中枢神经系统H2S的作用及机制研究进展

中枢神经系统内源性硫化氢 (H2 S)主要由胱硫醚 β 合酶合成。脑内H2 S对中枢神经系统多种生理和病理过程有重要的影响 :(1)H2 S通过cAMP途径 ,易化海马长时程增强的产生 ;(2 )H2 S通过下丘脑 垂体 肾上腺轴来参与神经内分泌功能的调节 ;(3)H2 S协同一氧化氮松弛脑血管平滑肌 ,从而调节血压。此外 ,H2 S还与脑血管损害、多种遗传性疾病的脑功能障碍有关     

内源性硫化氢对慢性应激结肠高动力的影响

本文旨在探讨内源性硫化氢(hydrogen sulfide,H2S)与慢性应激大鼠结肠高动力的关系。大鼠随机分为慢性避水应激(water avoidance stress,WAS)组和假避水应激(sham water avoidance stress,SWAS)组,记录大鼠每日1 h应激期间大便粒数,连续10 d;分别制作结肠平滑肌条,使用生物机能实验系统记录两组肌条自发性收缩活性以及SWAS组H2S合成酶抑制剂预处理后收缩活性;测定结肠内源性H2S的产生浓度;采用免疫组化和Western blot等方法观察结肠内源性H2S合成酶分布及表达。结果显示,WAS组大鼠应激期间大便粒数、结肠肌条收缩的曲线下面积(area under the curve,AUC)均高于SWAS组(P0.05);WAS组结肠内源性H2S产生量明显低于SWAS组(P0.001);H2S合成酶胱硫醚-γ-裂解酶(cystathionine-γ-lyase,CSE)在纵行肌条和环形肌条细胞浆、肌间神经元细胞核中强表达,胱硫醚-β-合成酶(cystathionine-β-synthase,CBS)主要表达于肌间神经元胞浆;与SWAS组相比,WAS组大鼠结肠(去除粘膜及粘膜下层后)CBS和CSE的表达下调(P0.001);H2S合成酶抑制剂明显增加SWAS组肌条收缩的AUC(P0.001)。以上结果表明,内源性H2S合成酶表达下调、H2S合成减少是慢性应激结肠高动力的原因之一。     

硫化氢在低氧性肺动脉高压发病中的作用

低氧性肺动脉高压(HPH)是临床众多心肺血管疾病发生、发展中重要的病理过程,也是决定这些疾病的进展及预后的重要因素之一.HPH又是复杂的病理生理过程,其发病机制迄今尚未完全阐明.近来发现,一直被称为有毒废气的硫化氢(H2S)可在机体内源性生成,外源性给予H2S可以缓解HPH和肺血管结构重建,其作用机制包括舒张血管、调节血管平滑肌细胞增殖/凋亡失衡、抑制肺动脉细胞外基质异常堆积等,进而揭示了H2S在HPH中的重要调节作用.     

硫化氢在不同诱因致急性肺损伤中的作用

硫化氢（Hydrogensulfide,H2S）是一种具有臭鸡蛋气味的有毒气体,其毒理作用的主要靶器是中枢神经系统和呼吸系统,亦可伴有心脏等多器官损害。上世纪90年代中期,人们发现体内含硫氨基酸代谢生成的内源性H2S对神经系统特别是海马的功能具有调节作用,并可调节消化道和血管平滑肌的张力,从而对H2S有了新认识。如今,     

硫化氢对家兔窦房结起搏细胞的电生理效应

本研究应用细胞内微电极技术,观察硫化氢(hydrogen sulfide,H2S)对家兔窦房结起搏细胞的电生理效应.结果表明:(1)NaHs(H2S供体)50、100、200 μmol/L浓度依赖地降低家兔窦房结起搏细胞4相去极化速率及起搏放电频率.(2)ATP敏感性钾(ATP-sensitive K ,KATP)通道阻断剂格列苯脲(glybenclamide,Gli,20 μmol/L)阻断NariS(100 μmol/L)的电生理效应.(3)预先应用起搏离子流(pacemaker currenL,If)通道阻断剂氯化铯(CsCl,2 mmol/L)对Naris(100μmol/L.)的电生理效应无影响.(4)胱硫醚-γ裂解酶(cystathionine γ-lyase,CSE)的不可逆抑制剂DL-propargylglycine (PPG,200 μmol/L)的家兔窦房结起搏细胞的动作电位参数无影响.以上结果提示,H2S对家兔窦房结起搏细胞有负性变时作用,这些效应可能与其开放KATP通道,增加K 外流有关,与If无关.本实验没有发现窦房结起搏细胞内有CSE催化产生的内源性H2S的合成.     

硫化氢对抗脑缺血再灌注损伤的机制研究进展

硫化氢（H2S）是一种新型内源性气体信使分子,在许多生理和病理生理过程中,尤其在神经保护中,扮演重要角色,既是神经调节剂, 也是神经保护剂。近年来的研究发现,H2S对于脑缺血再灌注损伤具有积极的防治作用,它可通过抗氧化应激、抗炎及抗细胞凋亡等多个途径, 对脑缺血再灌注损伤起保护作用,具有良好的临床应用前景。简介脑内H2S生成途径,综述H2S在中枢神经系统中的生物学效应及其对脑 缺血再灌注损伤的保护作用与机制研究进展,以期为脑缺血再灌注损伤的临床防治提供新思路。     

硫化氢对炎症和急危重症作用机制的研究进展

一直以来硫化氢（Hydrogensulfide,H2S）被认为是具有臭鸡蛋气味的有毒气体。关于H2S的研究主要集中在毒性方面,人接触H2S可导致如眼炎、化学性肺炎、肺水肿、上消化道不适,中枢神经系统等症状,甚至猝倒呈闪电样死亡[1]。20世纪90年代末,人们发现内源性H2S的存在。研究证实,H2S作为一种新型内源性气体信号分子,参与心血管、神经、呼吸、消化、内分泌及免疫系统等多个系统的病理生理过程。     

硫化氢在肺血管重塑中的调节机制及信号通路

以肺动脉压力进行增高为特征的肺动脉高压(PH)是临床上棘手的疾病之一,而肺血管重塑是导致肺动脉高压的关键环节。内源性硫化氢(H2S)是继一氧化氮和一氧化碳之后发现的第三种气体信号分子,具有多种生物效应,其作用也愈加受到关注。大量研究表明H2S可以调节肺血管重塑,与PH的发生及转归具有密切关系。本文主要集中阐述近年来H2S及其在PH的血管重塑中调节机制以及信号通路的新进展,旨在为PH的防治提供新的思路和启发。     

“废气不废”:气体信号分子硫化氢的研究进展

内源性气体信号分子的发现开辟了"废气不废"的新思路。硫化氢(hydrogen sulfide,H2S)是继一氧化氮(nitric oxide,NO)和一氧化碳(carbon monoxide,CO)之后的气体信号分子家系新成员。近年来,人们对H2S的内源性生成、生物学效应及其机制,特别是其在心血管、神经、呼吸、内分泌等系统的疾病发生、发展过程中的病理生理学意义进行了广泛研究。本文综述了近年来H2S相关基础、临床以及药学研究方面的进展,包括H2S对细胞增殖和凋亡、炎症反应、血管新生及离子通道的调节作用,H2S在各种系统疾病发病中的调节作用,H2S供体及其在药学领域的研究进展。     

含硫气体信号分子对心血管调节的效应及机制研究进展

含硫气体信号分子硫化氢(hydrogen sulfide,H2S)和二氧化硫(sulfur dioxide,SO2)过去被认为是废气,但是研究先后发现这两种含硫气体能在哺乳动物体内通过含硫氨基酸代谢内源性生成。心血管系统存在H2S和SO2的生成体系,并且H2S和SO2具有重要的心血管生理学效应,包括舒张血管和心肌负性肌力作用。H2S和SO2的心血管病理生理学效应也逐渐被认识,如缓解高血压和肺动脉高压、抑制动脉粥样硬化进展、保护心肌缺血再灌注损伤和异丙肾诱导的心肌损伤。ATP敏感性钾通道、L型钙通道、c GMP、NF-κB信号通路及MAPK信号通路等都参与H2S和SO2的生物学效应。以上发现表明H2S和SO2是重要的心血管内源性气体信号分子,为阐明心血管疾病的发病机制和治疗靶点提供新的思路。     

硫化氢神经生物学作用的研究进展

硫化氢(hydrogen sulfide,H_2S)作为继一氧化碳、一氧化氮后的第三种新型气体信号分子,得到了研究者们的广泛关注。H_2S在生物机体内发挥了重要的神经生物学作用。本综述主要总结H_2S的神经保护作用和神经调质功能及其机制,并介绍近几年人们对H_2S在神经系统疾病中的作用的研究进展。     

Hydrogen sulfide regulates cAMP homeostasis and renin degranulation in As4.1 and rat renin-rich kidney cells

The present study aims to investigate the regulatory effect of hydrogen sulfide (H(2)S) on cAMP homeostasis and renin degranulation in As4.1 and rat renin-rich kidney cells. It was found in the present study that NaHS at 0.1-10 μM significantly decreased cAMP production in As4.1 cells treated with isoproterenol (a β-adrenoceptor agonist), forskolin (an adenylyl cyclase activator), or 3-isobutyl-1-methylxanthine (IBMX, a phosphodiesterase inhibitor). NaHS at 10 μM suppressed adenylate cyclase activity but stimulated phosphodiesterase activity. We continued to study whether H(2)S may mediate cAMP-dependent renin degranulaion in As4.1 cells. It was found that NaHS at 0.1-10 μM significantly increased intracellular renin protein level. Moreover, NaHS reversed the declined renin content within As4.1 cells and normalized the upregulated renin activity in the culture medium of As4.1 cells treated with the above three stimuli. RT-PCR showed that cystathionine-γ-lyase is the main enzyme to produce endogenous H(2)S in As4.1 cells. Overexpression of cystathionine-γ-lyase increased endogenous H(2)S production and suppressed isoproterenol-induced renin release, suggesting that endogenous H(2)S may also inhibit renin release from As4.1 cells. We also tested whether H(2)S has a similar effect in renin-rich kidney cells. It was found that isoproterenol elevated intracellular cAMP level and extracellular renin activity but decreased renin protein level in the renin-rich kidney cells. Pretreatment with NaHS abolished these effects. In conclusion, H(2)S regulates cAMP homeostasis via inhibition of adenylate cyclase and stimulation of phosphodiesterase. Our findings suggest that H(2)S plays a critical role in regulation of renin degranulation in As4.1 and rat renin-rich kidney cells.     

Inducible hydrogen sulfide synthesis in chondrocytes and mesenchymal progenitor cells: is H2S a novel cytoprotective mediator in the inflamed joint?

Hydrogen sulfide (H(2)S) has recently been proposed as an endogenous mediator of inflammation and is present in human synovial fluid. This study determined whether primary human articular chondrocytes (HACs) and mesenchymal progenitor cells (MPCs) could synthesize H(2)S in response to pro-inflammatory cytokines relevant to human arthropathies, and to determine the cellular responses to endogenous and pharmacological H(2)S. HACs and MPCs were exposed to IL-1β, IL-6, TNF-α and lipopolysaccharide (LPS). The expression and enzymatic activity of the H(2)S synthesizing enzymes cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) were determined by Western blot and zinc-trap spectrophotometry, respectively. Cellular oxidative stress was induced by H(2)O(2), the peroxynitrite donor SIN-1 and 4-hydroxynonenal (4-HNE). Cell death was assessed by 3-(4,5-dimethyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Mitochondrial membrane potential (DCm) was determined in situ by flow cytometry. Endogenous H(2) S synthesis was inhibited by siRNA-mediated knockdown of CSE and CBS and pharmacological inhibitors D,L-propargylglycine and aminoxyacetate, respectively. Exogenous H(2)S was generated using GYY4137. Under basal conditions HACs and MPCs expressed CBS and CSE and synthesized H(2)S in a CBS-dependent manner, whereas CSE expression and activity was induced by treatment of cells with IL-1β, TNF-α, IL-6 or LPS. Oxidative stress-induced cell death was significantly inhibited by GYY4137 treatment but increased by pharmacological inhibition of H(2)S synthesis or by CBS/CSE-siRNA treatment. These data suggest CSE is an inducible source of H(2)S in cultured HACs and MPCs. H(2)S may represent a novel endogenous mechanism of cytoprotection in the inflamed joint, suggesting a potential opportunity for therapeutic intervention.     

气体信号分子硫化氢在植物中的生理功能及作用机制

硫化氢（hydrogen sulfide,H2S）是继一氧化氮（nitric oxide,NO）和一氧化碳（carbon monoxide,CO）之后发现的第3种气体信号分子,它能参与生物体内的多种生理生化过程并发挥特定功能。在动物体内,H2S能够调节血管及神经系统功能。植物也能通过产生内源H2S来提高对环境的适应能力,缓解多种逆境胁迫造成的损伤和毒害,参与特定的生理代谢过程,诸如参与气孔运动和延缓衰老等。本文从H2S产生和代谢途径、已发现的生理功能和信号转导机制等方面综述H2S在植物中的最新研究进展,同时也探讨了H2S与其它信号分子的相互作用以及H2S对蛋白质的修饰机制。     

Estimation of hydrogen sulphide in the human lymphocytes

Hydrogen sulphide (H2S), a signaling gasotransmitter and a potent vasorelaxant is endogenously produced by the enzymes cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE). CBS is a predominant source of H2S in the central nervous system, while CSE is the major H2S producing enzyme in the brain and other nervous tissues. Though the expression of these enzymes in the blood lymphocytes is known, H2S formation in the lymphocytes has not been reported so far. In the present study, H2S levels in the lymphocytes of healthy control subjects were estimated, after suitable modifications in a routine method [Stipanuk M H & Beck P W (1982) Biochem J 206, 267-277] used for detecting tissue levels of H2S. In this method, homocysteine (Hcys) due to its higher solubility was used as the substrate in place of L-cysteine and NaOH was used in place of zinc acetate to increase the entrapment of H2S in the central well. A mean H2S level of 11.64 +/- 6.36 microM/min/mg protein was detected in the lymphocytes of 8 subjects (mean age, 24 +/- 2; 2 male, 6 female). The modified method was found to be more sensitive for H2S estimation in human lymphocytes. As endogenous H2S is reported to be involved in the pathogenesis of various cardiovascular and pulmonary diseases, the levels of H2S in lymphocytes can be a marker of the endogenous tissue levels.     

Gaso-transmitter hydrogen sulphide: potential new target in pharmacotherapy

Research in the last two decades has transformed the way hydrogen sulphide (H2S) is perceived from a noxious gas to a gaso-transmitter with a vast potential in pharmacotherapy. H2S is synthesized in various body-systems using the enzymes cystathionine beta-synthase and cystathionine gamma-lyase; either of these being the predominat enzyme in a particular system. H2S may be one of the physiological modulators of blood pressure in humans. The gas relaxes the vascular smooth muscle cells by opening up K(ATP) channels. Moreover, it suppresses the proliferation of vascular smooth muscle cells. H2S may also be contributing in the protection afforded by ischaemia-preconditioning. Testosterone is thought to be responsible for the higher central nervous system level of H2S in males. In the central nervous system, H2S is implicated in Alzheimer's disease, epilepsy, stroke and Down's syndrome. Insulin secretion is associated with a decrease in the H2S levels. Raised H2S is detrimental in acute pancreatitis as well as in septic shock. Recently, H2S-releasing derivatives of certain drugs have shown promise in protection against gastric ulcer and in inflammatory bowel disease. The beneficial effects of certain sulphur containing herbs like ginseng and garlic may be mediated via H2S. In future, development of specific drugs modulating H2S levels may prove beneficial in varied disorders.     

Hydrogen sulfide as a vasodilator

Gases such as nitric oxide (NO) and carbon monoxide (CO) play important roles both in normal physiology and in disease. The toxic effects of hydrogen sulphide (H2S) on living organisms have been recognized for nearly 300 years. In recent years, however, interest has been directed towards H2S as the third gaseous mediator, which has been shown to exhibit potent vasodilator activity both in vitro and in vivo most probably by opening vascular smooth muscle K(ATP) channels. Of the two enzymes, cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthetase (CBS), which utilize L-cysteine as substrate to form H2S, CSE is believed to be the key enzyme which forms H2S in the cardiovascular system. Recent studies have shown an important role of the vasodilator action of H2S in health and disease.     

The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener.

Hydrogen sulfide (H(2)S) has been traditionally viewed as a toxic gas. It is also, however, endogenously generated from cysteine metabolism. We attempted to assess the physiological role of H(2)S in the regulation of vascular contractility, the modulation of H(2)S production in vascular tissues, and the underlying mechanisms. Intravenous bolus injection of H(2)S transiently decreased blood pressure of rats by 12- 30 mmHg, which was antagonized by prior blockade of K(ATP) channels. H(2)S relaxed rat aortic tissues in vitro in a K(ATP) channel-dependent manner. In isolated vascular smooth muscle cells (SMCs), H(2)S directly increased K(ATP) channel currents and hyperpolarized membrane. The expression of H(2)S-generating enzyme was identified in vascular SMCs, but not in endothelium. The endogenous production of H(2)S from different vascular tissues was also directly measured with the abundant level in the order of tail artery, aorta and mesenteric artery. Most importantly, H(2)S production from vascular tissues was enhanced by nitric oxide. Our results demonstrate that H(2)S is an important endogenous vasoactive factor and the first identified gaseous opener of K(ATP) channels in vascular SMCs.