本文選題：血管平滑肌細(xì)胞　切入點(diǎn)：血管活性肽　出處：《河北醫(yī)科大學(xué)》2005年博士論文

【摘要】：血管活性肽是一類調(diào)節(jié)血管平滑肌細(xì)胞(vascular smooth muscle cell,VSMC)舒縮功能、維持血管張力的小分子肽類物質(zhì),多數(shù)以自分泌、旁分泌方式發(fā)揮作用,按其血管效應(yīng)的不同分為縮血管肽和舒血管肽。前者包括血管緊張素I(Iangiotensin II,Ang II)和內(nèi)皮素-1(endothelin-1,ET-1)等,后者包括腎上腺髓質(zhì)素(adrenomedullin,ADM)和心鈉素(atrial natriuretic factor,ANF)等。生理?xiàng)l件下,血管舒-縮活性肽的分泌和生物活性處于動(dòng)態(tài)平衡,以保證血管張力的穩(wěn)態(tài)。不同種類的活性肽之間存在著復(fù)雜的正反饋或負(fù)反饋調(diào)節(jié),由此構(gòu)成一個(gè)精細(xì)、嚴(yán)密的血管張力調(diào)控網(wǎng)絡(luò)。由于大多數(shù)縮血管活性肽具有強(qiáng)烈的促進(jìn)VSMC 肥大、增殖、遷移的活性,其功能的亢進(jìn)常常是多種血管重塑性疾病的主要誘因。而舒血管活性肽則具有相反的作用。因此,研究血管活性肽之間形成的復(fù)雜網(wǎng)絡(luò),闡明該網(wǎng)絡(luò)對(duì)血管功能的調(diào)節(jié)機(jī)制,將有利于深層次了解血管活性肽系統(tǒng)的生理功能和在心血管疾病發(fā)生發(fā)展中的病理生理學(xué)意義。 本研究課題以Ang II 為誘發(fā)因素,觀察其對(duì)VSMC 釋放ET-1、Ang II、ANF 和ADM 的影響及相互關(guān)系,研究了轉(zhuǎn)錄激活蛋白-1(activator protein-1,AP-1)和Janus 蛋白酪氨酸激酶-信號(hào)轉(zhuǎn)導(dǎo)及轉(zhuǎn)錄激活因子途徑( janus protein tyrosine kinase-signal transducers and activators of transcription pathway,JAK-STAT pathway)對(duì)血管活性肽基因轉(zhuǎn)錄激活的作用以及AP-1 和信號(hào)轉(zhuǎn)導(dǎo)及轉(zhuǎn)錄激活因子5(signal transducers and activators of transcription 5,STAT5)在調(diào)節(jié)基因轉(zhuǎn)錄過程中的相互關(guān)系,以期揭示Ang II 對(duì)4 種血管活性肽相對(duì)水平調(diào)節(jié)的分子機(jī)制。 1 血管舒-縮肽在血管平滑肌細(xì)胞中的表達(dá)與調(diào)控研究基因序列分析證實(shí),在Ang II、ET-1、ANF 和ADM 基因的啟動(dòng)子區(qū)中均含有AP-1的結(jié)合位點(diǎn),而且,這4種血管活性肽的表達(dá)也有賴于AP-1的活化。本部分實(shí)驗(yàn)探討了AP-1 的DNA 結(jié)合活性與4 種血管活性肽表達(dá)及其動(dòng)態(tài)平衡之間的關(guān)系以及VSMC 在該網(wǎng)絡(luò)平衡中的地位,并揭示Ang II 對(duì)4 種血管活性肽相對(duì)水平調(diào)節(jié)的分子機(jī)制。實(shí)驗(yàn)結(jié)果如下:
[Abstract]:Vasoactive peptides are small molecular peptides that regulate the vasomotor function of vascular smooth muscle cells (VSMC) and maintain vascular tension. Most of them act as autocrine and paracrine.The vasoconstrictor peptide and vasodilator peptide were divided into two groups according to their vascular effects.The former included angiotensin I(Iangiotensin IIG and endothelin-1 endothelin-1 et al. The latter included adrenomedullin adrenomedullin (ADM) and atrial natriuretic factor factor (ANFA).Under physiological conditions, the secretion and bioactivity of vasomotor active peptide were in a dynamic balance to ensure the steady state of vascular tension.There are complex positive or negative feedback regulation between different kinds of active peptides, which constitute a fine, tight vascular tension regulation network.Because most vasoconstrictive peptides have the activity of promoting hypertrophy, proliferation and migration of VSMC, the hyperactivity of vasoconstrictive peptides is often the main cause of many vascular remodeling diseases.Vasoactive peptides have the opposite effect.Therefore, the complex network formed between vasoactive peptides was studied, and the regulation mechanism of the network on vascular function was clarified.It will be helpful to understand the physiological function of vasoactive peptide system and the pathophysiological significance in the occurrence and development of cardiovascular disease.In this study, the effects of Ang II on the release of ET-1 Ang II and ADM from VSMC were observed.The effects of transcriptional activator protein-1 (AP-1) and janus protein tyrosine kinase-signal transducers and activators of transcription pathway1 (Janus) on the activation of vasoactive peptide gene, AP-1 and signal transduction were studied.The relationship between 5(signal transducers and activators of transcription 5 and STAT5 in the regulation of gene transcription.The aim of this study was to reveal the molecular mechanism of Ang II on the relative level regulation of four vasoactive peptides.1 expression and Regulation of vasomotor Peptide in Vascular smooth muscle cells; Gene sequence analysis showed that AP-1 binding sites were found in the promoter region of Ang IIET-1 and ADM genes.The expression of these four vasoactive peptides also depends on the activation of AP-1.The relationship between the DNA binding activity of AP-1 and the expression and dynamic equilibrium of four vasoactive peptides and the position of VSMC in the network equilibrium were investigated, and the molecular mechanism of the relative horizontal regulation of Ang II on the four vasoactive peptides was revealed.The results are as follows:
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2005
【分類號(hào)】：R543;Q593.3

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前1條

1 張麗君;固本化痰通脈方含藥血清對(duì)大鼠VSMC的增殖及粘附分子表達(dá)的影響[D];湖北中醫(yī)學(xué)院;2006年

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本文編號(hào)：1726836