硫化氢在肺缺血/再灌注损伤中的保护作用

硫化氢(H2S)是继一氧化氮和一氧化碳之后新发现的第三种内源性气体信号分子,在机体内发挥着广泛的生物学效应。已有实验证实H2S参与肺缺血/再灌注损伤(LIRI)的病理生理过程,有抗LIRI的作用,其机制与清除氧自由基、调控炎性反应、拮抗钙超载、抑制细胞凋亡等有关,H2S的这些效应为LIRI的相关研究开辟了新的道路。     

硫化氢的中枢心血管调节机制

硫化氢(H2S)是继一氧化氮(NO)和一氧化碳(CO)之后的第3种内源性气体信号分子.研究显示H2S对神经系统、呼吸系统、消化系统和心血管系统具有调节效应,在正常生理功能和病理生理过程的调控中发挥重要生物学作用.近年来,H2S的中枢心血管调节作用逐渐引起重视,并表现出复杂的调节效果.本文主要介绍H2S对血压调节中枢相关核团的作用特点,并分析H2S在中枢心血管功能调控中的意义及其进展.     

硫化氢--心血管功能调节的新型气体信号分子

硫化氢(H2S)可以在体内由半胱氨酸在胱硫脒-β-合酶(CBS)和胱硫脒-γ-裂解酶(CSE)作用下生成,可以调节神经元兴奋性.我们系统研究并证实了内源性H2S类似一氧化氮(NO)和一氧化碳(CO),是参与心血管系统功能调节的新型气体信号分子.     

气体信号分子在心血管疾病发病中的意义

气体分子一氧化氮(NO)的发现开创了气体信号分子这一新型研究领域,目前已发现3种气体信号分子:NO、一氧化碳(CO)和硫化氢(H2S).他们在体内内源性生成,发挥广泛的生物学效应,本文仅就3种气体信号分子在心血管系统中的意义进行简要阐述.在心血管系统中内源性气体信号分子NO、CO和H2S分别与其相应的合成酶一氧化氮合酶(NOS)、血红素加氧酶(HO)和胱硫醚-γ-裂解酶(CSE)形成独立而又相互关联的体系(NO/NOS体系、CO/HO体系、H2S/CSE体系),不仅参与心血管系统生理状态下功能和结构的维持,而且在高血压、肺动脉高压、感染性休克、动脉粥样硬化等心血管疾病发病中发挥重要的病理生理学作用.     

新型气体信号分子--硫化氢心血管作用的研究进展

硫化氢(hydrogen sulfide,H2S)一直被认为是污染环境的毒性气体,是造成大气和水以及造成某些职业病的主要危害物质之一.超过生理剂量的H2S对活体器官的毒性体现在对中枢神经系统以及对呼吸系统的抑制作用[1～3].继内源性气体分子一氧化氮(nitric oxide,NO)、一氧化碳(carbonmonoxide,CO)被证实为气体信号分子后,20世纪90年代,发现半胱氨酸代谢产生的气体H2S,对神经系统特别是海马的功能具有调节作用.H2S通过刺激神经细胞,增加细胞内环腺苷酸(cyclicadenosine monophosphate,cAMP)水平,提高受体介导的兴奋性突触后电位,诱导海马的长时程增强效应[4,5].H2S可以调节消化道和血管平滑肌的张力,还可以舒张血管和抑制血管平滑肌细胞增殖[4～6].近年来研究发现,H2S还可以调节生理及病理状态下心脏的功能.本文就H2S在心血管系统中的生理学作用及其机制进行综述.     

昔日的废气,今天的气体明星——硫化氢从基础研究走向临床实践

硫化氢(H2S)一直被称为废气,20世纪90年代以来,内源性H2S的发现与研究逐渐成为生命科学和医学科学领域的研究热点[1].H2S陆续被确认为体内重要的神经递质分子、心血管调节的新型气体信号分子、肝循环调节分子、氧感受器、炎症调节因子、内皮源性血管舒张因子、外膜来源血管舒张因子、能量代谢调节因子等,在机体生理及病生理调节机制中发挥重要作用.近年来H2S基础研究的不断深入,显著推动了H2S相关的临床与药学研究进展.     

气体信号分子H2S研究进展

近年来,随着对机体内源性气体信号分子研究的深入,发现内源性H2S气体具有调节神经系统、消化系统以及心血管系统等系统功能的作用.……     

硫化氢与氧化应激

近年来的研究表明,内源性气体信号分子硫化氢(H2S)广泛参与机体多种生理、病理过程。通过查阅有关H2S与氧化应激(oxidative stress,OS)的文献并进行分析发现,H2S在许多器官和系统中起着抗氧化应激与保护组织的作用。文中就H2S在抗OS方面的研究进展作一综述。     

肺表面活性蛋白A与肺缺血-再灌注损伤

肺表面活性蛋白A(SP-A)是SP中最主要的蛋白成分,主要由Ⅱ型肺泡上皮细胞及clara细胞分泌。它具有参与局部防御、调节局部免疫和炎症等作用,并在减轻肺缺血-再灌注损伤(LIRI)方面有重要作用。现就SP-A生物学作用以及其在LIRI中的表达及研究作一综述。     

气体信号分子H2S、SO2在低氧性肺动脉高压中的作用

低氧性肺动脉高压(HPH)是一种以慢性低氧为诱因、以肺血管结构重建为基础的心血管系统疾病,具体的发病机制尚未完全阐明。研究者已发现一些小气体分子如一氧化氮(NO)、一氧化碳(CO)在调节HPH中具有重要作用。H2S、SO2是继NO和CO之后发现的新型内源性气体信号分子。本文就H2S、SO2的生成、体内分布及其在低氧性肺动脉高压中的作用进行综述。     

腺苷及其受体对肺保护的研究进展

体外循环及肺移植所引起的肺损伤的发生机制尚未完全阐明,可能与多种因素有关,其中中性粒细胞和巨噬细胞等炎性细胞的激活、肺缺血再灌注损伤为主要的影响肺功能的因素。近年来,动物实验和临床研究发现,腺苷及腺苷受体在肺保护方面有重要作用。通过刺激A2、A3腺苷受体及其信号转导通路,可以抑制中性粒细胞等炎性细胞的激活,减轻肺的缺血再灌注损伤等,文章就这些方面的最新进展做一综述。     

丹参对骨骼肌缺血再灌注损伤影响机制的研究进展

目前,对缺血再灌注损伤的研究比较多,但是大多集中在平滑肌上,对骨骼肌的研究较少。而骨骼肌缺血再灌注损伤是骨科临床常见的病理过程,大量的资料表明,缺血再灌注损伤的发生涉及能量代谢、钙、自由基、细胞黏附分子、补体等多种生物分子的含量、活性改变,在细胞凋亡方面也有很多研究,但具体机制有待进一步探讨。中药丹参具有祛瘀止血、活血调经、清心除烦的功效,对再灌注损伤相关生物分子有明显调节作用,在防治骨骼肌缺血再灌注损伤方面收到了良好的效果,并对骨骼肌缺血再灌注损伤引发的细胞凋亡有一定的干预作用,本文主要对近年来丹参在骨骼肌缺血再灌注损伤的分子机制及细胞凋亡相关因子的研究进展予以综述,以期能为骨骼肌缺血再灌注损伤的研究提供一定参考。     

Effect of endogenous hydrogen sulfide on oxidative stress in oleic acid-induced acute lung injury in rats

Background  Acute lung injury (ALI) is a common critical disease in emergency care. Oxidative stress plays an important role in the pathogenesis of ALI. Endogenous hydrogen sulfide (H₂S) can inhibit oxidative stress in rat gastric mucosal epithelium. In this study, we examined the possible role of H₂S in regulation of the oxidative stress in oleic acid-induced acute lung injury in rats.

Methods  The rat model of ALI was induced by intra-tail vein injection of oleic acid (OA). NaHS solution was injected intraperitoneally before OA injection as an OA+NaHS group. A semi-quantitative histological index of quantitative assessment of lung injury was calculated. The levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) in plasma and lung tissue were detected with ELISA. The levels of H₂S content in lung tissue were detected with an ion meter.

Results  Compared with the control group, the level of H₂S in lung tissue was significantly decreased, and the level of SOD and GSH were decreased but the level of MDA was increased in plasma and lung tissue in rats with ALI. NaHS lessened the ALI in association with an increase in the level of H₂S in lung tissue, a decrease in the level of MDA but an increase in SOD and GSH levels in plasma and lung tissues.

Conclusion  Endogenous H₂S could inhibit the oxidative stress in lung tissue in oleic acid-induced acute lung injury in rats.

     

硫化氢调节急性肺损伤大鼠肺泡上皮细胞凋亡

Background Acute lung injury (ALI) is a common syndrome associated with high morbidity and mortality in emergency. Cell apoptosis plays a key role in the pathogenesis of ALI. Hydrogen sulfide (H2S) plays a protective role during acute lung injury. We designed this study to examine the role of H2S in the lung alveolar epithelial cell apoptosis in rats with acute lung injury. Methods Sixty-nine male Sprague Dawley rats were used. ALI was induced by intra-tail vein injection of oleic acid (OA). NaHS solution was injected intraperitonally 30 min before OA injection as NaHS pretreatment group. Single sodium hydrosulfide pretreatment group and control group were designed. Index of quantitative assessment (IQA) and the percentage of polymorphonuclear leucocyte (PMN) cells in the bronchoalveolar lavage fluid (BALF) were calculated. H2S level in lung tissue was measured by sensitive sulphur electrode. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Fas protein was measured by immunohistochemical staining. Results The level of endogenous H2S in lung tissue decreased in the development of ALI induced by OA injection. Apoptosis and Fas protein in alveolar epithelial cells increased in ALI of rats but NaHS lessened apoptosis and Fas protein expression in alveolar epithelial cells of rats with ALI. Conclusion Endogenous H2S protects rats from oleic acid-induced acute lung injury probably by inhibiting cell apoptosis.     

缺血再灌注损伤与Ryanodine受体研究进展

缺血再灌注损伤在临床中十分常见而且难以避免,可导致较高的病残率。从其发病机制的不同环节进行治疗是减轻缺血再灌注损伤较为理想的方法。细胞内游离钙被认为在缺血再灌注后导致细胞死亡的级联反应中发挥主要作用。近年来对细胞内钙通道Ryanodine受体阻滞剂丹曲林的研究进展迅速,其药理作用机制主要是抑制细胞内质网和肌浆网的钙释放。本文对缺血再灌注损伤及Ryanodine受体等细胞内钙通道予以综述。     

福辛普利对心肌缺血再灌注损伤心肌细胞的作用和对Bcl-2、Bax表达的影响

目的探讨福辛普利对大鼠心肌缺血再灌注模型心肌细胞凋亡及相关调控基因Bcl-2、Bax表达的影响及相关机制。方法24只动物随机分成假手术组（n=8），缺血再灌注损伤组（n=8）和福辛普利预处理组（n=8），再灌注24h后处死动物。用透射电镜观察大鼠心肌超微结构的变化，TUNEL法检测心肌细胞凋亡，RT-PCR检测Bcl-2及Bax基因表达。结果电镜结果显示福辛普利的应用促使缺血再灌注大鼠心肌组织肌原纤维排列趋于恢复正常、线粒体肿大好转、细胞核和核仁显示良好，无细胞核变形，无胞核空洞样变及核固缩等现象。TUNEL显示福辛普利组细胞凋亡明显减少。缺血再灌注损伤24h后心肌组织Bcl-2基因表达较假手术组显著降低，而Bax基因表达则显著增高，福辛普利则可以逆转这种趋势。结论应用福辛普利能抑制心肌缺血再灌注损伤导致的心肌细胞凋亡，发挥心肌保护作用，从而缓解缺血再灌注损伤的发生发展。     

H2S Protecting against Lung Injury following Limb Ischemia-reperfusion by Alleviating Inflammation and Water Transport Abnormality in Rats

Objective To investigate the effect of H2 S on lower limb ischemia-reperfusion(LIR) induced lung injury and explore the underlying mechanism. Methods Wistar rats were randomly divided into control group, IR group, IR+ Sodium Hydrosulphide(NaHS) group and IR+ DL-propargylglycine(PPG) group. IR group as lung injury model induced by LIR were given 4 h reperfusion following 4 h ischemia of bilateral hindlimbs with rubber bands. NaHS(0.78 mg/kg) as exogenous H2 S donor and PPG(60 mg/kg) which can suppress endogenous H2 S production were administrated before LIR, respectively. The lungs were removed for histologic analysis, the determination of wet-to-dry weight ratios and the measurement of mRNA and protein levels of aquaporin-1(AQP1), aquaporin-5(AQP5) as indexes of water transport abnormality, and mRNA and protein levels of Toll-like receptor 4(TLR4), myeloid differentiation primary-response gene 88(MyD88) and p-NF-κB as indexes of inflammation. Results LIR induced lung injury was accompanied with upregulation of TLR4-Myd88-NF-κB pathway and downregulation of AQP1/AQP5. NaHS pre-treatment reduced lung injury with increasing AQP1/AQP5 expression and inhibition of TLR4-Myd88-NF-κB pathway, but PPG adjusted AQP1/AQP5 and TLR4 pathway to the opposite side and exacerbated lung injury. Conclusion Endogenous H2 S, TLR4-Myd88-NF-κB pathway and AQP1/AQP5 were involved in LIR induced lung injury. Increased H2 S would alleviate lung injury and the effect is at least partially depend on the adjustment of TLR4-Myd88-NF-κB pathway and AQP1/AQP5 expression to reduce inflammatory reaction and lessen pulmonary edema.     

Hydrogen sulfide donor regulates alveolar epithelial cell apoptosis in rats with acute lung injury

Background Acute lung injury (ALl) is a common syndrome associated with high morbidity and mortality in emergency medicine.Cell apoptosis plays a key role in the pathogenesis of ALl.Hydrogen sulfide (H...     

Expression of integrin alpha v beta 6 in rats with ventilator-induced lung injury and the attenuating effect of synthesized peptide S247.

BACKGROUND: High tidal volume ventilation can cause inflammatory reaction in lungs. Integrins are associated with regulating lung inflammation and edema following acute lung injury. Integrin alpha v beta 6 expression in ventilator-induced lung injury (VILI) and the ability of the RGD-peptidomimetic agent S247 to attenuate VILI in rats were investigated. MATERIAL/METHODS: Eighteen adult male rats were assigned to three groups: controls (C: n=6) with no ventilation; high tidal volume lung ventilation (H: n=6); and such ventilation after treatment with S247 (HS: n=6). HS was injected with 50 mg/kg S247 18 h before and then i.p injection every 3 h until the start of ventilation. The others received saline. Assessed were lung histopathology, wet-to-dry weight ratios, total protein content, white blood cell (WBC) counts, macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-alpha (TNF-alpha) concentrations in the bronchoalveolar lavage fluid (BALF) and integrin alpha v beta 6 mRNA and protein expression. RESULTS: Wet-to-dry weight ratios and BALF WBCs and total protein content were different among the groups (p<0.01). Lung injury score and integrin alpha v beta 6 mRNA level were lower in HS than in H (p<0.01). Integrin alpha v beta 6-positive staining was mainly on alveolar walls and the immunoreactivity of HS was clearly less than in H. TNF-alpha was not detected in C and was significantly lower in HS than in H (p<0.05). MIP-2 concentration in H was higher than in C and HS (p<0.01). CONCLUSIONS: Pretreatment with S247 attenuated VILI, suggesting pulmonary epithelial integrins are involved in its pathogenesis and agents such as S247 may be useful in treating it.     

脑缺血再灌注损伤大鼠全血内源性一氧化碳含量及海马组织中血红素加氧酶1活性的变化

目的观察大鼠脑缺血再灌注损伤后内源性一氧化碳含量及海马血红素加氧酶1(HO-1)的变化。方法 80只雄性SD大鼠随机分为假手术组和模型组。模型组通过栓塞大鼠大脑中动脉并于1h后再灌注制备局灶性缺血再灌注损伤模型,假手术组仅施行颈部切开及游离右颈总动脉,不结扎,亦不予栓塞。以生物化学法检测2组大鼠全血碳氧血红蛋白(COHb)的含量以及海马组织中HO-1的活性。结果脑缺血再灌注损伤后,模型组全血COHb含量和海马组织中HO-1的活性在各时间点均高于假手术组(P<0.05),并均在再灌注24h达到高峰。结论大鼠脑缺血再灌注损伤后可引起全血COHb含量的升高和海马中HO-1的活性升高。