Effects of Lipoprotein-Associated Phospholipase A2 on Arginase/Nitric Oxide Pathway in Hemodialysis Patients

Lipoprotein-associated phospholipase A2 (Lp-PLA2) and arginase are recently described inflammatory biomarkers associated with cardiovascular disease. In this study, we aimed to investigate the possible effects of serum Lp-PLA2 mass levels on arginase/nitric oxide (NO) pathway as a cardiovascular risk marker in hemodialysis (HD) patients. Forty-three HD patients and 15 healthy subjects were included in this study. Lipid profile, high sensitivity C-reactive protein (hs-CRP), albumin, creatinine, body mass index (BMI), Lp-PLA2 and total nitrite levels, and arginase activity were determined in serum samples from patients and control subjects. Lp-PLA2 levels were found to be positively correlated with arginase, triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and age and negatively correlated with high-density lipoprotein-cholesterol and total nitrite levels, while there was no correlation with BMI and hs-CRP, albumin, and creatinine levels in HD patients. We conclude that elevated Lp-PLA2 mass levels may contribute to impaired arginase/NO pathway in HD patients and that increased the arginase activity and Lp-PLA2 mass levels with decreased total nitrite levels seem to be useful biochemical markers in terms of reflecting endothelial dysfunction and associated cardiovascular risks in HD patients.     

iNOS及eNOS mRNA表达在急性坏死性胰腺炎肺损伤中的作用

目的通过观察急性坏死性胰腺炎(acute necrotizing pancreatitis,ANP)大鼠肺组织中诱导型一氧化氮合酶(inducible nitric oxide synthase,i NOS)mRNA和内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)mRNA的表达,探讨内源性NOS在ANP肺损伤中的作用。方法 40只Wistar大鼠随机分为ANP组(n=30)和假手术组(SO组,n=10),采用5%牛磺胆酸钠逆行胆胰管注射法建立大鼠ANP模型。光镜下观察ANP造模后3 h、6 h及12 h时大鼠肺组织病理变化,并应用RT-PCR法检测相应时相肺组织中i NOS及eNOS mRNA的表达水平。结果随着病程延长,ANP组肺组织可见不同程度的充血、水肿、炎性细胞浸润、出血、坏死等病理损害,各时间点其肺损伤评分均明显高于SO组(P0.05),且呈逐渐升高趋势(P0.05)。ANP组3 h、6 h及12 hi NOS和eNOS mRNA的表达水平较SO组均有明显升高(P0.05)。结论肺组织中i NOS及eNOS mRNA的过度表达可能是大鼠ANP肺损伤发生的重要原因之一,这为采用抑制i NOS及eNOS mRNA的表达减轻ANP肺损伤的治疗手段提供了理论依据。     

门静脉高压症大鼠内毒素血症与一氧化氮变化

本研究拟通过测定门脉高压大鼠血浆内毒素和亚硝酸根/硝酸根离子(NO_2~-/NO_3~-)浓度,探讨一氧化氮(NO)在鼠门高压时产生是否过多及其可能机制.雌性SD大鼠分为三组:端侧门腔分流(PCS,n=10),门静脉部分缩窄引起的肝前型门高压(PHT,n=10)和手术对照组(Sham,n=8).模型制备后两周测定门脉压(FPP)并从腹主动脉采集血样,用于测定(1)血浆亚硝酸根/硝酸根离子浓度;(2)血浆内毒素浓度;(3)肝、肾功能.结果显示:血浆内毒素和NO_2~-/NO_3~-水平是PCS>PHT>Sham,且血浆内毒素与NO_2~-/NO_3~-之间呈密切正相关,提示门脉高压时因门体分流和肝功能减退导致血浆内毒素水平升高,刺激NO合成与释放增多.     

ET及NO在糖尿病肢体动脉闭塞症患者外周血中的变化

目的 :探讨内皮素 (ET)和一氧化氮 (NO)在糖尿病肢体动脉闭塞症中的作用机制。 方法 :取糖尿病肢体动脉闭塞症患者 60例 (A组 ) ,分为血瘀型组 (A1组 )和湿热型组 (A2 组 )为观察组 ,并设对照组单纯糖尿病组 (B组 )、闭塞性动脉硬化症组 (C组 )和健康者组 (D组 )各 2 0例 ,所有受检者均取清晨空腹静脉血 ,ET用放免法检测 ,NO用硝酸还原酶法测定。 结果:A1、A2 、B、C组ET水平均高于D组 ,有非常显著性差异 (P <0 0 1) ;A1组和B组NO均高于D组 ,而A2 组和C组NO水平却低于D组。 结论 :ET和NO与糖尿病肢体动脉闭塞症的发病有密切关系     

Increased Salivary Nitric Oxide and G6PD Activity in Refugees with Anxiety and Stress

Anxiety and stress are related to physiological changes in humans. Accumulating evidence suggests a cross‐talk between psychiatric disorders and oxidative stress. The objective of this study was to compare oxidative stress and defensive antioxidant biomarkers in a group of refugees with acute anxiety and stress with a group of local Jordanians. The Hamilton Anxiety Rating Scale (HAM‐A) and the Perceived Stress Scale (PSS) Arabic version were used to assess anxiety and stress respectively. Salivary nitric oxide concentration, glucose‐6‐phosphate dehydrogenase (G6PD) activity and total salivary protein were compared. As expected, refugees showed higher anxiety and stress scores compared with Jordanians. Also, we report a significant increase in salivary nitric oxide and G6PD activity in the refugee group while total protein concentration did not vary between the two groups. This is the first study that demonstrates an increase in nitric oxide and G6PD activity in the saliva of refugees, thus highlighting their potential role as possible biomarkers in anxiety and stress disorders. Copyright © 2015 John Wiley & Sons, Ltd.     

前列腺癌细胞凋亡与iNOS、Bcl-2的表达及意义

目的 :探讨细胞凋亡和诱生型一氧化氮合酶 (iNOS)、Bcl 2蛋白表达在前列腺癌中的意义以及两者之间的关系。　方法 :对 2 4例前列腺癌、15例前列腺增生及 5例正常前列腺组织行原位细胞凋亡检测及iNOS、Bcl 2蛋白免疫组化检测。　结果 :前列腺癌组的细胞凋亡率和iNOS的染色强度均显著高于前列腺增生组及正常前列腺组(P <0 .0 1) ,且Bcl 2蛋白表达阳性者的细胞凋亡率显著低于阴性者 (P <0 .0 1)。　结论 :前列腺癌的细胞凋亡率可反映其恶性程度 ;iNOS的表达与前列腺癌的分化程度无关 ,但与Bcl 2蛋白表达呈负相关 ;Bcl 2蛋白表达与前列腺癌细胞凋亡呈负相关。iNOS与Bcl 2均可通过影响前列腺癌细胞凋亡而在前列腺癌病理发生发展中起作用     

一氧化氮合酶在食蟹猴睾丸及附睾中的表达及意义

目的:探索一氧化氮合酶(NOS)在食蟹猴睾丸及附睾中的表达及意义。方法:运用免疫组化染色法观察NOS在8只猴龄为8岁左右性成熟食蟹猴睾丸及附睾中的分布。结果:①神经元型NOS(nNOS)免疫反应阳性见于睾丸生精小管上皮内各级生精细胞、腔内精子、附睾输出小管上皮、血管内皮细胞。②诱导型NOS(iNOS)免疫反应阳性见于附睾输出小管上皮、腔内精子、管周类肌细胞、血管内皮细胞。③内皮型NOS(eNOS)免疫反应阳性见于睾丸间质细胞、附睾输出小管上皮、腔内精子、管周类肌细胞、血管内皮细胞。结论:NOS广泛表达于性成熟食蟹猴睾丸及附睾组织细胞中,推测其在参与精子发生、成熟及睾丸激素分泌等过程中起到重要作用。     

Hhcy大鼠阴茎海绵体内NOS及CO含量的研究

目的:检测高同型半胱氨酸血症(Hhcy)大鼠阴茎组织内一氧化氮合酶(NOS)和一氧化碳(CO)的含量并探讨其对阴茎勃起功能的影响。方法:取成年雄性Wistar大鼠20只,随机均分为2组:正常对照组和Hhcy组。Hhcy组给予3%高蛋氨酸饲料喂养,正常对照组给予普通饲料喂养,4周后取血,测定血清Hhcy含量;取阴茎海绵体组织、匀浆,测定NOS和CO的含量。结果:Hhcy组血清中同型半胱氨含量[(22.32±1.65)μmol/L]显著高于正常对照组[(4.90±1.73)μmol/L],阴茎组织中的NOS[(6.45±1.12)nmol/(g·min)]和CO[(10.60±0.92)μmol/L]含量明显低于正常对照组[(10.77±0.60)nmol/(g·min)和(13.36±0.44)μmol/L]。结论:给予4周高蛋氨酸饮食的Wistar大鼠能引起Hhcy。Hhcy大鼠阴茎海绵体组织中内源性NOS和CO降低。Hhcy是大鼠阴茎勃起功能障碍的独立危险因素。     

Elevation of Nitric Oxide Metabolites in the Cerebrospinal Fluid of Patients with Moyamoya Disease

Summary  Background. To investigate whether nitric oxide (NO) contributes to formation of abnormal collateral circulation in patients with moyamoya disease.  Methods. Cerebrospinal fluid (CSF) samples were obtained from the subarachnoid space of the Sylvian fissure during combined bypass surgery for moyamoya disease and kept frozen until NO metabolites, nitrate and nitrite, were measured using a Griess method.  Results. Compared with control CSF obtained from 18 patients with hemifacial spasm, unruptured aneurysm, etc., concentrations of NO metabolites in 26 CSF samples of 18 patients with moyamoya disease were significantly higher (mean±SE; 17.6±1.2 vs. 10.5±1.0 μM, p<0.01). In eight patients, the CSF samples from both the first and second operation could be obtained. NO metabolite concentrations (20.5±2.3 μM) in CSF obtained from the first surgery decreased to 15.7±1.8 μM (p<0.01) in CSF obtained from the second, contralateral procedure. The cases of moyamoya disease with greater development of moyamoya vessels at angiographic stage 3 and 4 tended to show higher concentrations of NO metabolites than cases at earlier or later stages with a few moyamoya vessels.  Interpretation. Nitric oxide concentrations in CSF are chronically elevated in moyamoya disease, probably reflecting development of abnormal collateral circulation. i.e. moyamoya vessels. Vascular bypass surgery can reduce abnormal collateral circulation with reduced production of nitric oxide.     

贫铀对大鼠睾丸诱导型一氧化氮合酶基因表达的影响

目的:通过研究贫铀(DU)颗粒气管灌注后大鼠睾丸诱导型一氧化氮合酶(iNOS)基因表达的变化,揭示DU对生殖系统的毒性作用机制。方法:W istar大鼠随机分为气管灌注生理盐水对照组和DU 1、3、5 mg组,每组5只。3个月后提取大鼠睾丸总RNA进行逆转录聚合酶链反应(RT-PCR)。凝胶成像分析系统扫描RT-PCR产物,用内参半定量法分析iNOSmRNA的变化。结果:对照组无iNOSmRNA表达,各染铀组扩增产物电泳条带吸光度A值明显高于对照组(P<0.05),其中3 mg组产物电泳条带A值最高,5 mg组A值明显低于1 mg组和3 mg组(P<0.05)。结论:DU颗粒气管灌注能使大鼠睾丸iNOSmRNA表达水平升高,DU剂量增高到一定程度则使iNOSmRNA表达水平降低,这种变化可能与DU化学毒性和辐射损伤的复合作用有关。     

The Effects of Nitric Oxide Supplementation and Inhibition on Bacterial Translocation in Bile Duct Ligated Rats

Obstructive jaundice promotes bacterial translocation from the gut, but the role of nitric oxide is controversial in this process. We studied the effects of nitric oxide synthase substrate, L-arginine, and nitric oxide synthase inhibitor, NG-nitro-¿-arginine methyl ester, on bacterial translocation in bile duct ligated rats. The animals were randomized into five groups; control, sham, common bile duct ligation alone, nitric oxide inhibition, and nitric oxide supplementation. Obstructive jaundice was performed with common bile duct ligation. ¿-arginine or NG-nitro-¿-arginine methyl ester was injected once daily for 14 days. Blood bilirubin level, liver histology, and bacterial translocation to the mesenteric lymph nodes as well as to the liver were assessed. The ¿-arginine supplemented group had the lowest bacterial translocation rate, but the most prominent hepatic fibrosis. Nitric oxide inhibition increased bacterial translocation to the mesenteric lymph nodes. Therefore, the administration of nitric oxide donor or inhibitor acts as a significant regulatory factor for bacterial translocation in obstructive jaundice.     

急性胰腺炎患者血浆内皮素和一氧化氮水平变化及其意义

目的：了解急性胰腺炎患者血浆内皮素（ＥＴ）和一氧化氮（ＮＯ）与胰腺微循环的关系。方法：采用放免法和反相高效液相色谱法,分别检测血浆总ＥＴ和ＮＯ的稳定代谢产物ＮＯ２＾－／ＮＯ３＾－,以ＮＯ２＾－／ＮＯ３＾－,以ＮＯ２＾－与ＮＯ３＾－之和代表ＮＯ水平。结果：治疗前ＥＴ和ＮＯ均增高,前者显著大于后者,ＥＴ／ＮＯ比值显著增大。治疗后各值随病情好转渐恢复正常。ＥＴ和ＮＯ呈正相关关系。结论：ＥＴ／ＮＯ比值失衡     

聚精丸对弱精子症患者精浆一氧化氮、超氧化物歧化酶的作用机制研究

目的:研究聚精丸治疗弱精子症的可能机制,为寻找其作用机制提供新的线索。方法:选择弱精子症患者34例,给予聚精丸治疗3个月,治疗前后分别作精液常规及精浆一氧化氮(NO)含量和超氧化物歧化酶(SOD)活性测定,观察治疗前后精液常规参数以及NO含量、SOD活性的变化。结果:与治疗前相比,治疗后精液常规参数均有显著性改变(P<0.05或P<0.01);精浆NO值无明显变化(P>0.05);而SOD活性由(95.97±20.75)μg/L下降为(76.14±19.99)μg/L(P<0.05)。弱精子症治疗前精浆NO含量和SOD活性之间呈负相关(r=-0.246,P<0.05)。结论:聚精丸可以显著改善弱精子症患者精子活动率,但聚精丸的良好疗效可能并不体现在精浆NO含量和SOD活性值的改变。     

Donor–Specific Blood Transfusion Inhibits the Allograft Response: Possible Regulation by Nitric Oxide and Prostaglandin E2

We investigated the effective mechanisms of donor–specific hlood transfusion (DST) using a sponge matrix allograft animal model. Sponges were harvested on various days postgrafting, and both the sponge infiltrating cells and sponge exudate fluid (SEF) were collected. DST completely suppressed cytotoxic T lymphocyte activity throughout the postgrafting period. SEF *N = O concentration (measured as nitrite) in DST mice was significantly lower than in ST mice. Conversely, the amount of PGE₂ in the SEF from DST mice was higher than in ST mice. L)ST may induce intragraft suppressor factors (such as PCE₂), resulting in reduced immune activation with suppression of local immune response.     

慢性肾衰竭患者血清一氧化氮水平与中医辨证分型的关系

目的：探讨慢性肾衰竭(CRF)患者血清NO与中医辨证分型的关系。方法：应用化学比色法,测定70例原发性慢性肾炎CRI患者及31例正常人的血清NO3^-／NO2^-变化。结果：(1)与对照组相比,非尿毒症期患者血清NO水平差异无显著性,尿毒症期组血清NO水平显著升高;(2)非尿毒症期患者按中医辨证分组,肝肾阴虚组、脾肾阳虚组血清NO水平较对照组显著降低,肺肾气虚组与对照组相比无统计学意义;(3)尿毒症期患者按中医辨证分组,各组之间无统计学差异。结论：(1)血清NO变化可能是CRI非尿毒症期患者中医辨证分型的基础之一;(2)尿毒症期患者通过测定血清NO3^-／NO2^-反映的NO水平,不能作为中医辨证分型的物质基础。     

Impact of Nitric Oxide Synthase Glu298Asp Polymorphism on the Development of End-Stage Renal Disease in Type 2 Diabetic Egyptian Patients

Abstract

Background: Nitric oxide is an important regulator of renal hemodynamics. This study aimed to investigate the role of endothelial nitric oxide synthase (eNOS) gene polymorphism in type 2 diabetic patients with end-stage renal disease (ESRD) and to elucidate any alteration of nitric oxide synthase (NOS) activity caused by this polymorphism. Methods: The study included 80 patients with type 2 diabetes of >10 years duration (40 with diabetes-derived ESRD, 40 without nephropathy) and 20 healthy controls. Plasma nitrate/nitrite level, and serum NOS activity were measured and eNOS Glu298Asp genotypes were determined. Results: The frequency of Glu/Glu (GG) genotype in diabetics with ESRD was lower than controls. However, the frequency of Asp/Asp (TT) genotype was increased in diabetics with ESRD as compared to those without nephropathy and controls. Diabetics with ESRD had significantly lower nitrate/nitrite level and NOS activity than those without nephropathy. Diabetic patients with TT genotype are at a significant risk for ESRD. Moreover, subjects carrying TT genotype had lower nitrate/nitrite level and NOS activity than those carrying GG genotype. In diabetics with ESRD, creatinine clearance was positively correlated with both nitrate/nitrite level and NOS activity. Conclusions: These results imply that TT genotype of eNOS may be associated with an increased risk of ESRD in Egyptian type 2 diabetics. It could represent a useful genetic marker to identify diabetics at high risk for the development of ESRD. However, larger future prospective studies are required to confirm the role of eNOS gene polymorphism in the progression of diabetic nephropathy to ESRD.     

雷公藤多甙、甲睾酮和壮骨伸筋胶囊对大鼠睾丸一氧化氮合酶的作用

目的通过雷公藤多甙(GTW)、甲睾酮、壮骨伸筋胶囊3种药物对大鼠睾丸间质细胞一氧化氮合酶(NOS)亚型eNOS和nNOS的影响,探讨3种药物对雄性SD大鼠睾丸功能的作用与一氧化氮(NO)的相关性。方法实验分5组,每组9只,每天分别给予各组GTW[10mg/(kg·d)]、甲睾酮[2mg/(kg·d)]、壮骨伸筋胶囊[0.3g/(kg·d)]、蒸馏水加吐温80(对照组I组)和蒸馏水(对照组II),共4周。第5周末,应用免疫组化ABC法观察3种药物对大鼠睾丸间质细胞NOS阳性细胞数目的影响。结果用药后与对照II组相比,GTW组大鼠睾丸间质细胞nNOS和eNOS阳性细胞数明显减少;甲睾酮组nNOS阳性细胞数明显增多,而eNOS变化不大;壮骨伸筋胶囊组eNOS和nNOS阳性细胞数均明显增多。结论雷公藤多甙通过对eNOS和nNOS的抑制而减少NO产生,进而影响生精过程。壮骨伸筋胶囊通过对eNOS和nNOS的促进而增加NO的合成,使其在增强性功能的过程中可能起重要作用。