一氧化碳在肝脏缺血/再灌注及缺血预处理中的作用探讨

目的 :观察肝脏缺血 /再灌注 (I/R)及缺血预处理 (IPC)之后一氧化碳 (CO)水平的变化 ,初步探讨内源性一氧化碳在此过程中的作用。方法 :制作大鼠肝脏缺血预处理及缺血 /再灌注 (I/R)模型 ,利用分光光度计测定其血浆一氧化碳水平。同时观测有关的肝功能指标 ,包括血浆丙氨酸转移酶 (ALT)、天冬氨酸转移酶(AST)、乳酸脱氢酶 (LDH)及肝脏组织学变化等。结果 :与缺血 /再灌注组相比 ,肝脏缺血预处理组的ALT ,AST及LDH水平明显降低 (P <0 .0 5 ) ,血浆一氧化碳水平明显升高 (P <0 .0 5 ) ,肝脏组织学损害亦较轻。结论 :肝脏缺血预处理之后一氧化碳水平明显上升。内源性一氧化碳可能参与了肝脏缺血预处理的保护作用。     

EVIDENCE OF INCREASED ENDOGENOUS CARBON MONOXIDE PRODUCTION IN NEWBORN RAT ENDOTOXICOSIS

INTRODUCTIONJram-negativesepsisandsepticshockinneonateshaveahighincidenceandmortalityinspiteofmedicaladvances.Althoughtheroleofanumberofcytokines,suchastumornecrosisfactor(TNF),interleukin-1(IL-1),interleukin-6(lL-6),andendothelium-depen-dentrelaxingfactor(EDRF)andnitricoxide(NO),inmediatingthehemodynamicandmetabolicderangementofthisconditionisbecomingclear,thepathogenesisofsepsisandsepticshockisstillnotentirelyunderstood(l).Inrecentyears,biomedicalinterestinendogenouscarbonmonoxide(…     

内源性一氧化碳在肝脏缺血预处理保护机制的实验研究

目的 :研究内源性一氧化碳 (CO)在大鼠肝脏缺血预处理中的保护作用机制。方法 :2 4只Wistar雄性大鼠 ,随机分 3组 :A组缺血再灌注 (I/R) ,B组缺血预处理 (IPC)后行I/R及C组甲基蓝 IPC后行I/R ,比较 3组血浆内源性CO及环 - 1-磷酸鸟苷 (cGMP)的水平。结果 :B组血浆CO水平显著升高 ,cGMP水平亦显著升高 ,血浆AST、ALT水平降低 ;肝组织病理检查发现肝缺血再灌注损伤减轻。C组血浆CO水平较其它两组都高 ,cGMP水平较其它两组都低 ,而ALT、AST水平升高 ;肝组织病理检查发现肝损伤加重。结论 :内源性CO以CO/cGMP信号转导通路参与了肝脏缺血预处理的保护作用。     

内源性一氧化碳与一氧化氮在高血压发病中的相互作用

目的：研究一氧化氮合酶（ｎｉｔｒｉｃ ｏｘｉｄｅ ｓｙｎｔｈａｓｅ, ＮＯＳ）／一氧化氮（ｎｉｃｔｒｉｃ ｏｘｉｄｅ, ＮＯ） 系统和血红素加氧酶（ｈｅｍｅ ｏｘｙｇｅｎａｓｅ,ＨＯ）／一氧化碳（ｃａｒｂｏｎ ｍｏｎｏｘｉｄｅ,ＣＯ）系统在高血压发生机制中的作用及其相互关系。方法：采用ＮＯＳ抑制剂诱导大鼠高血压模型,观察大鼠动脉血压,主动脉组织ＮＯＳ、ＨＯ 活性和ＣＯ 产生释放的变化。结果：大鼠在注射ＮＯＳ抑制剂———左旋硝基精氨酸（ＮＧｎｉｔｒｉｃＬａｒｇｉｎｉｎｅ, ＬＮＮＡ）后第４ 周血压明显增高,同时ＨＯ活性和ＨｂＣＯ形成分别增加２８ ．４％ 和３１ ．１ ％ （ 均为Ｐ＜ ０ ．０１）,血浆和主动脉平滑肌ｃＧＭＰ含量明显增加。同时注射ＨＯ 底物ＨＬＬ和ＬＮＮＡ时,４ 周内血压无明显改变,而ＨＯ活性、ＨｂＣＯ的形成、血浆和主动脉平滑肌ｃＧＭＰ含量比单纯ＬＮＮＡ组增加更明显。结果表明在ＮＯＳ抑制剂诱导的大鼠高血压形成过程中,内源性ＨＯ／ＣＯ 系统可呈代偿性上调状态;应用ＨＯ 底物可诱导ＨＯ活性和ＣＯ 的生成增加,对ＮＯＳ抑制剂所诱导的高血压有防止作用。结论：内源性ＣＯ和ＮＯ都参与血管张力的调节,两者在高血压发生发展     

ROLE OF ENDOGENOUS CARBON MONOXIDE IN ENDOTOXIN SHOCK

Objective. To study the role of endogenous carbon monoxide (CO) in endotoxin shock. Methods. The changes of CO levels and the effects of zinc protoporphyrin IX (ZnPP), an inhibitor of hemeoxygenase (HO), in endotoxin shock and the efficacy of heroin, an inducer of HO were investigated. Results. The plasma CO levels were found to be significantly increased during the comse of endotoxin shock. Injection of ZnPP was shown to abrogate the endotoxin-induced hypotension and metabolic derangements markedly. Administration of hemin to healthy rabbits revealed the hypotension and metabolic derangements similar to the animsls given endotoxin. Conclusion. CO is a newly found endogenously produced mediator which may play an important role in the pathogenesis of endotoxin shock.     

Existence of Heme Oxygenase-carbon Monoxide-cyclic Guanosine Monophosphate Pathway in Human Trabecular Meshwork Cells In Vitro

To confirm the existence of heme oxygenase (HO)-carbon monoxide (CO)- cyclic guanosine monophosphate (cGMP) pathway in the cultured human trabecular meshwork cells (HT-MCs) in vitro, and to evaluate the inductive role of heroin on this pathway, HTMCs of the third to fourth generation were cultured in vitro. Reverse transcripase-polymerase chain reaction (RT-PCR) was employed for detection of HO-1 and HO-2 mRNA. Immunohistochemical staining was used to detect HO-1 and HO-2 proteins. Hemin was added into the culture solution. The HO-1 mRNA levels were quantified by RT-PCR. The relative amount of carbon monoxide released into the media was measured with the quantifying carbon monoxide hemoglobin (HbCO) by spectrophotometry.Radioimmunoassay was used to determine changes of cGMP in HTMCs. The results showed that cultured cells had the specific characteristics of HTMCs. Both HO-1 and HO-2 genes were expressed in HTMCs, as well as HO-1 and HO-2 proteins in HTMCs. Hemin induced HO-1 mRNA,HbCO and cGMP in a dose-dependent manner. In conclusion, HO-CO-cGMP pathway exists in the cultured HTMCs and can be induced by hemin. Pharmacological stimulation of HO-CO-cGMP pathway may constitute a novel therapeutic approach to rescuing glaucoma.     

内源性一氧化碳在大鼠肝缺血再灌注损伤的机制研究

目的:应用内源性一氧化碳诱导剂,观察内源性一氧化碳在肝缺血再灌注损伤中的作用机制。方法:72只SD大鼠随机分为3组,对照组,生理盐水组,氯化血红素组。建立肝缺血再灌注模型后,即刻经尾静脉分别注入生理盐水和氯化血红素。于再灌注后不同时间点处死动物,测量血清中CO ,ET的水平,及肝组织的病理变化。结果:生理盐水组与氯化血红素组CO水平均随着再灌注时间延长而增高,但氯化血红素组增高明显,与生理盐水组比较有显著性差异(P <0 . 0 5)。在生理盐水组ET水平与对照组比较增高明显(P <0. 0 5) ,氯化血红素组ET水平则明显降低,与对照组比较有显著性差异(P <0 . 0 5)。结论:内源性CO对大鼠肝缺血再灌注损伤具有保护作用。     

Existence of heme oxygenase-carbon monoxide-cyclic guanosine monophosphate pathway in human trabecular meshwork cells in vitro

Summary To confirm the existence of heme oxygenase (HO)-carbon monoxide (CO)- cyclic guanosine monophosphate (cGMP) pathway in the cultured human trabecular meshwork cells (HTMCs)in vitro, and to evaluate the inductive role of hemin on his pathway, HTMCs of the third to fourth generation were culturedin vitro. Reverse transcipase-polymerase chain reaction (RT-PCR) was employed for detection of HO-1 and HO-2 mRNA. Immunohistochemical staining was used to detect HO-1 and HO-2 proteins. Hemin was added into the culture solution. The HO-1 mRNA levels were quantified by RT-PCR. The relative amount of carbon monoxide released into the media was measured with the quantifying carbon monoxide hemoglobin (HbCO) by spectrophotometry. Radioimmunoassay was used to determine changes of cGMP in HTMCs. The results showed that cultured cells had the specific characteristics of HTMCs. Both HO-1 and HO-2 genes were expressed in HTMCs, as well as HO-1 and HO-2 proteins in HTMCs. Hemin induced HO-1 mRNA, HbCO and cGMP in a dose-dependent manner. In conclusion, HO-CO-cGMP pathway exists in the cultured HTMCs and can be induced by hemin. Pharmacological stimulation of HO-CO-cGMP pathway may constitute a novel therapeutic approach to rescuing glaucoma. LI Tao, male, born in 1976, Doctor in Charge     

ENDOGENOUS HEME OXYGENASE/CARBON MONOXIDE SYSTEM MEDIATES LIPOPOLYSACCHARIDE-INDUCED INTUSSUSCEPTION IN RATS

ＩＮＴＲＯＤＵＣＴＩＯＮ　　Ｉｎｔｕｓｓｕｓｃｅｐｔｉｏｎ(ＩＮ)ｉｓｏｎｅｏｆｔｈｅｃｏｍｍｏｎｅｓｔａｂｄｏｍｉｎａｌｅｍｅｒｇｅｎｃｉｅｓｉｎｐｅｄｉａｔｒｉｃｓｕｒｇｅｒｙ .Ｔｈｅｃｏｍｐｒｅｓｓｉｏｎａｎｄａｎ ｇｕｌａｔｉｏｎｏｆｔｈｅｍｅｓｅｎｔｅｒｉｃｂｌｏｏｄｖｅｓｓｅｌｓｏｆｔｈｅｉｎｖａｇｉｎａｔｅｄｂｏｗｅｌａｎｄｔｈｅｐｒｅｓｓｕｒｅｏｎｔｈｅｂｏｗｅｌｗａｌｌｃａｎｌｅａｄｔｏｎｅｃｒｏ ｓｉｓａｎｄｐｅｒｆｏｒａｔｉｏｎ .Ｔｈｅｉｎｃｉｄｅｎｃｅｉｓ 2 4ｐｅｒ 10 0 0ｌ…     

ENDOGENOUS HEME OXYGENASE/CARBON MONOXIDE SYSTEM MEDIATES LIPOPOLYSACCHARIDE－INDUCED INTUSSUSCEPTION IN RATS

Objectives. To investigate the role of endogenous heme oxygenase (HO)/carbon monoxide (CO) system in regulating the process of intussusception (IN) induced by administration of lipopolysaccharide (LPS) in rats.Methods. IN model of rats were induced by lipopolysaccharide. HO activity was determined by the amount of bilirubin formation which was measured with a double-beam spectrophotometer, and HbCO formation was measured by CO-oximeter.Results. The results showed that LPS (10mg/kg) caused IN in up to 40% of the rats at 6h after treatment of LPS. The incidence of IN were significantly increased by 50% (P＜0.05) and by 83.2%(P＜0.01) in HO substrate(heme-L-lysinate)-treated rats and in exogenous CO-treated rats, respectively; but it was significantly decreased by 41.8%(P＜0.05) after administration of ZnDPBG, an inhibitor of heme oxygenase (HO) activity. Furthermore, LPS increased HO activity, HbCO formation cGMP content within colic smooth muscle and the plasma level of cGMP, and these parameters were significantly elevated by 62.6%(P＜0.01), 40.0%(P＜0.01), 49.3%(P＜0.05) and 38.9%(P＜0.05), respectively, compared with LPS-non-IN rats.Conclusion. It is suggested that endogenous HO/CO system plays an important role in the process of IN induced by LPS, and inhibition of HO activity may decrease the formation of IN.     

肺缺血再灌注损伤时一氧化碳的变化及葛根素对其影响

目的:观察兔肺缺血再灌注损伤时一氧化碳的变化及葛根素对其的影响.方法:30只健康日本大耳白兔随机分成假手术对照组(C组)、肺缺血再灌注组(IR组)和葛根素组(Pur组).复制兔单侧肺缺血再灌注损伤模型,各组在缺血前、缺血1 h、再灌注1 h、3 h和5 h分别抽血,检测一氧化碳血红蛋白(COHb)浓度、环磷酸鸟苷(cGMP)含量.实验结束时取肺组织检测cGMP含量,电镜观察肺组织超微结构的改变.结果:血浆COHb浓度、cGMP含量和肺组织cGMP含量IR组、Pur组明显高于C组,以Pur组为著(P＜0.01).电镜显示IR组有明显的肺超微结构损伤,而Pur组损伤较轻.结论:葛根素可通过提高内源性C0水平,对缺血再灌注损伤肺组织发挥保护作用.     

sGC-cGMP信号通路在CO介导的呼吸节律调节中的作用

目的 探讨可溶性鸟苷酸环化酶(sGC)-环磷酸鸟苷(cGMP)信号通路是否参与一氧化碳(CO)在延髓水平介导的呼吸节律调节.方法 电生理实验分为5组(每组n=8):单纯人工脑脊液(ACSF)对照组、外源性CO组、ODQ(sGC的选择性抑制剂)组、ODQ CO组和二甲基亚砜(DMSO)组,制备SD大鼠离体延髓脑片标本,以舌下神经根节律性自发放电频率(burst frequency,BF)为指标,分别灌流以上药物,观察呼吸节律的变化;并以放射免疫方法检测单纯ACSF对照组、外源性CO组、ODQ组和ODQ CO组给药后脑片cGMP水平的改变(每组n=6).结果 外源性CO可以使BF减慢(P＜0.05),cGMP水平升高(P＜0.05).ODQ使BF增快(P＜0.05),cGMP水平降低(P＜0.05).在灌流ODQ的同时给予CO,BF和cGMP水平均无明显变化(P＞0.05);给药结束后,BF增快(P＜0.05).结论 在延髓水平,sGC-cGMP信号通路在CO介导的呼吸节律调控中具有重要作用.     

围产期窒息新生儿血浆一氧化碳水平的变化及其意义

目的 探讨围产期窒息新生儿一氧化碳（CO）水平的变化。方法 对33例围产期窒息新生儿以及30例健康新生儿血浆CO和一氧化氮（NO）水平进行测定。结果 围产期窒息组的CO和NO水平均显著高于对照组（P＜0．05）;CO和NO水平与围产期窒息后缺血性脑病（HIE）的发生密切相关,围产期窒息后HIE组的CO和NO水平均显著高于围产期窒息后无HIE组和对照组（P＜0．05）。而围产期窒息后无HIE组和对照组之间的CO和NO水平差异无显著性（P＞0．05）。结论 CO作为NO之外的又一个新的内源性介质在围产期窒息中的作用及其临床意义值得深入研究。     

Interrelation between nitric oxide and endothelin-1 in an experimental acute hypoxia in rats and its intervention

ＯｂｊｅｃｔｉｖｅｓＴｏｓｔｕｄｙｔｈｅｉｎｔｅｒｅｌａｔｉｏｎｂｅｔｗｅｅｎｎｉｔｒｉｃｏｘｉｄｅ（ＮＯ）ａｎｄｅｎｄｏｔｈｅｌｉｎ１（ＥＴ１）ｉｎｅｘｐｅｒｉｍｅｎｔａｌａｃｕｔｅｈｙｐｏｘｉｃｒａｔｓ,ａｎｄｔｏｅｖａｌｕａｔｅｔｈｅｍｅｃｈ...     

ENDOGENOUS HEME OXYGENASE／CARBON MONOXIDE SYSTEM MEDIATES LIPOPOLYSACCHARIDE- INDUCED INTUSSUSCEPTION IN RATS

Objectives. To investigate the role of endogenous heme oxygenase (HO)/carbon monoxide (CO) system in regulating the process of intussusception (IN) induced by administration of lipopolysaccharide (LPS) in rats.Methods. IN model of rats were induced by lipopolysaccharide. HO activity was determined by the amount of bilirubin formation which was measured with a double-beam spectrophotometer, and HbCO formation was measured by CO-oximeter.Results. The results showed that LPS (10mg/kg) caused IN in up to 40% of the rats at 6h after treatment of LPS. The incidence of IN were significantly increased by 50% (P＜0.05) and by 83.2%(P＜0.01) in HO substrate(heme-L-lysinate)-treated rats and in exogenous CO-treated rats, respectively; but it was significantly decreased by 41.8%(P＜0.05) after administration of ZnDPBG, an inhibitor of heme oxygenase (HO) activity. Furthermore, LPS increased HO activity, HbCO formation cGMP content within colic smooth muscle and the plasma level of cGMP, and these parameters were significantly elevated by 62.6%(P＜0.01), 40.0%(P＜0.01), 49.3%(P＜0.05) and 38.9%(P＜0.05), respectively, compared with LPS-non-IN rats.Conclusion. It is suggested that endogenous HO/CO system plays an important role in the process of IN induced by LPS, and inhibition of HO activity may decrease the formation of IN.     

单味柴胡及舒肝健脾汤对正常小白鼠血浆、肝脏及丘脑的环核苷酸的影响

本文介绍用疏肝解郁药物柴胡及舒肝健脾汤水煎液,给正常小白鼠灌胃,观察药物对小白鼠血浆、肝脏及丘脑环核苷酸的影响。柴胡煎液组与对照组比较,仅肝脏的 cAMP/cGMP比值降低;舒肝健脾汤组与对照组比较,前者血浆、肝脏和丘脑的 cAMP 及肝脏、丘脑的 cAMP/cGMP比值,均显著降低(P<0.05或<0.01);而cGMP改变不大。     

锌原卟啉对视网膜cGMP影响的研究

目的根据内源性一氧化碳(CO)刺激细胞内可用溶性鸟苷酸环化酶(GC),引起细胞内环磷酸鸟苷(cGMP)浓度升高,而血红素加氧酶(HO)分解血红素产生一氧化碳和胆绿素的原理。采用Ho的选择性抑制剂锌原卟啉作用于视网膜,测定视网膜中cGMP含量变化,了解血红素加氧酶及内源性一氧化碳是否在视网膜中存在及发挥生理作用。方法兔双眼自身对照,实验眼玻璃体注入4mM锌原卟啉0.1ml,对照眼玻璃体注入生理盐水0.1ml,9小时后测定视网膜中cGMP含量。结果实验眼每毫克干视网膜cGMP含量较对照眼明显下降(P<0.01)。结论视网膜中含有血红素加氧酶及内源性一氧化碳,内源性一氧化碳参与视觉形成过程中cGMP的调节,是视网膜中一种可能的新型神经递质。     

Emergent role of gasotransmitters in ischemia-reperfusion injury

ABSTRACT: Nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) are lipid-soluble, endogenously produced gaseous messenger molecules collectively known as gasotransmitters. Over the last several decades, gasotransmitters have emerged as potent cytoprotective mediators in various models of tissue and cellular injury. Specifically, when used at physiological levels, the exogenous and endogenous manipulation of these three gases has been shown to modulate ischemia/reperfusion injury by inducing a number of cytoprotective mechanisms including: induction of vasodilatation, inhibition of apoptosis, modulation of mitochondrial respiration, induction of antioxidants, and inhibition of inflammation. However, while the actions are similar, there are some differences in the mechanisms by which these gasotransmitters induce these effects and the regulatory actions of the enzyme systems can vary depending upon the gas being investigated. Furthermore, there does appear to be some crosstalk between the gases, which can provide synergistic effects and additional regulatory effects. This review article will discuss several models and mechanisms of gas-mediated cytoprotection, as well as provide a brief discussion on the complex interactions between the gasotransmitter systems.     

Extreme but asymptomatic carboxyhemoglobinemia and chronic lung disease

Carboxyhemoglobinemia is a well-known consequence of carbon monoxide exposure from smoking. However, only moderately elevated levels have been reported. We report the case of an asymptomatic man with severe chronic obstructive lung disease and carboxyhemoglobin levels repeatedly in excess of 30% (maximum, 38.0%) due to smoking. The mechanism by which such high levels were attained was primrily a combination of arterial hypoxia and a high carbon monoxide yield from tobacco. For a given level of carbon monoxide exposure, the hypoxic person will attain a higher carboxyhemoglobin level than will a person without hypoxia.