TRPV1和TRPA1通道在心血管疾病中的作用

瞬时受体电位（TRP）通道为机体重要的非选择性阳离子通道,瞬时受体电位香草酸亚型1(TRPV1)属于TRP通道香草酸受体亚型家族成员,瞬时受体电位锚蛋白1(TRPA1)属于TRP通道超家族成员。TRPV1和TRPA1通道可调节血管内皮细胞和心肌细胞功能,其异常表达及功能改变与心血管疾病的发生发展关系密切。TRPV1通道参与心肌梗死后心脏保护和血压调节。TRPA1通道参与调节血流量、血管生成和心肌细胞凋亡。TRPV1和TRPA1通道有望成为心血管疾病的治疗靶点。     

小鼠压力过负荷心衰心肌组织中转化生子因子-β1、Ⅰ型胶原蛋白、α-平滑肌肌动蛋白及瞬时受体电位香草酸亚型4通道蛋白表达

目的同步检测转化生子因子-β1、I型胶原蛋白、α-平滑肌肌动蛋白及瞬时受体电位香草酸亚型4通道蛋白在正常和心衰小鼠心肌中的表达,观察上述因子是否参与小鼠心衰的形成。方法选用昆明系雄性小鼠,制备压力过负荷心衰模型,分为正常对照组、假手术组及过负荷心衰组,利用蛋白印迹法检测三组心肌中的转化生子因子-β1、Ⅰ型胶原蛋白、α-平滑肌肌动蛋白及瞬时受体电位香草酸亚型4通道蛋白表达。结果与正常对照及假手术组比较,压力过负荷心衰组心肌组织中转化生子因子-β1、I型胶原蛋白、α-平滑肌肌动蛋白及瞬时受体电位香草酸亚型4通道蛋白表达均明显增强(均P0.05)。结论转化生子因子-β1、I型胶原蛋白、α-平滑肌肌动蛋白及瞬时受体电位香草酸亚型4通道参与小鼠压力过负荷心衰的形成过程。     

瞬时受体电位香草酸亚型1对血压的调控和靶器官的保护作用

高血压是心血管疾病的重要危险因素之一,但目前导致高血压的具体机制尚未完全阐明。近年来越来越多的研究发现感觉神经对血压具有调控作用,而该作用需依赖表达于感觉神经的瞬时受体电位香草酸亚型1。现主要研究瞬时受体电位香草酸亚型1对血压的调控及其对靶器官的保护作用。     

TRPV1在消化系统疾病中的研究进展

瞬时受体电位香草酸亚型1(TRPV1)属于瞬时受体电位(TRP)离子通道家族,是一种非选择性阳离子配体门控通道。大量研究显示TRPV1在消化道广泛分布,且在多种消化系统疾病中发挥重要作用。近年来,TRPV1成为消化领域研究的热点。本文就TRPV1在消化系统疾病中的研究进展作一综述。     

瞬时受体电位香草酸亚型1在呼吸调节中的作用

瞬时受体电位香草酸亚型1是辣椒素的特异性受体,广泛分布于哺乳动物气道的感觉神经,被多种内外源性刺激(辣椒素、热、酸等)激活后,通过中枢及局部反射产生一系列生物学效应,如气道高反应性、神经源性炎症反应及咳嗽等.     

TRPV1通道蛋白在呼吸系统的研究进展

瞬时感受器电位离子通道蛋白(transient receptor potential ion channel protein,TRP)是细胞膜或细胞器膜上的一类非选择性Ca2+通道蛋白,通过影响细胞内Ca2+浓度来发挥众多的生理、病理功能.在TRP家族中,瞬时感受器电位香草酸受体1(transient receptor potential vanilloid 1,TRPV1)是目前分布最广、研究最多、最为关注的TRP通道蛋白,多数研究发现TRPV1在炎症的产生和痛觉的传递中发挥重要作用.本文就TRPV1在呼吸系统中的表达、功能调节和临床应用等方面作一综述.     

咳嗽反射调控机制的研究进展

咳嗽反射是机体重要的防御性反射,通过外周神经和中枢神经共同调控保持平衡,其刺激信号主要是通过迷走神经介导.咳嗽反射不仅受脑干水平影响,且大脑中枢在咳嗽反射调控过程中也发挥着重要作用.针对咳嗽反射,目前周围神经潜在的调控靶点包括瞬时受体电位香草酸受体1(TRPV1)、瞬时受体电位锚蛋白1(TRPA1)及P2X3受体,而关...     

瞬时受体电位香草酸亚型4在心血管疾病中的研究进展

瞬时受体电位香草酸亚型4(TRPV4)是一种对渗透敏感、通过容量调节的非选择性阳离子通道。研究发现其在多种系统中均发挥重要作用。近年来越来越多的研究开始探索TRPV4在心血管疾病中的作用,包括动脉粥样硬化、高血压、心肌梗死、心律失常等。然而在不同的研究中,TRPV4的作用存在一定的争议。基于此,现综述近年来关于TRPV4在心血管疾病中的研究进展,以期更深入地了解该通道在心血管系统中的作用,为后续研究提供理论基础。     

瞬时受体电位C通道与糖尿病的相关性研究进展

瞬时受体电位通道是细胞膜上一类重要的非选择性阳离子通道.1969年,Cosens和Manning[1]发现,突变体果蝇的视觉系统在持续性光刺激后可产生一种瞬时而非持续的峰电位,瞬时受体电位通道因此得名.在哺乳动物中,研究人员已发现28种瞬时受体电位通道亚型,依据氨基酸序列的同源性分属于6个亚家族[2],其中瞬时受体电位C通道是瞬时受体电位通道家族中最早发现的成员,与果蝇属的瞬时受体电位通道同源性最高.     

TRPV1在咳嗽发生机制中的作用及其药物治疗

咳嗽是呼吸系统疾病中常见的临床症状之一,与许多呼吸疾病关系密切,如哮喘、慢性阻塞性肺疾病、特发性肺纤维化、肺癌术后等[1-2]。目前,我们对引起咳嗽的机制理解仍然不足,当前的咳嗽治疗选择非常有限,治疗效果不佳,严重影响患者的生活质量。咳嗽是由于延髓咳嗽中枢受刺激,引起呼吸道感受区产生冲动传入延髓咳嗽中枢,该中枢再将冲动传向运动神经,引起呼吸肌运动产生咳嗽。瞬时受体电位香草酸亚型1(transient receptorpotentialvanilloid 1,TRPV1)是瞬时受体感受器电位通道的成员之一,广泛分布在哺乳动物的组织和器官中,是一种非选择性阳离子通道。     

瞬时受体电位香草酸亚型1通道蛋白在心肌梗死后修复和重构中的作用

目的:研究瞬时受体电位香草酸亚型1通道蛋白(TRPV1)在心肌梗死(心梗)后修复和重构中的保护作用.方法:在TRPV1基因敲除(TRPV1 -′-)小鼠和野生型(WT)小鼠左冠状动脉结扎建立心梗模型后分为TRPV1-′-心梗组、野生型心梗组;假手术组分为TRPV1-′-假手术组、野生型假手术组,监测心梗后第7天的死亡率、梗死面积.免疫组化检测成肌纤维细胞渗透和胶原成分沉积,超声心动图检测左心室重构和心功能,用酶联免疫吸附法(ELISA)测定组织转化生长因子(TGF)-β1、血管内皮生长因子和基质金属蛋白酶-2的表达水平,Western blot测定Smad2的表达.结果:心梗后第7天,TRPV1-′-心梗组的死亡率高于野生型心梗组(P＜0.05),TRPV-′-心梗组梗死面积大于野生型心梗组(P＜0.001).TRPV1-′-心梗组与野生型心梗组比较,TRPV1-′-小鼠的成肌纤维细胞渗透明显增多,胶原成分沉积增加,差异有统计学意义(P均＜0.05).TRPV1-′-心梗组比野生型心梗组左心室重构加重,心功能恶化,转化生长因子、血管内皮生长因子和基质金属蛋白酶_2的表达水平增高(P均＜0.05),磷酸化Smad2蛋白明显升高,差异均有统计学意义(P＜0.05).结论:TRPV1缺失可能通过增强TGF-β-Smad2蛋白信号通路的表达而损害心梗后修复,加重左心室重构,死亡率增加,表明TRPV1在心梗后的修复和重构中起了保护性的作用.     

瞬时受体电位香草酸亚型1受体介导疼痛的机制和治疗应用研究进展

瞬时受体电位香草酸亚型1(TRPV1)自首次成功克隆以来作为与疼痛密切相关的伤害性感受器而备受关注,其分子结构与生理功能、分布特征、激活与抑制等得到广泛研究。TRPV1受体参与炎症、脂质氧化等生物过程也与疼痛息息相关。多种内、外源性增敏剂或抑制剂可调节TRPV1通道敏感性,从而介导疼痛信号传导。TRPV1还可能通过细胞内钙超载等机制导致伤害性感受器的消融,这可能是镇痛治疗的一种潜在有效途径。该文旨在对TRPV1受体介导疼痛的相关机制及其应用研究进展作一综述。     

Transient receptor potential vanilloid subtype 1 channel mediated neuropeptide secretion and depressor effects: role of endoplasmic reticulum associated Ca2+ release receptors in rat dorsal root ganglion neurons

OBJECTIVE: This study tests the hypothesis that the transient receptor potential vanilloid subtype 1 channel induced neuropeptide secretion and depressor response are mediated by, at least in part, activation of endoplasmic reticulum associated Ca release receptors, leading to increased cytosolic Ca in dorsal root ganglion neurons. METHODS/RESULTS: Bolus injection of capsaicin (10 or 50 microg/kg), a selective transient receptor potential vanilloid subtype 1 channel agonist, into anesthetized male Wistar rats caused a dose-dependent decrease in mean arterial pressure (P < 0.05). Capsaicin (50 microg/kg)-induced depressor effects and increase in plasma calcitonin gene related peptide (CGRP) levels (-29 +/- 2 mmHg, 82.2 +/- 5.0 pg/ml) were abolished by a selective transient receptor potential vanilloid subtype 1 channel antagonist, capsazepine (3 mg/kg, -4 +/- 1 mmHg, 41.8 +/- 4.4 pg/ml, P < 0.01), and attenuated by a selective ryanodine receptor antagonist, dantrolene (5 mg/kg, -12 +/- 1 mmHg, 57.2 +/- 2.6 pg/ml, P < 0.01), but unaffected by an inhibitor of endoplasmic reticulum Ca-ATPase, thapsigargin (50 microg/kg, -30 +/- 1 mmHg, 73.8 +/- 2.3 pg/ml, P > 0.05), or an antagonist of the inositol (1,4,5)-trisphosphate receptor, 2-aminoethoxydiphenyl borate (3 mg/kg, -34 +/- 5 mmHg, 69.0 +/- 3.7 pg/ml, P > 0.05). CGRP8-37 (1 mg/kg), a selective CGRP receptor antagonist, also blocked capsaicin-induced depressor effects. In contrast, dantrolene had no effect on CGRP (1 microg/kg)-induced depressor effects. In vitro, capsaicin (0.3 micromol/l) increased intracellular Ca concentrations and CGRP release from freshly isolated sensory neurons in dorsal root ganglion (P < 0.01), which were blocked by capsazepine (10 micromol/l) and attenuated by dantrolene but not thapsigargin or 2-aminoethoxydiphenyl borate. CONCLUSION: Our results indicate that transient receptor potential vanilloid subtype 1 channel activation triggers ryanodine receptor but not inositol (1,4,5)-trisphosphate receptor dependent Ca release from endoplasmic reticulum in dorsal root ganglion neurons, leading to increased CGRP release and consequent depressor effects.     

TRP-ing up Heart and Vessels: Canonical Transient Receptor Potential Channels and Cardiovascular Disease

Transient receptor potential channels are a large superfamily of non-selective and non-voltage-gated ion channels that convey signaling information linked to a broad range of sensory inputs. In the cardiovascular system, the canonical transient receptor potential (TRPC) family has been particularly found to play a role in vascular and cardiac disease, responding to neurohormonal and mechanical load stimulation. TRPC1, TRPC3, and TRPC6 are often upregulated in models of cardiovascular disease, and their inhibition ameliorates the associated pathophysiology. Studies in gene deletion models and overexpression models of wild-type and dominant-negative proteins supports a direct role of these channels, which likely act together as heterotetramers to influence signaling. Recent evidence has further revealed the importance of protein kinase G phosphorylation as a mechanism to suppress TRPC6 channel current and dependent signaling in vascular and cardiac myocytes. This suggests a novel mechanism underlying benefits of drugs such as sildenafil, a phosphodiesterase type 5 inhibitor, nitrates, and atrial natriuretic peptides. This review describes new evidence supporting a pathophysiologic role of these three TRPC channels, and the potential utility of inhibition strategies to treat cardiovascular disease.     

血管紧张素Ⅱ受体阻滞剂与神经保护

血管紧张素Ⅱ受体阻滞剂(ARB)通过阻滞1型血管紧张素Ⅱ受体(AT1受体)降低血压、逆转血管重构,激活2型血管紧张素Ⅱ受体(AT2受体)以提高血管紧张素Ⅱ(AngⅡ)水平扩张血管、抗增殖及调脂.进一步了解ARB在神经保护中的作用机制,可为临床治疗缺血性卒中提供新的思路.     

The proximodistal aggravation of colitis depends on substance P released from TRPV1-expressing sensory neurons

Background  

Transient receptor potential vanilloid type-1 (TRPV1)-expressing sensory neurons release neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), which play a crucial role in the pathomechanism of experimental colitis. We investigated whether innervation density and neuropeptide release were responsible for the proximodistal aggravation of murine dextran-sulfate-sodium-salt (DSS) colitis.