诱导型一氧化氮合酶在精索静脉曲张大鼠睾丸中的表达

目的：探讨精索静脉曲张大鼠睾丸组织中诱导型一氧化氮合酶(iNOS)的表达与不育的关系。方法：选择30只成年SD大鼠,随机分为精索静脉曲张组20只,假手术组10只,应用免疫组织化学EnVision法检测iNOS在睾丸组织中的表达并测量曲细精管的直径,比较两者之间差异。结果：精索静脉iNOS的表达明显高于假手术组,差异有非常显著性意义,曲张组曲细精管的直径明显小于假手术组,差异有非常显著性意义。结论：精索静脉曲张大鼠睾丸组织中iNOS过度表达是导致不育的原因之一。     

Nitric oxide in liver fibrosis: The role of inducible nitric oxide synthase

The inducible form of nitric oxide synthase (iNOS) is expressed in hepatic cells in pathological conditions. Its induction is involved in the development of liver fibrosis, and thus iNOS could be a therapeutic target for liver fibrosis. This review summarizes the role of iNOS in liver fibrosis, focusing on 1) iNOS biology, 2) iNOS-expressing liver cells, 3) iNOS-related therapeutic strategies, and 4) future directions.     

诱导型一氧化氮合酶与Dahl-盐敏感大鼠动脉血压的调节

目的和方法:为探讨诱导型一氧化氮合酶 (iNOS)在血液动力学调控中的作用,本研究通过慢性血液动力学实验观察了静脉输入诱导型一氧化氮合酶 (iNOS)抑制剂aminogunidine(AG)对大鼠平均动脉压的影响,并测定了一氧化氮 (NO)终产物NO₂及NO₃含量(UNOx)以及iNOS活性。结果:1.iNOS特异抑制剂AG能明显放大高钠引起的Dahl盐敏感大鼠(DS)的血压上升效应;2.高NaCl输入在导致的DS大鼠血压升高的同时,能引起iNOS活性及UNOx的明显升高。结论:iNOS对DS大鼠具有重要的血液动力学调节作用。     

内皮型、诱导型一氧化氮合酶在乳腺癌中的表达

目的 :研究内皮型一氧化氮合酶 (eNOS)、诱导型一氧化氮合酶 (iNOS)在乳癌中表达及与淋巴结转移的关系。方法 :采用免疫组化S P法检测 60例乳癌中eNOS和iNOS的表达。结果 :eNOS和iNOS阳性在乳癌中表达率分别为 75 0 %和71 7%。在淋巴结转移组和无淋巴结转移组中eNOS阳性表达率分别为 66 7%和 83 3 % ,两组间差异无统计学意义 (χ2 =2 2 2 ,P >0 0 5) ,而iNOS在淋巴结转移和无转移组中阳性表达率分别为 53 3 %和 90 0 % ,两组间差异有统计学意义 (χ2 =9 93 ,P <0 0 1 )。结论 :内皮型、诱导型一氧化氮合酶在乳腺癌中高表达 ;iNOS的表达与乳腺癌的淋巴转移相关     

诱导型一氧化氮合酶在糖尿病性阴茎勃起功能障碍大鼠阴茎的表达

目的:探讨诱导型一氧化氮合酶(iNOS)在糖尿病性阴茎勃起功能障碍(ED)发病进程中的可能作用.方法:注射链脲佐菌素建立糖尿病大鼠模型,分别在注射8周和12周后观察阴茎勃起次数,取大鼠阴茎,用ABC免疫组织化学方法检测阴茎iNOS的分布与表达,免疫印迹检测阴茎iNOS蛋白量的变化.结果:糖尿病大鼠的阴茎勃起次数低于对照组,并随病程延长降低;与对照组比较,糖尿病组阴茎内iNOS阳性细胞数和平均光密度、iNOS蛋白量升高,并随病程延长而进行性升高.结论:糖尿病组大鼠阴茎iNOS表达的升高与ED相关.     

诱导型一氧化氮合酶对大鼠胰岛细胞凋亡的影响

目的:探讨细胞因子和诱导型一氧化氮合酶(iN-OS)对体外培养的大鼠胰岛细胞凋亡和功能的影响及其机制。方法:大鼠胰岛细胞体外培养,随机分组,培养液中分别加入细胞因子IL-1β、TNF-α和/或iNOS抑制剂氨基胍,分为空白对照组、细胞因子组、氨基胍组、氨基胍+细胞因子组。检测指标包括:培养液NO水平和组织iNOS、结构型NOS活性,RT-PCR检测胰岛组织中iNOS基因和凋亡相关基因Bax、Bcl-2的表达情况,AO/EB染色检测胰岛存活,胰岛素释放实验检测胰岛功能。结果:与细胞因子IL-1β和TNF-α共同培养后,大鼠胰岛组织中iNOS的表达增强,活性显著提高(38.93±4.72)U/mL,NO水平上升(313.0±35.4)mol/L,而结构型NOS没有变化;同时胰岛促凋亡基因表达上调,抗凋亡基因表达下降,细胞的存活率下降,胰岛素分泌大大减少。加入氨基胍后,随着胰岛组织中iNOS的活性明显受到抑制,胰岛的凋亡程度减轻,存活和胰岛素分泌情况都明显改善。结论:iNOS在细胞因子诱导的胰岛细胞凋亡中起到十分关键的作用,而氨基胍通过抑制iNOS活性,减轻了细胞因子的损害,降低了胰岛凋亡水平,改善胰岛的存活与功能。     

The role of inducible nitric oxide synthase in cocaine-induced locomotor sensitization.

Experimentally naive male Sprague-Dawley rats (weighing 85-110 g) were used to examine the role of inducible nitric oxide synthase (iNOS) in cocaine-induced locomotor sensitization. Repeated administration of cocaine (15 mg/kg, ip) for 7 consecutive days produced locomotor sensitization. Pretreatment with iNOS inhibitors, L-N(6)-(1-iminoethyl) lysine (NIL) or (-)-epigallocatechin gallate (EGCG; 10 mg/kg, ip), 30 min before cocaine (15 mg/kg, ip) administration totally blocked the development of cocaine-induced locomotor sensitization. Dopamine (DA) receptor binding in the nucleus accumbens (NAC) showed a significant decrease in the density of D(2) receptor and the affinity of D(1) receptor after cocaine treatment. Pretreatment with EGCG or NIL abolished the cocaine-induced changes in these parameters. These results suggest that iNOS may participate in the process of development of locomotor sensitization through the modulation of DA receptors in the NAC.     

Pressure-related activation of inducible nitric oxide synthase

Pressure-related activation of inducible nitric oxide synthase     

The role of inducible nitric oxide synthase following spinal cord injury in rat

Acute spinal cord injury (SCI) is two-step process that first involves the primary mechanical injury and then the secondary injury is induced by various biochemical reactions. Apoptosis is one of secondary SCI mechanisms and it is thought to play an important role for the delayed neuronal injury. The enhanced formation of nitric oxide (NO) via inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of apoptosis in SCI. The level of .iNOS mRNA peaked at 6 hr after SCI and it declined until 72 hr after SCI in a rat model. Double-immunofluorescence staining revealed that iNOS positive cells were stained for ED-1, synaptophysin, GFAP, and oligodendrocyte marker. The terminal deoxynucleotidyl-transferase-mediated dUDP-biotin nick end-labeling (TUNEL) positive cell count was higher for the 72 hr post-SCI group than for the 24 hr post-SCI group. This cell count was also higher going in the caudal direction than in the rostral direction from the epicenter, and especially for the 72 hr group. Treatment with a selective iNOS inhibitor resulted in the reduction of TUNEL-positive cells at the lesion site. These findings suggest that nitric oxide generated by the iNOS of macrophages, neurons, oligodentrocytes, and astrocytes plays an important role for the acute secondary SCI that results from apoptotic cell death.     

Ischemic damage increases nitric oxide production via inducible nitric oxide synthase in the cochlea

The present study was designed to elucidate the dynamic changes of nitric oxide (NO) production in the perilymph and to investigate the immunostaining for inducible nitric oxide synthase (iNOS) in the cochlea for 7 days after transient cochlear ischemia. Moreover, aminoguanidine, which is a selective iNOS inhibitor, was administrated immediately following ischemia and every 24h thereafter for 7 days to investigate whether the production of NO is dependent on the iNOS pathway. Significant increases in the oxidative NO metabolites, nitrite (NO(2)(-)) and nitrate (NO(3)(-)), were measured on day 1 using an in vivo microdialysis and on-line high performance liquid chromatography (HPLC) system. The immunostaining for iNOS was strongly expressed on days 1 and 4 and returned to normal on day 7 after the ischemia. The administration of aminoguanidine reduced the oxidative NO metabolites on day 1 and suppressed the expression of iNOS. These findings suggest that transient ischemia causes a remarkable increase in NO production in the perilymph, which might be attributable to the iNOS pathway.     

Regulation of inducible nitric oxide synthase in post-operative adhesions

BACKGROUND: The deficiency of the inducible nitric oxide synthase (iNOS) substrate, L-arginine (L-Arg), the co-factor tetrahydrobiopterin (H4B) or molecular oxygen may lead to lower NO levels, which enhances the development of adhesion phenotype. METHODS: We utilized high-performance liquid chromatography (HPLC) and immunoprecipitation with nitrotyrosine antibody to determine the levels of H4B, citrulline and protein nitration in fibroblasts established from normal peritoneal and adhesion tissues. RESULTS: The level of H4B was dramatically attenuated in adhesion fibroblasts. The immunoprecipitation with nitrotyrosine antibody revealed higher protein nitration in adhesion compared with normal fibroblasts. There were higher accumulations of citrulline in adhesion fibroblasts as compared with normal fibroblasts. In addition, peritoneal fibroblasts treated with 2% oxygen for 24 h and implanted back into the peritoneal cavity of the rats exhibited marked increase in severity of adhesion as well as extensive distribution involving many sites and organs. CONCLUSIONS: Control of the catalytic activity of iNOS in adhesion fibroblasts may be because of subsaturating amounts of L-Arg and H4B which allow iNOS to generate a combination of reactive oxygen species in addition to NO, thereby influencing NO bioavailability and function.     

一氧化氮/诱导型一氧化氮合酶在动脉粥样硬化过程中的作用

 目的：探讨一氧化氮（NO）/诱导型一氧化氮合酶（iNOS）在动脉粥样硬化（atherosclerosis,AS）过程中的动态变化,分析其对动脉粥样硬化形成过程的影响。方法：将60只SD大鼠随机分成2组：对照组及AS组,每组30只。AS组采用维生素D3腹腔注射联合高脂饲料饲养的方法构建动脉粥样硬化模型。用相关生化方法检测血清各项生化指标：总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、空腹血糖和钙离子,比色法检测血清NO浓度,并对主动脉行HE染色,免疫组化技术检测iNOS蛋白表达,将所得数据进行统计分析,用简单线性相关分析NO与钙离子及动脉粥样硬化指数的相关性。结果：90 d后成功构建了主动脉中膜钙化型动脉粥样硬化模型。血清NO浓度在动脉粥样硬化过程中逐步下降,各组间差异均有统计学意义（均P<0.05）。动脉粥样硬化过程中动脉粥样硬化指数与钙离子呈正相关,与NO呈负相关。在90 d的AS组粥样斑块区免疫组化技术检测到iNOS蛋白表达。结论:在动脉粥样硬化形成过程中,主动脉粥样斑块区iNOS蛋白高表达,但血清NO浓度逐渐降低,NO抗动脉粥样硬化作用减弱。     

Polymorphism of the inducible nitric oxide synthase gene in celiac disease

The aim of this study was to investigate the possible association between the inducible nitric oxide synthase (NOS2) gene promoter polymorphism, CCTTTn microsatellite, with celiac disease susceptibility. We carried out a familial study in which 53 Spanish families were genotyped by a polymerase chain reaction (PCR)-based method combined with fluorescent technology. A transmission disequilibrium test was performed to investigate the transmission pattern of the different CCTTTn alleles from parents to affected offspring. The test did not reach any statistically significant difference because none of the CCTTTn repeats was shown to be significantly transmitted to the affected siblings. Our data suggest that the CCTTTn pentanucleotide microsatellite in the NOS2 gene promoter does not play a major role in celiac disease development.     

葛根素对糖尿病大鼠白内障过程中晶状体诱导型一氧化氮合酶的影响

目的: 观察大鼠糖尿病性白内障(DC)晶状体诱导型一氧化氮合酶(iNOS)基因表达变化及葛根素对DC的治疗作用。方法: 经腹腔注射链脲佐菌素(STZ)复制大鼠DC模型。实验分为STZ组(STZ,45 mg/kg bw,ip)、葛根素组(STZ+葛根素,140 mg/kg bw ip)和对照组(等量生理盐水,ip),分别于实验第20、40、60 d摘取大鼠晶状体,用逆转录聚合酶链反应(RT-PCR)、蛋白印迹(Western blot)和生化方法检测晶状体iNOS mRNA和蛋白表达及一氧化氮(NO)含量、一氧化氮合酶(NOS)活性变化,观察晶状体损伤的宏观和微观病理变化。 结果:对照组大鼠晶状体透明,iNOS mRNA未见明显表达,蛋白呈微弱表达,NOS活性较低,NO含量较少。在DC形成过程中,晶状体出现混浊、晶状体上皮细胞(LEC)有明显病变,并随病程延长而加重;晶状体iNOS mRNA和蛋白表达明显上调,NOS活性增强、NO生成增加,并呈现时间依赖性。用药40-60 d时葛根素组前述晶状体病理变化轻于STZ组,iNOS mRNA和蛋白表达明显低于STZ组,NOS活性及NO 生成低于STZ组。结论: 在大鼠DC形成过程中晶状体iNOS 基因表达上调、NO含量增加;葛根素可减轻晶状体损伤,机制可能与抑制iNOS 基因表达、减少NO生成有关。