缺血预处理对高原大鼠肝脏缺血/再灌注损伤早期的影响

目的:了解在高原缺血预处理(IPC)对肝脏缺血/再灌注损伤(I/R)早期保护作用及其机制.方法:SD大鼠45只随机分为3组:假手术组、缺血再灌注组、缺血预处理组.各组恢复血流后分别于1,3,6 h取血液标本,检测血清ALT(nkat/L)、丙二醛(MDA,mmol/L)、NO(μmol/L)的含量.结果:缺血预处理组NO的水平明显高于缺血再灌注组(1 h:95.8±10.1 vs 64.2±6.8,P＜0.01;3 h:91.2±9.7 vs 69.5±7.2,P＜0.01;6 h:77.4±8.6 vs 63.7±6.1,P＜0.01),低于假手术组;而ALT(1 h:2257.1±201.7 vs 2912.2±398.4,P＜0.01;3 h:2465.5±243.4 vs 3637.4±441.8,P＜0.01;2545.5±223.4 vs 4027.5±496.8,P＜0.01)、MDA(1 h:25.1±4.3 vs 38.7±7.6,P＜0.01;3 h:27.5±5.4 vs 45.3±8.8,P＜0.01;34.2±6.7 vs 53.2±10.5,P＜0.01)明显低于缺血再灌注组,高于假手术组.结论:在高原缺氧环境下,缺血预处理对大鼠肝脏缺血再灌注损伤有明显保护作用,其机制可能与缺血与预处理抑制肝脏脂质过氧化物的产生,提高内源性NO的产生,改善肝脏的微循环有关.     

CXC趋化因子受体3和其配体在大鼠肝脏缺血再灌注损伤中的表达

目的:探讨CXC趋化因子受体3(CXCR3)及其配体IP-10和Mig在大鼠肝脏缺血/再灌注(I/R)损伤中的表达及作用.方法:32只Wistar大鼠随机分成4组,每组8只.即假手术组,部分肝脏缺血再灌注6,12和24 h组.应用酶联免疫吸附实验(ELISA)法检测肝组织肿瘤坏死因子(TNF)-α水平.应用半定量聚合酶链式反应(RT-PCR)法测定肝组织CXCR3及其配体IP-10,Mig mRNA的表达.同时检测血清丙氨酸转氨酶(ALT)及天冬氨酸转氨酶(AST)的含量.结果:假手术组肝组织中CXCR3,IP-10,Mig mRNA低表达.缺血再灌注各组肝组织中CXCR3和IP-10 mRNA表达水平均明显高于假手术组(CXCR3:0.925±0.109,0.786±0.074,0.606±0.082 vs 0.125±0.028,均P<0.01;IP-10:0.863±0.091,0.680±0.075,0.543±0.284 vs 0.128±0.027,均P<0.01),6 h组高于12 h组(P<0.01),12h组与24h组无明显差别(P>0.05).Mig mRNA水平较假手术组相比,无显著差异(P>0.05).缺血再灌注各组TNF-α水平较假手术组明显升高(154.88±14-35 ng/L,258.88±13.73 ng/L,182.87±10.95 ng/L vs 23.63±4.00 ng/L,均P<0.01),再灌注12 h达高峰.结论:CXCR3及其配体IP-10在肝脏缺血再灌注早期表达上调,在缺血再灌注损伤中起重要的作用.     

预处理对肝脏再灌注损伤大鼠肝组织、血液中NO和ET的影响及意义

目的　探讨预处理对肝脏缺血再灌注损伤大鼠肝组织和血液中一氧化氮 (NO)和内皮素 (ET)含量的影响及意义。方法　建立肝脏 70 %缺血再灌注损伤大鼠模型 ,分为对照组、缺血组、缺血预处理组、L -精氨酸组(L - arg)、Nω-硝基 - N -精氨酸甲酯 (L - NAME)组 ,观察各组肝功能变化 ,检测肝组织和血清中 NO和 ET及透明质酸 (HA)水平。结果　预处理可减轻 NO水平的下降和血浆 ET的升高 ,防止肝功酶的升高 (P<0 .0 5 )。结论　预处理可诱导缺血再灌注损伤大鼠 NO产生增加、ET产生减少 ,进而改善其微循环 ,减少再灌注损伤。     

诱导型一氧化氮合酶在衰老大鼠心肌对缺血再灌注损伤敏感性增加中的作用

目的探讨衰老大鼠心肌组织过氧亚硝基阴离子(ONOO-)的来源及其在衰老大鼠心肌对缺血再灌注损伤敏感性增加中的作用。方法选取雄性成年SD大鼠和衰老SD大鼠,随机分为3组,成年缺血再灌注组(缺血30 min,再灌注24 h)、衰老缺血再灌注组(缺血30 min,再灌注24 h),衰老缺血再灌注+1 400W组,缺血30 min,再灌注24 h,缺血前24 h及再灌注前25 h分别腹腔注射诱导型一氧化氮合酶(iNOS)的特异性阻断剂1 400W。采用Evans blue和TTC双染法检测心梗面积;用ELISA法检测心肌组织硝基酪氨酸(NT)含量;用Western-blot蛋白印迹法检测大鼠心肌组织中iNOS的蛋白表达水平。结果与成年缺血再灌注组相比,衰老缺血再灌注组心梗面积增大(P0.05);心肌组织NT含量较成年缺血再灌注组明显增高(7.29±0.1 vs 4.61±0.1,P0.05);iNOS表达增高(P0.05);与衰老缺血再灌注组比较,衰老缺血再灌注+1 400W组NT含量减少(3.2±0.1 vs 7.29±0.1,P0.05);心肌梗死面积减小。结论衰老大鼠对心肌缺血再灌注损伤的敏感性增加可能与衰老大鼠心脏中iNOS表达升高有关,催化生成大量NO进而生成毒性的ONOO-,从而损伤心肌。     

Na~+/H~+交换泵抑制剂EIPA对大鼠肝脏缺血再灌注损伤的影响

目的探讨Na+/H+交换泵抑制剂EIPA对SD大鼠肝缺血再灌注损伤的影响。方法 30只成年SD大鼠随机分成空白组,缺血再灌注组,EIPA预处理组,每组10只。用Pringle's法建立肝缺血模型。比较各组之间的ALT、AST、肝组织湿/干比、肝组织匀浆内髓过氧化物酶(MPO)活性、肝组织Ca2+浓度、肝组织形态学变化及EIPA对上述指标的影响。结果肝缺血再灌注损伤时,血清转氨酶、肝组织Ca2+浓度、湿/干比、MPO活性均明显升高(P<0.05),肝脏呈现不同程度的病理改变;使用EIPA预处理后,上述指标的异常变化均明显减轻,差异有统计学意义(P<0.05)。结论 EIPA可能通过降低细胞内Ca2+超载减轻肝组织水肿,抑制中性粒细胞活性,从而改善缺血肝组织的能量代谢和肝脏组织微循环,对SD大鼠肝脏缺血再灌注损伤产生保护作用。     

辛伐他汀对脑缺血-再灌注大鼠神经细胞的保护作用

目的探讨辛伐他汀对局灶性脑缺血-再灌注大鼠神经细胞的保护作用及其机制。方法随机将36只大鼠分为3组:即假手术组6只,缺血组15只,辛伐他汀干预组15只。干预组大鼠在模型制备前用辛伐他汀20mg/kg连续灌胃3d,1次/d;假手术组及缺血组用相同体积的等渗盐水连续灌胃3d。采用线栓法制备大鼠局灶性脑缺血-再灌注损伤模型,缺血2h,再灌注4h。采用硝酸盐比色法检测诱导型一氧化氮合酶(iNOS)活性、NO含量;2,3,5-氯化三苯基四氮唑(TTC)染色测定梗死体积;TUNEL染色法检测细胞凋亡情况。结果缺血-再灌注后干预组、缺血组及假手术组血清中NO含量分别为(89.3±3.0)、(124.9±4.6)、(66.5±3.1)μmol/L;iNOS活性分别为(15.8±2.7)、(23.0±2.9)、(11.1±2.5)U/ml;与缺血组比较,辛伐他汀干预能减少NO的含量,降低iNOS的活性(均P<0.01)。缺血组及干预组凋亡细胞数分别为(18.8±3.6)、(13.0±2.9)个/高倍视野,梗死体积分别为(160±10)、(135±11)mm3。结论辛伐他汀干预能减少脑缺血-再灌注损伤大鼠梗死体积及神经细胞凋亡。其机制可能是通过抑制iNOS的活性,降低NO的含量,从而起到神经保护作用。     

地塞米松在肝脏缺血再灌注损伤中作用的研究进展

地塞米松(dexamethasone)是人工合成的肾上腺皮质激素,由于其显著的药理作用和廉价易获得的特性成为众多学者研究的热点.故广泛应用于各科治疗多种疾病,是临床常用药物.一氧化氮(nitric oxide,NO)及诱导型一氧化氮台酶(inducible nitric oxide synthase,iNOS)是体内半衰期极短的体液因子,其生物效应广泛.近几年的研究结果表明,NO及iNOS与缺血再灌注损伤关系密切,参与缺血再灌注损伤的发生、发展、预后等多个过程,成为缺血再灌注损伤预处理一个非常重要的研究领域.肝脏缺血再灌注损伤(hepatic ischemia-reperfu-sionin jury,HIRI)是由于需要阻断肝门的肝脏手术、肝脏移植,失血性休克以及晚期脓毒血症等各种原因导致肝血流中断或不足使肝脏缺血,当恢复血供再灌注后,肝细胞功能代谢障碍及结构破坏反而加重,器官功能进一步恶化的现象.     

银杏天宝对大鼠实验性结肠炎抗氧化作用的影响

目的:在三硝基苯磺酸灌肠诱导大鼠实验性结肠炎模型中,研究银杏天宝(EGB)的治疗作用及其抗氧化损伤作用的机制.方法:应用三硝基苯磺酸(TNBS)/乙醇灌肠制备大鼠实验性结肠炎模型.实验设正常对照组,三硝基苯磺酸模型组,阳性药物对照组(5-ASA group,100 mg/kg),EGB组(200 mg/kg) 4组.观察大鼠肠组织大体形态和组织学评分.生化法检测大鼠肠组织超氧化物歧化酶(SOD),谷胱苷肽过氧化物酶(GSH-Px)活性及丙二醛(MDA),一氧化氮(NO)含量.免疫组化检测肠组织诱导型一氧化氮合酶(iNOS)蛋白的表达.结果:与模型组相比,EGB组结肠组织iNOS表达明显减少,NO、MDA明显降低(iNOS:19.60%±3.17% vs 81.36%±1.71%;NO:9.20±0.81μmol/g vs 14.77±1.34μmol/g;MDA:3.96±0_35 umol/g vs 6.06±0.39 umol/g;P<0.01):SOD、GSH-Px活性明显升高(SOD:32.52±1.82 kU/g vs 21.90±2.22 kU/g;GSH- Px:49.91±2.59 kU/g vs 41.26±2.90 kU/g;P<0.01).EGB能明显减少大鼠实验性结肠炎模型组大体形态和组织学评分(2.10±0.57vs 3.10±0.57:3.50±0.85 vs 4.7±0.82;P<0.01).结论:EGB可能通过抑制氧自由基反应,抗氧化损伤,抑制NO生成,来减轻结肠炎炎症反应.     

脂联素对大鼠心肌缺血再灌注损伤的保护作用

目的 观察脂联素对大鼠心肌缺血再灌注损伤的保护作用并探讨其机制.方法 32只8周龄雄性大鼠随机分为假手术组、缺血再灌注组、地尔硫革组和脂联素组,每组8只.(1)假手术组:只穿线,旷置90 min.(2)缺血再灌注组:先阻断血流30 min,再灌注60 min.(3)地尔硫(革)组和脂联素组:先阻断血流30 min,于再灌注开始时,从鼠尾静脉分别注射地尔硫(革)(3.5 μg·g~(-1)min~(-1))或脂联素(60 ng·g~(-1)·min~(-1)),注射2 min,再灌注60 min.各模型组于再灌注60 min后处死大鼠.测定心肌组织一氧化氮(NO),心肌组织半胱氨酸蛋白酶3(Caspase 3)活性,心肌组织腺苷酸活化蛋白激酶(AMPK)活性,过氧化物酶体增殖物激活受体γ(PPARγ)的含量,同时用透射电镜观察大鼠心肌线粒体结构.结果 (1)缺血再灌注组心肌组织中Caspase 3活性显著高于假手术组[(168.50±30.08)μmol/L比(53.25±11.41)μmol/L,P<0.01],AMPK活性、PPARγ含量均显著低于假手术组[(0.74±0.59)IU/ml比(25.63±4.61)IU/ml,P<0.01;0.1894比0.7949,P<0.01],心肌组织中NO含量显著低于假手术组[(6.359±1.355)μmol/L比(10.396±1.901)μmol.L,P<0.01].(2)脂联素组心肌组织中Caspase 3活性显著低于缺血再灌注组[(88.75±6.92)μmol/L比(168.50±30.08)μmol/L,P<0.01],AMPK活性、PPARγ含量均显著高于缺血再灌注组[(27.22 ±4.76)IU/ml比(0.74±0.59)IU/ml,P<0.01;0.8613比0.1894,P<0.01],心肌组织中NO含量显著高于缺血再灌注组[(15.755±1.045)μmol/L比(6.359±1.355)μmol/L,P<0.01].脂联素可保护急性心肌缺血再灌注过程中大鼠心肌细胞线粒体结构的完整性,上述作用优于地尔硫(革).结论 脂联素对缺血再灌注造成的心肌损伤有一定的保护作用,机制可能与其增加心肌细胞AMPK、PPARγ表达,以及抗心肌细胞凋亡作用有关.     

谷氨酰胺对大鼠肝脏缺血再灌注损伤时肝组织谷胱甘肽含量和Bcl-2、Bax蛋白表达的影响

目的:探讨谷氨酰胺(glutamine,Gln)对大鼠肝脏缺血再灌注损伤(HIRI)时肝组织谷胱甘肽(glutathione,GSH) 含量和细胞凋亡相关基因Bcl-2和Bax蛋白表达的影响．方法:将48只健康♂Wistar大鼠随机分为谷氨酰胺组 (G组)和对照组(C组)．预置中心静脉导管后经此输液通道分别注入谷氨酰胺溶液和生理盐水行预处理 (3 d)．采用Pringle法夹闭肝十二指肠韧带致肝脏缺血 30 min后,去夹恢复血流为再灌注．分别于再灌注后 1、24 h抽血检测ALT的水平,然后快速切取肝组织检测其还原型GSH的含量,切取部分肝组织用于组织病理学检查,并采用S-P免疫组织化学染色方法检测肝组织细胞凋亡相关基Bcl-2和Bax的蛋白表达情况．结果:再灌注后1、24 h,G组血清ALT水平皆显著低于C组(8．3±2．0 μkat／L vs 13．7±5．5 μkat／L,P<0．05; 2．9±2．5 μkat／L vs 9．1±4．3 μkat／L,P<0．01)．肝脏组织GSH的水平:再灌注后1、24 h,G组肝组织GSH水平皆明显高于C组(1216．09±152．78 μg／g vs 856．68± 117．64 μg/g,P<0．01;899．73±57．75 μg/g vs 800．50± 94．79 μg／g,P<0．05)．肝组织损害的病理学改变:G组明显轻于C组．再灌注后1、24 h,G组肝组织Bcl-2蛋白阳性表达率明显高于C组(100．0％ vs 37．5％,P<0．05; 87．5％ vs 25．0％,P<0．05);再灌注后1、24 h,G组肝组织Bax蛋白阳性表达率明显低于C组(25．0％ vs 87．5％,P<0．05;25．0％ vs 87．5％,P<0．05)．结论:Gln对大鼠HIRI具有保护作用,其作用机制可能与维持体内GSH含量和影响肝组织细胞凋亡相关基因 Bcl-2和Bax蛋白的表达有关．     

Nitric Oxide Contributes to Multiorgan Oxidative Stress in Acute Experimental Pancreatitis

Dabrowski A, Gabryelewicz A. Nitric oxide contributes to multiorgan oxidative stress in acute experimental pancreatitis. Scand J Gasteroenterol 1994;29:943-948.

Background: Nitric oxide is a highly reactive free radical gas. The study was undertaken to determine the nitric oxide contribution to oxidative stress in acute experimental pancreatitis induced in Wistar rats. Methods: Acute haemorrhagic pancreatitis was induced in male Wistar rats by means of a retrograde intraductal injection of 5% Na-taurocholate. The rats were treated with the nitric oxide donor, sodium nitroprusside (SNP) (0.25mg/kg), or with JVtu-nitro-L-arginine methyl ester (l-NAME) (10mg/kg), which is an inhibitor of nitric oxide synthase. We measured malondialdehyde and sulphhydryl group concentrations in pancreatic, lung, and liver tissue. Results: In rats with acute pancreatitis treated with SNP, oxidative stress, expressed by malondialdehyde increase and sulphhydryl group depletion, was much more pronounced than in the other groups. In contrast, intensity of the oxidative stress was significantly reduced in rats treated with l-NAME. Conclusion: The data suggest that nitric oxide is partly responsible for oxidative stress in acute haemorrhagic pancreatitis.     

壳聚糖对大鼠动脉粥样硬化的影响及其机制探讨

目的:研究壳聚糖对大鼠动脉粥样硬化斑块及一氧化氮合酶(NOS)的影响。方法:40只Wistar大鼠均分为:A组(正常对照组);B组:饲以高脂饲料(不含维生素D3);C组:一次性给予大鼠维生素D3(30万U/kg体重)肌肉注射,以球囊损伤主动脉内皮和饲以含维生素D3(1.25×106U/kg)的高脂饲料;D组在C组的基础上饲料中加入5%壳聚糖。90 d后检测主动脉动脉粥样硬化斑块形成及NOS的活性。结果:(1)90 d后C组大鼠胸主动脉形成了明显的动脉粥样硬化斑块,而仅饲以高脂饲料的大鼠胸主动脉结构未见改变,D组大鼠胸主动脉未形成动脉粥样硬化斑块;(2)血管中内皮型一氧化合酶(eNOS)后三组较A组均活性下降(P<0.01),而三者之间无统计学差异;(3)诱导型一氧化氮合成酶(iNOS):B组较A组无差异,而C组较A、B两组表达和活性均显著增加(P<0.05~<0.01),较之C组,D组的水平下降(P<0.01),但仍高于A、B组(P<0.01);(4)较之A组,B、C组的TC、TG、LDL-C水平上升(P<0.05~<0.01),D组的较C组下降(P<0.05~<0.01);B、C组的HDL-C水平较A组明显下降(P<0.01)。结论:壳聚糖可通过抑制胆固醇、甘油三酯等的吸收而发挥抗动脉粥样硬化作用,并通过对血脂的作用而间接发挥对NOS的影响。     

川芎嗪后处理对大鼠心肌缺血再灌注损伤的保护作用

目的：观察川芎嗪后处理对大鼠心肌缺血再灌注损伤的保护作用及探讨其可能的作用机制。方法：采用结扎大鼠左冠状动脉前降支方法制备心肌缺血再灌注损伤模型,记录各组心律失常发生情况,测定肌酸激酶（CK）、超氧化物歧化酶（SOD）、丙二醛（MDA）、一氧化氮（NO）、一氧化氮合酶（NOS）含量,HE染色光镜下观察心肌组织形态学改变并秤重检测心肌梗死面积。结果：川芎嗪组的心律失常发生率明显降低,心肌细胞肿胀明显减轻,血中SoD、NO、NOS含量增加,MDA,CK的生成减少。（P〈0．05）。结论：川芎嗪后处理能降低心律失常发生、减少坏死面积,其作用可能与提高sOD、NO、NOs含量,减少MDA生成有关。     

Nifedipine prevents changes in nitric oxide synthase mRNA levels induced by cyclosporine

Cyclosporine toxicity mainly affects kidney and liver function. We have previously shown that cyclosporine nephrotoxicity alters kidney nitric oxide synthase mRNA pattern of expression. To determine if nitric oxide synthase expression changes are mediated directly by cyclosporine or by secondary hemodynamic alterations induced by cyclosporine, we evaluated if these effects are tissue specific and if nifedipine-induced vasodilation prevents these alterations. Uninephrectomized Wistar rats treated for 7 days with olive oil, cyclosporine (30 mg/kg), nifedipine (3 mg/kg), and nifedipine+cyclosporine were studied. In vehicle and cyclosporine groups, the gene expression of the neuronal, inducible, and endothelial nitric oxide synthases in cerebellum, heart, intestine, liver, renal cortex, and medulla was evaluated. The administration of cyclosporine was associated with nephrotoxicity and hepatotoxicity, increased endothelial nitric oxide synthase mRNA levels in renal cortex and liver, and a decrease in inducible nitric oxide synthase and neuronal nitric oxide synthase in renal medulla. The mRNA levels of the 3 nitric oxide synthase isoforms were not affected in any other tissue. Nifedipine did not alter nitric oxide synthase expression in the control group but prevented changes associated with cyclosporine. These results suggest that cyclosporine-induced changes in the pattern of expression of the nitric oxide synthases may be secondary to its hemodynamic effects.     

罗格列酮对胰岛素抵抗大鼠血一氧化氮和内皮素的影响

目的 探讨罗格列酮对胰岛素抵抗大鼠血一氧化氮和内皮素的影响及其可能作用机制。方法 采用高果糖饲料诱导SD大鼠建立胰岛素抵抗模型，并以普通饲料喂养作为对照组，4周后分别用与不用罗格列酮处理对照组和模型组。8周末测定各组收缩压、空腹血糖、血胰岛素、血脂、血清一氧化氮和血浆内皮素的含量及主动脉一氧化氮合酶活性。结果 模型组收缩压、血胰岛素和血浆内皮素均高于对照组；主动脉一氧化氮舍酶活性和一氧化氮含量显著低于对照组，同时出现脂质代谢紊乱。罗格列酮能显著降低模型组收缩压、血胰岛素和血浆内皮素；提高主动脉一氧化氮合酶活性和一氧化氮含量；改善胰岛素抵抗及脂质代谢紊乱，但罗格列酮不影响对照组大鼠上述各项指标。结论 罗格列酮能改善胰岛素抵抗大鼠血管内皮功能，其机制可能是：一方面通过降低血压、提高胰岛素的敏感性、改善脂质代谢紊乱；另一方面通过提高主动脉一氧化氮合酶活性促进主动脉一氧化氮释放，同时抑制内皮素的增加。     

The role of nitric oxide in the inhibition of gastric epithelial proliferation in portal hypertensive rats

BACKGROUND/AIM: Portal hypertension is associated with inhibition of gastric epithelial proliferation and increased gastric nitric oxide synthase activity. Whether the nitric oxide inhibits gastric epithelial proliferation is unclear. METHODS: Portal vein ligation was performed to induce portal hypertension in rats. The rats were treated for 7 days with either vehicle or N(G)-nitro-L-arginine methyl ester (L-NAME) at 5 mg/kg or 25 mg/kg doses (gastric gavage, twice a day). Sham-operated rats treated with vehicle served as controls. Hemodynamic parameters were measured using radiolabeled microspheres in anesthetized animals. Gastric epithelial proliferation was assessed by evaluating the proliferative cell nuclear antigen labeling index. RESULTS: The cardiac index and gastric fundic blood flow were higher, and the gastric fundic proliferative cell nuclear antigen labeling index was lower in the portal hypertensive rats than in the controls. In portal hypertensive rats, the 5 mg/kg dose of L-NAME decreased the cardiac index and increased the gastric fundic proliferative cell nuclear antigen labeling index to levels similar to those found in the controls, but did not affect gastric fundic blood flow significantly. The 25 mg/kg dose of L-NAME further decreased both the cardiac index and the gastric fundic blood flow, but did not affect the gastric proliferative cell nuclear antigen labeling index significantly. CONCLUSIONS: In portal hypertensive rats, the correction of systemic hyperdynamic circulation by NO inhibition is associated with normalization of gastric epithelial proliferation. Excessive nitric oxide may inhibit gastric epithelial proliferation in portal hypertension.     

Nitric oxide induction in a rat model of selective pancreatic ischemia and reperfusion

BACKGROUND/AIMS: Ischemia and reperfusion of the pancreas may be important in aggravating the course of acute pancreatitis. In a rat model of selective pancreatic ischemia and reperfusion, we studied plasma levels of nitric oxide and expression of nitric oxide synthase in the pancrease and lung. METHODOLOGY: Pancreatic ischemia was achieved by occlusion of the 4 main pancreatic arteries for 40 min; this was followed by a 7-hour reperfusion period (group A, 10 rats). Outcome measures were compared with those of animals undergoing a sham operation (group B, 10 rats). RESULTS: Pancreatic damage in group A animals was demonstrated by increased serum alpha-amylase and by macroscopic and microscopic evidence. Total nitric oxide synthase activity in pancrease and lung was higher than in shams [median: 0.73 vs. 0.54 pmol/mg protein/min in the pancreas (P = 0.0082); 1.38 vs. 0.68 pmol/mg protein/min in the lung (P = 0.023)]; this was mainly due to activation of the inducible isoform of the enzyme. There was an associated 58.2% increase in plasma levels of nitric oxide metabolites [from mean 55.0 to 131.6 mumol/L (P < 0.001)]. Immunohistochemistry confirmed expression of inducible nitric oxide synthase and nitric oxide-mediated oxidative damage (nitrotyrosine) in both pancreas and lung. CONCLUSIONS: Ischemia and reperfusion of the pancreas induces pancreatic damage, overexpression of inducible nitric oxide synthase and oxidative damage within the pancreas and lung.     

糖尿病大鼠肾脏一氧化氮系统基因表达的研究

目的 研究糖尿病大鼠肾脏一氧化氮系统基因的表达。方法 观察了１２周ＳＴＺ－糖尿病大鼠肾脏皮质一氧化氮（ＮＯ）含量及一氧化氮合成酶（ＮＯＳ）活力,并应用ＲＴ－ＰＣＲ技术检测了肾脏皮质诱生型一氧化氮合成酶ｍＲＮＡ水平的改变。结果 糖尿病大鼠肾脏皮质ＮＯＳ活性及ｉＮＯＳ ｍＲＮＡ水平明显高于正常对照组（Ｐ〈０．０５）,然而ＮＯ含量却反而下降（Ｐ〈０．０５）。结论 糖尿病大鼠肾脏一氧化氮合成障碍,灭活加速     

Reduced susceptibility to epinephrine-induced arrhythmias in cirrhotic rats: the roles of nitric oxide and endogenous opioid peptides

BACKGROUND/AIMS: The clinical relevance of QT prolongation, the most widely recognized cardiac electrophysiological abnormality of cirrhosis, is still undefined. The aim of this study is to examine the susceptibility of chronic (4-week) bile duct-ligated rats to epinephrine-induced arrhythmias. The roles of nitric oxide and endogenous opioids were also evaluated. METHODS: Sham-operated and cirrhotic rats were treated with daily subcutaneous administrations of normal saline (1 ml/kg/day), L-NAME (a non-selective nitric oxide synthase inhibitor, 3mg/kg/day), and naltrexone (20mg/kg/day) during the fourth week after operation. In order to evaluate the effects of acute nitric oxide synthesis inhibition, additional groups of animals were treated by acute intraperitoneal L-NAME injections (3mg/kg). Arrhythmias were induced by intravenous injections of 10 microg/kg epinephrine. RESULTS: Despite QT prolongation (P<0.001), epinephrine induced fewer arrhythmias in cirrhotic rats compared to sham-operated animals (P<0.05). Chronic, but not acute, L-NAME administration corrected the QT prolongation in cirrhotic rats (P<0.001), and restored the susceptibility of cirrhotic rats to arrhythmias (P<0.05). Naltrexone injection without a significant effect on epinephrine-induced arrhythmias corrected QT interval in cirrhotic rats (P<0.001). CONCLUSIONS: This study shows that despite QT prolongation, cirrhotic animals are resistant against epinephrine-induced arrhythmias. This resistance is mediated by chronic nitric oxide overproduction.