他汀对NO缺乏性高血压大鼠主动脉重构的作用

目的　观察他汀类药物对NO缺乏性高血压大鼠主动脉重构的作用 ,并探讨其可能作用机制。方法　给予大鼠L NAME(5 0mg·kg-1·d-1,L组 )造成NO缺乏性高血压模型 ,并在该模型上同时给予西立伐他汀 (0 1mg .kg-1·d-1,L +C组 )或辛伐他汀 (辛伐他汀 5mg·kg-1·d-1,L +S组 )干预。 8周后 ,测定主动脉管壁面积 /管腔面积 (W /L)、组织一氧化氮合酶 (NOS)蛋白表达和活性、脂质过氧化 (MDA)水平和血清一氧化氮代谢物 (NOx)水平。结果　对比正常对照组 (C组 ) ,L NAME喂养大鼠出现血压持续升高和主动脉明显重构 ,主动脉壁eNOS ,iNOS蛋白表达及MDA水平显著增高 ,NOS活性低下 ,血清NOx水平明显降低 (P均 <0 0 1) ,然而未对血脂造成明显影响 (P =NS) ;西立伐他汀和辛伐他汀在未降压和降脂的情况下 ,显著减轻主动脉重构 ,降低W /L(P均 <0 0 1) ;显著抑制高血压大鼠主动脉eNOS(P分别 <0 0 5 ,0 0 1)和iNOS过高表达 (P均 <0 0 1) ;同时降低组织MDA含量 ,提高主动脉NOS活性 (P均 <0 0 1) ,但未明显提高血清NOx水平 (P =NS)。结论　他汀在未降脂和降压的情况下 ,减轻NO缺乏性高血压大鼠主动脉重构 ,这可能与其改善NO利用度和减轻氧化损害有关     

他汀对NO缺乏性高血压大鼠主动脉重构的作用

目的观察他汀类药物对NO缺乏性高血压大鼠主动脉重构的作用,并探讨其可能作用机制. 方法给予大鼠L-NAME(50 mg*kg-1*d-1,L组)造成NO缺乏性高血压模型,并在该模型上同时给予西立伐他汀(0.1 mg.kg-1*d-1,L+C组)或辛伐他汀(辛伐他汀5 mg*kg-1*d-1,L+S组)干预.8周后,测定主动脉管壁面积/管腔面积(W/L)、组织一氧化氮合酶(NOS)蛋白表达和活性、脂质过氧化(MDA)水平和血清一氧化氮代谢物(NOx)水平. 结果对比正常对照组(C组),L-NAME喂养大鼠出现血压持续升高和主动脉明显重构,主动脉壁eNOS,iNOS蛋白表达及MDA水平显著增高,NOS活性低下,血清NOx水平明显降低(P均<0.01),然而未对血脂造成明显影响(P=NS);西立伐他汀和辛伐他汀在未降压和降脂的情况下,显著减轻主动脉重构,降低W/L(P均<0.01);显著抑制高血压大鼠主动脉eNOS(P分别<0.05,0.01)和iNOS过高表达(P均<0.01);同时降低组织MDA含量,提高主动脉NOS活性(P均<0.01),但未明显提高血清NOx水平(P=NS).结论他汀在未降脂和降压的情况下,减轻NO缺乏性高血压大鼠主动脉重构,这可能与其改善NO利用度和减轻氧化损害有关.     

葱神清脂软胶囊对非酒精性脂肪肝大鼠氧化损伤的保护作用

[目的]观察葱神清脂软胶囊对大鼠非酒精性脂肪肝(NAFLD)的保护作用,并初步探讨其相关机制.[方法]SD大鼠40只,随机分为正常组、模型组、葱神清脂软胶囊组和易善复组,每组10只.实验4周后观察各组大鼠血浆丙氨酸氨基转移酶(ALT)、天冬氨酸转氨酶(AST)、肝组织中丙二醛(MDA)、过氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、一氧化氮(NO)、一氧化氮合酶(NOS)水平,以及病理组织学的特点.[结果]2个治疗组大鼠血浆ALT、AST水平,肝组织SOD、MDA、GSH-Px、NO和NOS水平与模型组比较,差异均有统计学意义(P<0.01,<0.05),组织学观察表明2治疗组均能明显减轻肝组织脂肪变性.[结论]葱神清脂软胶囊对大鼠NAFLD具有很好的保护作用,其机制可能与对抗脂质过氧化反应,减少自由基的损伤有关.     

天麻酚类成分对脑缺血模型大鼠海马一氧化氮和一氧化氮合酶的影响

目的探讨天麻酚类成分对脑缺血大鼠海马NO和一氧化氮合酶(NOS)的影响。方法采用双侧颈总动脉永久性结扎法,造成大鼠脑缺血模型。造模6周后,SD大鼠40只随机分为5组,假手术组、模型组、尼莫地平组、天麻酚类成分高剂量组(高剂量组)和天麻酚类成分低剂量组(低剂量组),每组8只。给药3周后,比色法检测海马NO含量和NOS活性,免疫印记法检测大鼠海马NOS 3种亚型(nNOS,iNOS,eNOS)的表达。结果与假手术组比较,模型组大鼠海马NO含量、NOS活性及nNOS和iNOS表达明显升高,eNOS表达明显降低;与模型组比较,尼莫地平组和高剂量组大鼠海马NO含量、NOS活性及nNOS和iNOS表达明显降低,eNOS表达明显升高;低剂量组大鼠NOS活性和iNOS表达明显降低,差异有统计学意义(P<0.05,P<0.01)。结论天麻酚类成分对脑缺血大鼠海马NO损伤有保护作用。     

不同HO-1表达水平对糖尿病模型大鼠血管舒张功能及NOS的影响

目的 探讨改变血红素加氧酶-1(HO-1)表达水平对糖尿病(DM)大鼠血管舒张功能的影响及与一氧化氮合酶(NOS)/一氧化氮(NO)的关系.方法 以链脲佐菌素(STZ)诱导DM大鼠模型.SD大鼠分成4组:对照组、DM组、正铁血红素(HO-1诱导剂)组、锌原卟啉(HO-1抑制剂)组.应用离体血管张力检测技术观察胸主动脉舒张功能变化;RT-PCR法及比色法分别检测血管组织和血清中诱生型NOS(iNOS)及内皮型NOS(eNOS)的表达和NO含量.结果 与DM组相比,正铁血红素组血管环对乙酰胆碱舒张百分率有所提高,而锌原卟啉组血管舒张反应继续下降.应用正铁血红素可在提高DM大鼠血管和血清eNOS表达的同时降低iNOS/NO表达;而锌原卟啉组血清中iNOS活性及其在血管组织表达均增高.结论 提高HO-1的表达水平有益于改善DM大鼠血管舒张反应失调,这种保护作用与抑制iNOS/NO的生成、上调eNOS表达水平有关.     

涎腺腺癌组织中VEGF和NOS的表达及意义

血管内皮生长因子(VEGF)是血管生成过程中的关键因子，其过度表达与肿瘤生长、侵袭及转移关系密切。研究发现，催化一氧化氮(NO)生成的关键酶一氧化氮合成酶(NOS)活性的增高与肿瘤血管生成关系密切。笔者检测了涎腺腺癌VEGF、诱导型NOS(iNOS)和内皮型NOS(eNOS)的表达，以观察VEGF、iNOS和eNOS在涎腺腺癌中的表达及其相关性，探讨NO和VEGF的相互作用及其在促肿瘤生长中的作用机制。     

抗氧化剂PZ51对SHRsp血管内皮细胞作用

目的　研究抗氧化剂PZ5 1对SHRsp高血压发展的慢性过程中内皮细胞的作用及可能的机制。方法　 2 2只 8周龄SHRsp大鼠随机分为PZ5 1组和对照组 ,灌胃治疗 6周。用分光光度计测血浆NO、MDA浓度 ;免疫组化检测颈动脉eNOS蛋白表达 ;电镜扫描颈动脉内皮细胞。结果　PZ5 1组较对照组血浆MDA浓度显著降低 (7.88± 1 0 6vs 10 88± 1.73) μmol/L ,P <0 0 0 1、NO浓度显著升高 (4 0 0 2± 9.74vs 2 2 .2 2± 10 0 5 ) μmol/L ,P <0 0 0 1;颈动脉内皮eNOS蛋白表达显著增加 (8.2 5± 2 .36vs 4 .4 6± 3.14 ,P =0 0 2 6 ) ;电镜检查示PZ5 1组血管内皮细胞病变较对照组轻。结论PZ5 1对SHRsp血管内皮有保护作用 ,可能与其升高内皮细胞eNOS表达、增加血浆NO水平、抑制脂质过氧化有关。     

缺氧性肺动脉高压大鼠肺iNOS mRNA及蛋白表达的实验研究

目的 :通过观察慢性缺氧大鼠肺组织诱生型一氧化氮合酶 (iNOS)表达的变化 ,探讨iNOS在肺动脉高压发病中的作用。方法 :运用血清学检验及免疫组织化学斑点杂交等方法观察血一氧化氮(NO)、肺组织iNOSmRNA及蛋白表达的变化。结果 :正常组大鼠NOS表达呈弱阳性 ,慢性缺氧后肺组织iNOSmRNA升高、蛋白NOS表达呈强阳性 ,血一氧化氮水平升高 (P <0 0 1)。结论 :诱生型一氧化氮合酶、一氧化氮的增加与慢性缺氧性肺动脉高压发病有关。     

神经型一氧化氮合酶在冠心病中的研究进展

一氧化氮合酶在冠心病病理进程中有着重要的作用。一氧化氮合酶有3种亚型:神经型一氧化氮合酶(nNOS或NOS 1),内皮型一氧化氮合酶(eNOS或NOS 3),诱导型一氧化氮合酶(iNOS或NOS 2)。过去认为只有eNOS参与调控血管功能,然而最近众多的研究发现,nNOS表达于血管内皮并且在心血管系统内发挥重要作用。nNOS可以产生一氧化氮(NO)和过氧化氢(H2O2)等物质来调节非神经细胞的信号通路。本文将重点探讨nNOS在冠心病中的研究进展。     

NO与肝癌形成

目的研究一氧化氮(NO)在肝癌发生发展的作用。方法用免疫组化的方法对21例肝癌及癌旁组织中的3种一氧化氮合酶(NOS)及血管内皮细胞生长因子(VEGF)的表达进行原位检测和观察,结果紧邻癌细胞的肝硬化组织或慢性肝炎组织iNOS呈强阳性,远离癌组织的肝硬化组织或慢性肝炎组织多呈阴性或弥漫弱阳性;iNOS在周边癌组织及侵入纤维组织中的癌细胞呈阳性,癌组织核心多呈阴性或弥漫弱阳性。VEGF、nNOS的分布与iNOS相似。eNOS主要分布在肝癌细胞小血管壁内皮及其肌层组织。结论 NOS表达与肝组织癌变及肝癌侵润能力有关,与癌组织获得血管形成和转移表型有关。     

一氧化氮与门脉高压性肠病关系的实验研究

目的探讨ＮＯ在门脉高压性肠病发病机理中的作用。方法制作大鼠四氯化碳门脉高压模型。第１２周末，在冰冻切片上进行结肠ＮＡＤＰＨ黄递酶组织化学染色；应用化学发光法测定ＮＯＳ活性；ＲＴ－ＰＣＲ反应测定ＮＯＳｍＲＮＡ表达量。结果（１）ＮＡＤＰＨ黄递酶组化染色：模型组大鼠结肠粘膜下小血管内皮细胞和神经纤维的ＮＯＳ染色强度显著高于正常对照组。而表层上皮细胞ＮＯＳ染色减弱。（２）化学发光法测定ＮＯＳ活性：模型组大鼠结肠粘膜ＮＯＳ活性较正常对照组显著增加，其中ｉＮＯＳ活性增加更为明显。（３）ＲＴ－ＰＣＲ：模型组大鼠结肠粘膜ＮＯ－ＳｍＲＮＡ表达量较正常对照组显著增加。结论ＮＯ可能由于其扩张血管的特性，而参与门脉高压性肠病血管病变的发病过程，并与门脉高压性肠病粘膜病变、可能存在的运动功能异常亦有一定的关系。     

辛伐他汀对非酒精性脂肪性肝病大鼠肝组织纤维化的影响及分子机制

目的 探讨辛伐他汀对非酒精性脂肪性肝病(NAFLD)肝组织纤维化模型及肝星状细胞的作用及其分子机制.方法 ①体内实验应用高脂饮食建立NAFLD肝组织纤维化大鼠模型,并用辛伐他汀干预,RT-PCR法和Western印迹检测大鼠肝组织中内皮型一氧化氮合酶(eNOS)、诱导型NOS(iNOS)和Ⅰ型胶原mRNA和蛋白的表达.②体外实验采用促进脂肪细胞分化的培养基诱导人肝星状细胞株LX-2细胞获得静止表型,分别用转化生长因子β1( TGF-β1)、NOS抑制剂亚硝基左旋精氨酸甲酯(L-NAME)、辛伐他汀、TGF-β1+辛伐他汀、L-NAME+辛伐他汀处理静止型LX-2细胞,RT-PCR法和Western印迹检测各组LX-2细胞中eNOS、iNOS、α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原mRNA及蛋白的变化.结果 ①随造模时间延长,模型组大鼠肝组织eNOS mRNA和蛋白表达逐渐减少,iNOS和Ⅰ型胶原mRNA和蛋白表达逐渐增加,与正常对照组比较差异有统计学意义(P分别＜0.05和0.01).与24周末模型组相比,辛伐他汀干预组大鼠肝组织eNOS mRNA和蛋白的表达分别增加(0.30±0.02比0.24±0.01和0.45±0.04比0.22±0.02,P值均＜0.05),iNOS mRNA和蛋白的表达分别减少,Ⅰ型胶原mRNA和蛋白表达分别减少(P值均＜0.05).模型组大鼠肝组织中eNOS mRNA和蛋白表达与Ⅰ型胶原mRNA和蛋白表达均呈负相关(P值均＜0.01);iNOS mRNA和蛋白表达与Ⅰ型胶原mRNA和蛋白表达均呈正相关(P值均＜0.01).②体外培养LX-2细胞中,L-NAME能抑制LX-2细胞活化,减少eNOS和iNOS的表达,增加α-SMA和Ⅰ型胶原表达,与TGF-β1作用一致;辛伐他汀能直接增加静止型及活化型LX-2细胞中eNOS的表达,减少iNOS的表达,维持其静止表型,抑制其活化.结论 辛伐他汀通过增加LX-2细胞中eNOS表达,减少iNOS表达,减少α-SMA和Ⅰ型胶原生成,抑制或逆转肝纤维化发生和发展.     

替罗非班对大鼠心肌缺血再灌注后无复流及一氧化氮合酶活性和一氧化氮含量的影响

目的研究替罗非班对大鼠心肌缺血再灌注后无复流及一氧化氮合酶(NOS)活性、一氧化氮(NO)含量的影响,探讨替罗非班改善心肌缺血再灌注后无复流的作用机制。方法雄性Wistar大鼠,随机分为假手术组、对照组和替罗非班组。建立急性心肌缺血再灌注无复流模型,用硫黄素S活体染色,观察大鼠心肌无复流范围;伊文斯蓝、氯化三苯基四氮唑(TTC)染色评估大鼠心肌缺血及梗死范围;紫外分光光度计测定缺血再灌注120min时缺血区心肌内皮型一氧化氮合酶(eNOS)、诱导型一氧化氮合酶(iNOS)、总一氧化氮合酶(tNOS)活性及NO含量。结果缺血再灌注后120min,替罗非班组大鼠与对照组大鼠心肌缺血范围相似[(43.13±5.69)%比(39.98±3.75)%,P>0.05],但无复流范围及梗死范围明显小于对照组[(34.36±6.04)%比(52.09±6.89)%,P<0.01;(80.41±8.48)%比(90.13±5.72)%,P<0.05);对照组大鼠心肌的eNOS活性低于假手术组,iNOS、tNOS活性及NO含量高于假手术组(P<0.01);替罗非班组大鼠心肌的iNOS活性及NO含量高于假手术组(P<0.05,P<0.01),eNOS、tNOS活性与假手术组差异无统计学意义。与对照组比较,替罗非班组大鼠心肌的eNOS活性高于对照组(P<0.05),iNOS活性及NO含量低于对照组(P<0.05,P<0.01),tNOS活性较对照组有降低的趋势,但差异无统计学意义。结论大鼠心肌缺血90min再灌注120min可发生无复流现象;替罗非班可缩小无复流及梗死范围,其机制可能与保护内皮功能有关。     

西红花酸对高血脂家兔血管舒张功能的影响及其机制

目的观察西红花酸对高血脂家兔血管舒张功能的影响并探讨其作用机制。方法用高脂饲料复制家兔高血脂模型。分别于第0、2、4、6、8周测定血清一氧化氮含量。8周末测定血清总胆固醇、低密度脂蛋白胆固醇水平。分离胸主动脉，测定其对乙酰胆碱和硝普钠舒血管作用的反应及血管壁一氧化氮舍酶活性和mRNA表达水平，观察高、低剂量（30、15mg／kg）西红花酸对上述指标的影响。结果高血脂家兔胸主动脉对乙酰胆碱诱导的内皮依赖性舒张作用明显减弱，最大舒张度为正常对照组的54％；高、低剂量西红花酸能显著改善其血管内功能，最大舒张度分别为正常对照组的80％和68％；各组家免血管对硝普钠诱导的非内皮依赖性舒张功能无明显变化；高剂量西红花酸能降低血清总胆固醇和低密度脂蛋白胆固醇，两者分别降低了21．6％和20．2％（P〈0．05），而低剂量西红花酸对此没有影响。和高血脂组相比，高、低剂量西红花酸能时间依赖地增加血清一氧化氮含量，第8周时一氧化氮分别增加了72．4％和36．1％。西红花酸能够显著提高血管壁内皮型一氧化氮合酶活性和mRNA表达水平，高、低剂量组内皮型一氧化氮合酶活性分别增加了76．1％和47．8％，内皮型一氧化氮合酶mRNA表达水平分别提高了54．2％和29．8％；而西红花酸对诱导型一氧化氮合酶活性无明显影响。结论西红花酸能显著增加高血脂家兔血清一氧化氮含量，改善血管舒张功能，其机制与提高血管壁内皮型一氧化氮合酶基因表达水平有关。     

Distribution of nitric oxide synthase in normal and cirrhotic human liver

Chronic liver disorders represent a serious health problem, considering that 300 million people worldwide are hepatitis B virus carriers, and 8,000-10,000 patients per year, in the U.S. alone, die as a result of liver failure caused by hepatitis C infection. Nitric oxide synthase (NOS) regulates hepatic vasculature; however, the patterns of expression and activity of NOS proteins in healthy and diseased human livers are unknown. Sections of diseased (n = 42) and control livers (n = 14) were collected during orthotopic liver transplants and partial hepatectomy. The diseased sections included alcoholic cirrhosis, viral hepatitis, cholestasis, acute necrosis, and uncommon pathologies including alpha(1)-anti-trypsin disorder. The endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) were studied by using the citrulline assay, Western immunoblot, immunohistochemistry, and in situ hybridization. The systemic generation of plasma NO metabolites was measured by HPLC. In control livers, Ca(2+)-dependent and -independent NOS activities were identified by Western analysis as eNOS and iNOS, respectively. The eNOS was uniformly distributed in the hepatocytes and also detected in the endothelium of hepatic arteries, terminal hepatic venules, sinusoids, and in biliary epithelium. The iNOS was detected in hepatocytes and localized mainly in the periportal zone of the liver acinus. This pattern of distribution of eNOS and iNOS in normal liver was confirmed by in situ hybridization. In diseased livers, there was a significant increase in Ca(2+)-independent NOS with the corresponding strong appearance of iNOS in the cirrhotic areas. The eNOS was translocated to hepatocyte nuclei. Thus, eNOS and iNOS proteins are differentially expressed in healthy human liver, and this expression is significantly altered in cirrhotic liver disorders.     

枳黄方对急性酒精性肝损伤大鼠肝脂质过氧化水平的影响及其机制研究

目的:观察枳黄方对急性酒精性肝损伤大鼠肝脂质过氧化水平的影响,并探讨其机制。方法:通过酒精灌胃法制造急性酒精性肝损伤大鼠模型,采用HE染色观察肝病理变化;羟胺法检测肝脏SOD活力;TBA法检测肝脏MDA含量;采用RT-PCR技术检测肝脏NADPH氧化酶gp-91phox mRNA的表达量。结果:枳黄方能改善急性酒精性肝损伤之肝脏病理变化;下调肝脏NADPH氧化酶gp-91phox mRNA的表达;显著降低肝脏MDA含量(P<0.05);显著提高肝脏SOD活力(P<0.01)。结论:枳黄方能对抗酒精性肝损伤大鼠肝脏脂质过氧化,这可能与其能降低肝脏NADPH氧化酶gp-91phox mRNA的表达有关。     

Expression of nitric oxide synthase protein and gene in the splanchnic organsof liver cirrhosis and portal hypertensive rats

AIM To investigate the expression of endothelial NO synthase (eNOS), inducible NO synthase (iNOS)protein and eNOS mRNA gene in the splanchnic organs of liver cirrhosis and portal hypertensive rats.METHODS In control and CCl4-induced liver cirrhotic rats, the expression of eNOS and iNOS proteins wasdetected by immunohistochemical method, and eNOS mRNA was detected by in situ hybridization.RESULTS The expression of eNOS protein and eNOS mRNA increased in most organs of the cirrhotic rats,including bronchial and alveolar epithelial cells, renal tubular epithelial cells and mesenchyma, endothelialand adventitial cells of aorta and superior mesenteric artery, whereas no significant increase of iNOS proteinwas found. In the hepatic tissue, NOS protein and eNOS mRNA were present in mesenchymal cells and vesseladventitial cells, no difference was observed in the expression between control and cirrhotic rats.CONCLUSION The expression of NOS varied in region. In splanchnic organs and vasculars there was anincreased expression of eNOS which induced aplanchnic vasodilation and increased the inflow of portal vein,while in the liver tissue and blood vessel showed no increased expression, which may be associated withincreased intrahepatic vascular resistance.     

Remote ischemic preconditioning protects liver ischemia-reperfusion injury by regulating eNOS-NO pathway and liver microRNA expres-sions in fatty liver rats

BACKGROUND: Ischemic preconditioning (IPC) is a strategy to reduce ischemia-reperfusion (I/R) injury. The protective effect of remote ischemic preconditioning (RIPC) on liver I/R injury is not clear. This study aimed to investigate the roles of RIPC in liver I/R in fatty liver rats and the involvement of en-dothelial nitric oxide synthase-nitric oxide (eNOS-NO) path-way and microRNA expressions in this process. METHODS: A total of 32 fatty rats were randomly divided into the sham group, I/R group, RIPC group and RIPC+I/R group. Serum alanine aminotransferase (ALT), aspartate ami-notransferase (AST) and nitric oxide (NO) were measured. Hematoxylin-eosin staining was used to observe histological changes of liver tissues, TUNEL to detect hepatocyte apoptosis, and immunohistochemistry assay to detect heat shock protein 70 (HSP70) expression. Western blotting was used to detect liver inducible NOS (iNOS) and eNOS protein levels and real-time quantitative polymerase chain reaction to detect miR-34a, miR-122 and miR-27b expressions. RESULTS: Compared with the sham and RIPC groups, serum ALT, AST and iNOS in liver tissue were significantly higher in other two groups,while serum NO and eNOS in liver tissue were lower, and varying degrees of edema, degeneration and in-flammatory cell infiltration were found. Cell apoptosis num-ber was slightly lower in the RIPC+I/R group than that in I/R group. Compared with the sham group, HSP70 expressions were significantly increased in other three groups (all P<0.05). Compared with the sham and RIPC groups, elevated miR-34a expressions were found in I/R and RIPC+I/R groups (P<0.05). MiR-122 and miR-27b were found significantly decreased in I/R and RIPC+I/R groups compared with the sham and RIPC groups (all P<0.05). CONCLUSION: RIPC can reduce fatty liver I/R injury by affect-ing the eNOS-NO pathway and liver microRNA expressions.     

Expression of nitric oxide synthase in human gastric carcinoma and its relation to p53, PCNA

AIM: To investigate the expression of NOS in gastric carcinoma, and to explore the relationship between the expression of nitric oxide synthases (NOS) and p53, PCNA, pathological features and clinical staging of gastric cancer. METHODS: The activity of NOS protein was investigated in 85 samples of human gastric carcinoma and 25 samples of normal gastric mucosal tissue by biochemical assay. We then examined the expression of NOS, p53, PCNA in 85 samples of human gastric cancer was examined by immunohistochemistry, and NOS mRNA expression in 85 gastric cancer tissue specimens by In situ hybridization. RESULTS: Biochemical assay showed that the activity of NOS was significantly higher in gastric carcinoma than in normal gastric mucosal tissues (t=0.4161, P＜0.01). Immunohistochemistry revealed that endothelial nitric oxide synthase (eNOS) expressed in all samples of normal gastric mucosa, but only 6 cases of 85 gastric cancer specimens showed weak positive immunohistochemical reactions to eNOS (20%). Inducible nitric oxide synthase (iNOS) was expressed strongly in human gastric carcinoma (81.2%). In situ hybridization analysis showed that iNOS mRNA expression was significantly stronger than eNOS mRNA expression in gastric cancer tissue (X~2 = 10.23, P＜0.01). The expression of iNOS in gastric cancer was associated with differentiation, clinical stages or lymph node metastases (r=0.3426,P＜0.05). However, iNOS expression did not correlate with histological classifications and morphological types. The expression of iNOS was significantly correlated with p53 or PCNA expression (r=0.3612, P＜0.05). The expression of neuronal nitric oxide synthase (nNOS) was not examined by immunohistochemistry and in situ hybridization in gastric cancer specimens and normal gastric mucosa. CONCLUSION: In human gastric cancer, there is an enhanced expression of iNOS, but not of eNOS. NOS promotes the proliferation of tumor cells and plays an important role in gastric cancer spread. Inactivation of antioncogene p53 and overexpression of iNOS might play a synergetic role in the process of carcinogenesis of human gastric carcinoma.