) or Sendide, abolished AHR in RSV-infected animals despite increased substance P levels and previously established airway inflammation. These data suggest that RSV-induced airway dysfunction is, at least in part, due to an imbalance in sensory neuropeptide expression in the airways. Restoration of this balance may be beneficial for the treatment of RSV-mediated airway dysfunction.  相似文献   

16.
Wang Y  Zhang M  Tan Y  Xiang Y  Liu H  Qu F  Qin L  Qin X 《Cell biology international》2007,31(12):1495-1500
Airway re-modelling in asthma usually results in an irreversible weakness of pulmonary ventilation, however, its initiating or controlling mechanism remains unclear. In this study, we hypothesize that signal communication between airway epithelial cells and sub-mucosal fibroblast cells may play an important role in the maintenance of structure homeostasis in a physiologic condition and in initiation of airway remodelling in a stressed condition. To test the hypothesis, a co-cultured system of human bronchial epithelial cells (BEC) and human lung fibroblasts (HLF) were designed to observe the effects of BEC, in the normal state or in a BRS-3 activated state, on the proliferation and collagen synthesis of HLF. The results showed that the proliferation activities of both BEC and HLF inhibited each other under the normal state. BRS-3-activated BEC can transform the reciprocal inhibition into promoting effects. The secretion of TGF-beta1 increased and the synthesis of PGE2 decreased from BRS-3-activated BEC, which were correlated with the proliferation and collagen synthesis of HLF. The proliferation activities of HLF were weakened by co-culture with TGF-beta1 antisense oligonucleotides (ASO) treated BEC. It was concluded that, in the normal state, BEC inhibits the activities of fibroblasts through release of PGE2 to maintain the airway homeostasis; however when stressed, for example by BRS-3 activation, BEC promote the activities of fibroblasts mediated by TGF-beta1, thereby facilitating the airway re-modelling.  相似文献   

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