一氧化碳在心血管系统中的调控作用

一氧化碳作为众所周知的毒性气体,其毒性机制早已阐明。然而,在机体内一氧化碳可以被内源合成,并在心血管系统中发挥了重要生理调节功能。这些生理调节功能机制的初步阐明提示我们一氧化碳可能可以作为多种心血管疾病的治疗靶点,这值得未来更多开创性的研究。     

Carbon Monoxide Promotes Lateral Root Formation in Rapeseed

Carbon monoxide (CO), an odorless, tasteless and colorless gas, has recently proved to be an important bioactive or signalmolecule in mammalian cells, with its effects mediated mainly by nitric oxide (NO). In the present report, we show thatexogenous CO induces lateral root (LR) formation, an NO-dependent process. Administration of the CO donor hematin torapeseed (Brassica napus L. Yangyou 6) seedlings for 3 days, dose-dependently promoted the total length and number ofLRs. These responses were also seen following the application of gaseous CO aqueous solutions of different saturatedconcentrations. Furthermore, the actions of CO on seedlings were fully reversed when the CO scavenger hemoglobin (Hb)or the CO-specific synthetic inhibitor zinc protoporphyrin-IX (ZnPPIX) were added. Interestingly, depletion of endogenousNO using its specific scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (cPTIO)or the nitric oxide synthase (NOS) inhibitor N~G-nitro-L-arginine methyl ester (L-NAME),led to the complete abolition ofLR development, illustrating an important role for endogenous NO in the action of CO on LR formation. However, theinduction of LR development by 200 umol/L sodium nitroprusside (SNP),an NO donor, was not affected by the presenceor absence of ZnPPIX. Furthermore, using an anatomical approach combined with laser scanning confocal microscopywith the NO-specific fluorophore 4,5-diaminofluorescein diacetate, we observed that both hematin and SNP increased NOrelease compared with control samples and that the NO signal was mainly distributed in the LR primordia (LRP), especiallyafter 36 h treatment. The LRP were found to have similar morphology in control, SNP-and hematin-treated seedlings.Similarly, the enhancement of the NO signal by CO at 36 h was differentially quenched by the addition of cPTIO, L-NAME,ZnPPIX and Hb. In contrast, the induction of NO caused by SNP was not affected by the application of ZnPPIX. Therefore,we further deduced that CO induces LR formation probably mediated by the NO/NOS pathway and NO may act downstreamof CO signaling, which has also been shown to occur in animals.     

急性一氧化碳中毒131例临床分析

目的：探讨急性一氧化碳中毒（ACOP）患者的发病特点、临床表现及其对预后的影响。方法：回顾性分析2006年1月一2011年12月我院收治的131例ACOP患者,将其按病情的严重程度分为轻、中、重度3组,比较各组的发病原因和临床表现。结果：接触时间、基础疾病、血清肌酸激酶（CK）、昏迷时间在3组间差异有显著性（P〈0．01）,年龄、性别、中毒原因方面3组间差异无显著性（P〉0．05）。迟发性脑病组和无迟发性脑病组在年龄、基础疾病、并发症、接触时间、昏迷时间、CK方面差异有显著性（P〈0．01）;而在性别、中毒原因方面差异无显著性（P〉0．05）。结论：对于ACOP患者而言,接触时间长、伴有基础疾病、昏迷时间长、CK高不仅提示病情的严重程度,更是迟发性脑病的易患因素。而高压氧治疗是ACOP的首选及有效的治疗方法。     

Carbon Monoxide Promotes Lateral Root Formation in Rapeseed

Carbon monoxide (CO), an odorless, tasteless and colorless gas, has recently proved to be an important bioactive or signal molecule in mammalian cells, with its effects mediated mainly by nitric oxide (NO). In the present report, we show that exogenous CO induces lateral root (LR) formation, an NO-dependent process. Administration of the CO donor hematin to rapeseed (Brassica napus L. Yangyou 6) seedlings for 3 days, dose-dependently promoted the total length and number of LRs. These responses were also seen following the application of gaseous CO aqueous solutions of different saturated concentrations. Furthermore, the actions of CO on seedlings were fully reversed when the CO scavenger hemoglobin (Hb)or the CO-specific synthetic inhibitor zinc protoporphyrin-Ⅸ (ZnPPIX) were added. Interestingly, depletion of endogenous NO using its specific scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (cPTIO)or the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME), led to the complete abolition of LR development, illustrating an important role for endogenous NO in the action of CO on LR formation. However, the or absence of ZnPPIX. Furthermore, using an anatomical approach combined with laser scanning confocal microscopy with the NO-specific fluorophore 4,5-diaminofluorescein diacetate, we observed that both hematin and SNP increased NO release compared with control samples and that the NO signal was mainly distributed in the LR primordia (LRP), especially after 36 h treatment. The LRP were found to have similar morphology in control, SNP- and hematin-treated seedlings.Similarly, the enhancement of the NO signal by CO at 36 h was differentially quenched by the addition of cPTIO, L-NAME,ZnPPIX and Hb. In contrast, the induction of NO caused by SNP was not affected by the application of ZnPPIX. Therefore,we further deduced that CO induces LR formation probably mediated by the NO/NOS pathway and NO may act downstream of CO signaling, which has also been shown to occur in animals.     

急性一氧化碳中毒大鼠海马组织NaPi-IIb 蛋白表达的研究

目的:研究急性一氧化碳中毒后大鼠海马组织NaPi-IIb蛋白的表达情况。方法:选取雄性Sprague-Dawley(SD)大鼠48只,随机分为正常对照组(NC组)14只、缺氧组(IB组)17只、急性CO中毒组(CO-P组)17只。利用简易密闭容器建立缺氧模型;利用多次追加腹腔注射CO气体染毒的方法建立急性一氧化碳中毒模型。观察各组大鼠在建模过程中呼吸、活动改变情况。大鼠于建模24 h-26 h后取脑组织制作石蜡切片,选取海马组织平面利用免疫组织化学染色(IHC)观察组织形态及海马组织中NaPi-IIb蛋白的表达情况。同时,分离各组大鼠海马组织,利用蛋白质免疫印迹技术(Western Blot,WB)检测海马组织中NaPi-IIb蛋白的表达情况。结果:IHC、WB结果表明海马组织中NaPi-IIb蛋白的表达在CO-P组中明显高于NC组、IB组(P0.05)。NC组、IB组比较,NaPi-IIb蛋白的表达无明显差异(P0.05)。结论:在本研究中,CO暴露后,大鼠海马组织NaPi-IIb蛋白表达的增高与CO相关。NaPi-IIb蛋白可能成为CO中毒稳定、可靠的诊断标志物。     

外源一氧化碳对干旱胁迫下水稻幼苗抗氧化系统的影响

以水稻(Oryza sativa L.) 品种‘D奇宝优1号'幼苗为材料,采用20%聚乙二醇(PEG-6000)模拟水分胁迫,研究外源一氧化碳(CO)对干旱胁迫下水稻幼苗抗氧化能力的影响,以探索CO提高水稻幼苗抗旱性的机制.结果显示,CO供体高铁血红素(Hematin,H)显著降低干旱胁迫下水稻幼苗叶片质膜相对透性和丙二醛(MDA)含量,提高脯氨酸和可溶性蛋白的含量,不同程度地促进叶片中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和过氧化物酶(POD)的活性,而CO清除剂血红蛋白(Hemoglobin,Hb)则逆转CO供体对干旱胁迫下水稻幼苗氧化损伤的缓解效应.由此表明,外源CO能通过调整保护酶活性和渗透调节物质含量来提高水稻幼苗的抗氧化能力,有效增强其抗旱性.     

外源一氧化碳对小麦幼苗耐盐性以及根中脯氨酸含量的影响

小麦幼苗经饱和度为50％的一氧化碳（C0）溶液预处理24h可以缓解随后以200mmol·L^-1NaCl处理所导致的小麦幼苗生长的受抑程度和相对含水量的下降。CO预处理还可有效提高盐胁迫下小麦幼苗根中吡咯啉-5-羧酸合成酶（P5CS）活性及其基因的表达,同时抑制脯氨酸脱氢酶（ProDH）活性,从而诱导脯氨酸的大量合成,缓解盐胁迫对小麦幼苗的伤害。     

Carbon Monoxide Alleviates Salt-Induced Oxidative Damage in Wheat Seedling Leaves

Carbon monoxide （CO）, a by-product released during the degradation of heme by heme oxygenases （EC 1.14.99.3） In animals, is regarded as an important physiological messenger or bioactive molecule involved in many biological events that has been recently reported as playing a major role in mediating the cytoprotectlon against oxidant-induced lung Injury. In the present study, we first determined the protective effect of exogenous CO against salt-induced oxidative damage in wheat seedling leaves. Wheat seedlings treated with 0.01μmol/L hematin as the CO donor demonstrated significant reversal of chlorophyll decay, dry weight, and water loss induced by 300 mmol/L NaCl stress. Interestingly, the increase in lipid peroxidation observed in salt-treated leaves was reversed by 0.01μmol/L hematin treatment. Time-couree analyses showed that application of 0.01μmol/L hematln enhanced gualacol peroxidase, superoxide dismutase, ascorbate peroxidase and catalase activities in wheat seedling leaves subjected to salt stress. These effects are specific for CO because the CO scavenger hemoglobin （1.2 mg/L） blocked the actions of the CO donor hematln. However, higher concentration of the CO donor （1.0μmol/L） did not alleviate dry weight and water loss of salt-stressed wheat seedlings. These results suggest that exogenous application of low levels of a CO donor may be advantageous against salinity toxicity.     

Hydrogen Sulfide and Carbon Monoxide Are in Synergy with Each Other in the Pathogenesis of Recurrent Febrile Seizures

1. The purpose of the present study was to investigate the interaction between hydrogen sulfide (H(2)S) and carbon monoxide (CO) during recurrent febrile seizures (FS) 2.H(2)S and CO are important intra- and intercellular messengers, regulating various brain functions. Our recent studies showed that both of them alleviate the hippocampal damage induced by recurrent FS. In the present study, on a rat model of recurrent FS, we found that hydroxylamine (an inhibitor of cystathionine b-synthase, CBS) reduced CO level and down regulated heme oxygenase (HO-1) expression, while NaHS (a donor of H(2)S) elevated CO level and upregulated HO-1 expression. ZnPP-IX (an inhibitor of HO-1) decreased H(2)S formation and down regulated CBS expression, while hemin (which increases the production of endogenous CO) enhanced H(2)S formation and elevated CBS expression. 3.Our data demonstrate that endogenous H(2)S and CO are in synergy with each other in recurrent FS.     

外源一氧化碳对盐胁迫下水稻悬浮细胞死亡的缓解效应

水稻悬浮细胞经NaCl（0～400mmol·L-1）处理后,细胞死亡率随着NaCl浓度的增大和处理时间的延长而上升。50%饱和度的外源一氧化碳（CO）溶液预处理3h可以缓解随后由200mmol·L-1NaCl引起的细胞死亡率上升,CO清除剂血红蛋白（Hb）有逆转CO的保护效应。CO在不同程度上还可以促进超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和抗坏血酸过氧化物酶（APX）活性的上升或相应基因的表达。     

外源一氧化碳对铁胁迫下的离体水稻叶片氧化伤害的缓解作用

不同饱和度的外源CO水溶液预处理离体水稻叶片,可以浓度依赖性地缓解铁胁迫引起的硫代巴比妥酸反应物质（TBARS）含量的上升,并诱导铁蛋白基因表达。此外,50%饱和度的CO水溶液还能不同程度地逆转由于柠檬酸铁胁迫引起的叶中抗坏血酸过氧化物酶（APX）和超氧化物歧化酶（SOD）活性的上升。     

代谢组学在一氧化碳中毒研究的应用和展望

一氧化碳中毒是常见的以中枢神经系统损害为主的全身性疾病。一氧化碳作为一个脂溶性分子,进入细胞内造成组织缺氧。一氧化碳是否可以诱导产生其他特定的生物学效应,还需要我们去研究。代谢组学是继基因组学、转录组学、蛋白质组学后的又一新兴学科,在肿瘤、糖尿病、冠心病、肥胖症、脑卒中等多种临床疾病的相关研究中显示出巨大的潜力。将代谢组学技术应用到一氧化碳中毒研究中,可以加深对一氧化碳中毒发病机制的认识,丰富早期诊断方法,改善治疗效果的监测手段。但代谢组学技术在一氧化碳中毒研究中的应用仍是凤毛麟角,我们在此对代谢组学在一氧化碳中毒研究中应用及前景作一展望。     

Carbon Monoxide： A Novel Antioxidant Against Oxidative Stress in Wheat Seedling Leaves

Carbon monoxide （CO）, an endogenous signaling molecule in animals, also provides potent cytoprotective effects including attenuation of lung lipid peroxidation induced by oxidant in the mouse. Our recent work demonstrated that 0.01 μmol/L hematin （a CO donor） treatment of wheat plants alleviated salt-induced oxidative damage in seedling leaves. In this report, we further discovered that hematin pretreatment （≤ 0.1 μmol/L） could delay wheat leaf chlorophyll loss mediated by further treatment of H202 and paraquat, two reactive oxygen species （ROS） sources, in dose-and even time-dependent manners. Also, compared with the control samples, seedling leaves pretreated with 0.01 or 0.1 μmol/L hematin for 24 h exhibited lower levels of H2O2 and lipid peroxidation, as well as higher contents of chlorophyll and activities of antioxidant enzymes. Such beneficial effects exerted by hematin were mimicked by the pretreatment of antioxidant butylated hydroxytoluene （BHT）, and differentially reversed when CO scavenger hemoglobin （Hb）, or CO specific synthetic inhibitor ZnPPIX was added, respectively. Taken together, the results presented In this paper directly illustrate for the first time that CO is able to strongly protect plants from oxidative damage caused by the overproduction of ROS, and strengthens the evidence that CO is a potent antioxidant in various abiotic and biotic stresses, as similar results have been shown in animal tissues.     

外源CO和NO对水稻种子萌发过程中干旱胁迫损伤的缓解效应

选用水稻品种‘Ⅱ优128’种子为材料,以1.0μmol.L-1高铁血红素(Hematin,H)和200μmol.L-1硝普钠(sodium nitroprusside,SNP)分别作为CO和NO供体,采用PEG-6000模拟干旱胁迫,研究外源CO和NO对干旱胁迫下水稻种子萌发和萌发过程中抗氧化能力的影响。结果表明:高铁血红素和硝普钠处理可以显著提高干旱胁迫下水稻种子的发芽率、芽长和根长;同时显著提高种子淀粉酶活性,显著增加其可溶性糖、可溶性蛋白和脯氨酸含量;还不同程度地诱导增强超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和过氧化物酶(POD)的活性,同时降低质膜相对透性和丙二醛(MDA)含量。研究证实,外源CO和NO可通过调节渗透调节物质含量和保护酶活性来有效缓解干旱胁迫对萌发水稻种子造成的氧化伤害,促进种子萌发生长。     

Carbon Monoxide Alleviates Wheat Seed Germination Inhibition and Counteracts Lipid Peroxidation Mediated by Salinity

Recently In animals, endogenous carbon monoxide （CO）, like nitric oxlde, was implicated as another Important physiological messenger or bioactive molecule. However, little information is known about the physlologlcal roles of CO in the whole plant. In the present study, we report that different concentrations of the 130 donor hematin （0.1, 1.0 and 10.0 μmol/L） alleviated wheat （Tilticum aestivum L. Yangmai 158） seed germination Inhlbltlon caused by 250 mmol/L NaCI stress In a dose-dependent manner. These responses were also proved by the addltion of different gaseous CO aqueous solutions from 0.1% to 100.0% of saturation. Among these treatments, the effect of 1.0 μmol/L hematin and 1.0% saturation of CO aqueous solution were the most obvlous. Furthermore, compared with non-hematin treatment, the degradation of storage reserves In wheat seeds was also accelerated. Time-course analyses showed that application of hematln dose-dependently Increased the activities of superoxide dismutase, catalase, ascorbate peroxidase, and guaiacol peroxidase activities, thus decreasing the lipid peroxidation In germinating wheat seed subjected to salt stress. Meanwhile, the responses of hematin were specific for CO because the addition of the CO scavenger hemoglobln （0.2 g/L） blocked the various actions of 1.0 μmol/L hematin. Taken together, the results of the present study demonstrate that CO, at a low concentration, is able to attenuate the seed germlnation Inhibition produced by salinity stress and counteract the lipid peroxidation in germinating wheat seeds.     

Prebiotic Methylation and the Evolution of Methyl Transfer Reactions in Living Cells

An hypothesis is presented for theprebiotic origin of methyl groups and the evolution ofmethyl transfer reactions in living cells. This hypothesis,described in terms of prebiotic and early biotic chemicalevolution, is based on experimental observations in our laband in those of others, and on the mechanisms of enzymaticmethyl transfer reactions that occur in living cells. Ofparticular interest is our demonstration of the reductivemethylation of ethanolamine and glycine in aqueous solutionby excess formaldehyde. These reactions, involving prebioticcompounds and conditions, are mechanistically analogous tothe de novo origin of methyl groups in modern cellsby reduction of methylene tetrahydrofolate. Furthermore,modern cellular methyl transfers from S-adenosylmethionineto amine nitrogen may involve formaldehyde as anintermediate and subsequent reductive methylation, analogousto the prebiotic chemistry observed herein.     

醒脑静联合高压氧对急性一氧化碳中毒患者脑功能、肝肾功能及血清氧自由基的影响

摘要 目的：探讨醒脑静联合高压氧对急性一氧化碳中毒（ACOP）患者脑功能、肝肾功能及血清氧自由基的影响。方法：选取2017年1月至2020年1月期间我院收治的ACOP患者60例,按照随机数字表法将患者分为对照组（n=30）和研究组（n=30）,在常规治疗的基础上,对照组给予高压氧治疗,研究组给予醒脑静联合高压氧治疗,对比两组疗效、脑功能、肝肾功能、血清氧自由基以及平均苏醒时间、平均住院时间、迟发性脑病发生率。结果：研究组的临床总有效率为93.33%（28/30）,高于对照组的70.00%（21/30）（P<0.05）。两组治疗后天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、血肌酐(Scr)、血尿素氮(BUN)均较治疗前下降,且研究组低于对照组（P<0.05）。两组治疗后丙二醛 （MDA）较治疗前下降,且研究组低于对照组（P<0.05）;两组治疗后超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-PX）均较治疗前升高,且研究组高于对照组（P<0.05）。两组治疗后年龄相关性脑白质改变（ARWMC）分级量表、美国国立卫生研究院卒中量表(NIHSS)评分均较治疗前下降,且研究组低于对照组（P<0.05）;两组治疗后简易精神状态检查量表(MMSE)评分较治疗前升高,且研究组高于对照组（P<0.05）。研究组平均苏醒时间、平均住院时间均短于对照组,迟发性脑病发生率少于对照组（P<0.05）。结论：醒脑静联合高压氧治疗ACOP患者的疗效显著,有助于患者恢复,可有效清除其血清氧自由基,保护其脑功能、肝肾功能,减少迟发性脑病发生率。     

奥拉西坦联合高压氧治疗重度一氧化碳中毒的疗效及对血清LPA、H-FABP及认知功能的影响

目的:探讨奥拉西坦联合高压氧治疗重度一氧化碳中毒的疗效及对血清溶血磷脂酸(LPA)、心型脂肪酸结合蛋白(H-FABP)及认知功能的影响。方法:选择2016年1月-2018年1月我院收治的重度一氧化碳中毒患者90例进行研究,以随机数表法分为观察组(n=48)和对照组(n=42)。对照组给予高压氧治疗,观察组在对照组的基础上加用奥拉西坦治疗。比较两组患者的临床疗效、血清LPA、H-FABP、认知能力、住院时间、迟发性脑病发生率。结果:两组总有效率分别为93.75%、76.19%,差异显著(P0.05);治疗前,两组血清LPA、H-FABP水平无显著性差异;治疗后,两组血清LPA、H-FABP均显著下降,且观察组血清LPA、H-FAB P水平低于对照组,(P0.05);治疗前,两组患者认知功能无显著性差异;治疗后,两组认知功能较治疗前均显著升高(P0.05),且观察组定向力、记忆力、注意力、语言能力水平均明显高于对照组(P0.05);观察组患者住院时间、迟发性脑病发生率均显著低于对照组,差异显著(P0.05)。结论:在重度一氧化碳中毒患者中应用奥拉西坦联合高压氧效果显著,可有效改善患者血清LPA、H-FABP水平及认知功能。     

Alteration in the Postnatal Ontogeny of Cerebellar Norepinephrine Content Following Chronic Prenatal Carbon Monoxide

The postnatal ontogeny of norepinephrine content in the cortex and cerebellum was determined in rats exposed prenatally to a chronic low level of carbon monoxide (150 parts per million). In the cerebellum, norepinephrine concentration and total norepinephrine content among carbon monoxide-exposed rats were consistently elevated over that of control rats from the second through the sixth postnatal weeks. In the cortex, norepinephrine concentration and total norepinephrine content among carbon monoxide-exposed rats did not differ from that of control rats over the same period. These results identify the cerebellum as a region whose postnatal development is altered by prenatal exposure to low levels of carbon monoxide-induced hypoxia.