瞬时受体电位香草酸亚型1(TRPV1)在心血管系统中的作用

TRPV1是辣椒素特异性受体，与配体结合后被激活，导致以钙离子为主的跨膜离子流动，使细胞内Ca^2＋浓度改变，进而参与痛觉整合、心血管系统调节、抗炎症反应、听力调节、胃肠功能等多种病理生理过程。     

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.     

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。     

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。     

瞬时感受器电位香草酸受体1在咳嗽发生机制中的作用及其应用前景

咳嗽是呼吸系统最常见的症状,越来越多的证据显示瞬时感受器电位香草酸受体I(TRPV1)在咳嗽发生机制中发挥重要作用.TRPV1广泛表达于人和动物的呼吸系统,能被辣椒素、酸、热和多种内源性炎性物质等激活.针对TRPV1的受体拮抗剂正在研制,有望成为新一代的镇咳药物.     

瞬时感受器电位香草酸受体1在咳嗽发生机制中的作用及其应用前景

咳嗽是呼吸系统最常见的症状,越来越多的证据显示瞬时感受器电位香草酸受体1（TRPV1）在咳嗽发生机制中发挥重要作用.TRPV1广泛表达于人和动物的呼吸系统,能被辣椒素、酸、热和多种内源性炎性物质等激活.针对TRPV1的受体拮抗剂正在研制,有望成为新一代的镇咳药物.     

瞬时受体电位通道A1亚型在冠状动脉粥样硬化性心脏病中的临床研究进展

瞬时受体电位通道A1亚型（TRPA1）是存在于细胞膜上的非选择性阳离子通道锚蛋白。TRPA1可能降低心肌再灌注损伤,TRPA1抑制剂在心血管系统中也发挥一定的作用。该文主要介绍TRPA1基本结构、功能、检测方法,TRPA1与冠状动脉粥样硬化性心脏病发病的相关性研究,TRPA1在心肌缺血再灌注损伤中的研究现状和相关治疗。     

瞬时受体电位香草酸亚型1在小鼠心肌梗死后炎症中的保护作用

目的 研究瞬时受体电位香草酸亚型1(TRPV1)在心肌梗死(MI)后炎症中的保护作用.方法 在TRPV1基因敲除(TRPV1-/-)小鼠和野生型(WT)小鼠建立MI模型,监测梗死后第3天的梗死面积、炎症细胞渗透、炎症因子和趋化因子的表达水平、心功能和第7天的生存率.结果 TRPV1-/-小鼠MI后7 d内的生存率低于野生型小鼠(62.5%比82.1%,P<0.05).MI后第3天:TRPV1-/-小鼠的梗死面积(INF)大于野生型小鼠[INF/危险区面积(AAR):69.5%±3.1%比40.1%±2.6%,P<0.05];TBPV1-/-小鼠的血浆心肌钙蛋白Ⅰ水平[(0.98±0.16)ng/ml比(0.58±0.15)ng/ml,P<0.001]、中性粒细胞[(1142±112)/mm2比(779±50)/mm2,P<0.05]和巨噬细胞渗透[(1098±58)/mm2比(664±49)/mm2,P<0.01]均高于野生型小鼠.TRPV1-/-小鼠的肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-6、巨噬细胞趋化蛋白(MCP)-1和巨噬细胞炎症蛋白(MIP)-2表达也明显高于野生型小鼠(均P<0.05).此外,与野生型小鼠比较,TRPV1-/-小鼠梗死后收缩末期和舒张末期内径进一步扩大,收缩功能恶化.结论 TRPV1基因缺失导致MI后生存率下降,炎症反应增强,心功能恶化,提示TRPV1可能通过抑制炎症和保存心功能而防止梗死扩散和心脏损伤.     

A Novel Homozygous Mutation in the Transient Receptor Potential Melastatin 6 Gene: A Case Report

Hereditary hypomagnesemia with secondary hypocalcemia (HSH) is a rare autosomal recessive disease caused by mutations in the transient receptor potential melastatin 6 (TRPM6) gene. Affected individuals present in early infancy with seizures caused by the severe hypocalcemia and hypomagnesemia. By presenting this case report, we also aimed to highlight the need for molecular genetic analysis in inbred or familial cases with hypomagnesemia. A Turkish inbred girl, now aged six years, had presented to another hospital at age two months with seizures diagnosed to be due to hypomagnesemia. She was on magnesium replacement therapy when she was admitted to our clinic with complaints of chronic diarrhea at age 3.6 years. During her follow-up in our clinic, she showed an age-appropriate physical and neurological development. In molecular genetic analysis, a novel homozygous frame-shift mutation (c.3447delT>p.F1149fs) was identified in the TRPM6 gene. This mutation leads to a truncation of the TRPM6 protein, thereby complete loss of function. We present the clinical follow-up findings of a pediatric HSH case due to a novel mutation in the TRPM6 gene and highlight the need for molecular genetic analysis in inbred or familial cases with hypomagnesemia.     

Treatment Difficulties in Hypomagnesemia Secondary to the Transient Receptor Potential Melastatin 6 Gene: A Case Report with Novel Mutation

Hypomagnesemia is a rare cause of seizures in childhood but should be kept in mind in recurrent and intractable seizures and hypocalcemia in communities where consanguineous marriages are common. Familial hypomagnesemia with secondary hypocalcemia is a rare genetic cause of hypomagnesemia, due to variants in the transient receptor potential melastatin 6 (TRPM6) genes. Here, a three year-old boy with a novel variant in this gene and had difficulties with enteral hypomagnesemia treatment is presented. He had recurrent seizures since two years of age and was diagnosed with epilepsy and treated with multiple antiepileptic drugs. Subsequently, he was diagnosed with rickets due to severe hypocalcemia at another center. The patient was hypotonic and neurodevelopmentally poor. The most prominent laboratory finding was of hypomagnesemia with secondary hypocalcemia. The genetic analysis revealed a novel variant in the TRPM6 gene. After parental treatment of intravenous magnesium (Mg²⁺) sulfate and calcium, the treatment was switched to enteral Mg²⁺ medications, due to persistent hypomagnesemia and the gastrointestinal side-effects, different oral preparations were used. The patient was stable on an oral maintenance dose of Mg²⁺ oxide with borderline blood Mg²⁺ levels and resolution of hypocalcemia. Hypomagnesemia is one of the causes of hypocalcemia. Enteral replacement is the key treatment but the treatment should be individualized for each patient. Normalization of hypomagnesemia is not always easy and should not be the aim of the treatment.     

短暂心肌缺血过程中心室晚电位的动态变化

对 38例心肌梗死恢复期的病人 ,应用数字化Holter记录仪 2 4h连续监测心室晚电位 (VLP) ,以判定心肌短暂缺血对VLP的影响。Holter中加强ST段分析软件经人为定标后 ,自动分析记录达到缺血标准的时间及程度 ,其中2 1例在Holter分析中检测出一过性心肌缺血 ,此时VLP参数总QRS波持续时间 (TQRS)、QRS波末期幅度低于 4 0uV信号持续时间 (LAS40 )明显延长 (分别为 10 7.6± 14 .3vs 98.8± 12 .7ms,36 .5± 10 .8vs2 8.4± 9.5ms;P均 <0 .0 0 1) ,QRS波末期最后 4 0ms的均方根电压 (RMS40 )幅值显著减少 (2 8.9± 17.9vs 4 3.5± 2 0 .2uV)。缺血期VLP阳性 14例 ,缺血恢复 2h后VLP阳性 7例。结论 :心肌短暂缺血发作有VLP一过性阳性改变 ,动态心电图技术可捕捉到这一变化     

Upregulation of the Vascular Alpha-1 Receptor in Malignant Doca-salt Hypertension

In this investigation we describe regulation of the vascular alpha-1 receptor and functional properties of resistance vessels in malignant hypertensive DOCA-salt rats (DOCA-salt). Uninephrectomized control and DOCA-salt rats were maintained for 6 weeks; microscopic renal morphology provided an index of vascular injury. Radioligand binding studies indicated a striking increase in the density of mesenteric alpha-1 binding sites in DOCA-salt (542 ± 44 fm/mg) vs. salt control (206 ± 4 fm/mg) and water control (223 +31 fm/mg) P < .01. The affinity of the receptor for the radioligand [¹²⁵I] (±) BE 2254 was reduced in DOCA-salt rats. Electrical nerve stimulation and agonist dose response curves were performed on isolated perfused mesenteric arteries. A singular correlation between increased receptor density and vascular responses in DOCA-salt rats could not be demonstrated. The norepinephrine (NE) content of mesenteric arteries was reduced in DOCA-salt (1001 ± 32 ng/g) vs. water control (1522 ± 44 ng/g) and saline control (1538 ± 30 ng/g) P < .01. Our results indicate, upregulation of the mesenteric alpha-1 receptor occurs in DOCA-salt rats, however, additional factors participate in the vascular response to adrenergic stimulation in this model.     

帕金森病模型大鼠海马mGluR5的表达变化及意义

目的探讨帕金森病(PD)模型大鼠海马mGluR5的表达变化及意义。方法将SD大鼠随机分为正常对照组(A组)、PD模型组(B组)和非竞争性NMDA受体拮抗剂D-AP-5+PD组(C组),通过免疫组织化学方法观察多克隆抗体mGluR5在大鼠海马的表达变化。结果正常对照组中大鼠海马有丰富的mGluR5表达;PD模型组中大鼠海马mGluR5表达明显下降;在非竞争性NMDA受体拮抗剂D-AP-5+PD组中,大鼠海马mGluR5表达又明显上调。结论帕金森病模型大鼠海马各区mGluR5表达下降,可能是神经细胞的一种自我保护作用。mGluR5可能与帕金森病认知和情感及记忆功能障碍有关。帕金森病模型大鼠海马各区经用非竞争性NMDA受体拮抗剂D-AP-5处理后,海马mGluR5表达明显上调,推测mGluR5表达下降可能在帕金森病长时程增强(LTP)诱导过程中具有重要作用,其作用机制可能为NMDA受体依赖性。