外源性一氧化氮对大鼠肝脏抗氧化物酶和药物代谢酶活性的影响

用亚硝基铁氰化钠(SNP)作为NO生成前体,以 0, 1, 2, 4 和 8 mg·kg^-1 ip 给予大鼠,每日一次,连续 5 d,来研究外源性NO对大鼠肝脏细胞色素 P450, 苯胺羟化酶(AH), 谷胱甘肽S-转移酶(GST)等药物代谢酶和过氧化氢酶(Cat), 谷胱甘肽过氧化物酶(GSH-Px), 超氧化物歧化酶(SOD)等抗氧化物酶活性以及脂质过氧化的体内影响情况. 结果表明外源性NO能明显降低大鼠肝脏SOD, Cat, AH 的活性和细胞色素P450的含量(P<0.05),并且高剂量组还能明显促进脂质过氧化发生(P<0.05), 但对GSH-Px和GST的活性则无明显影响.     

外源性一氧化氮对大鼠抗氧化酶活性的影响

本研究利用亚硝基铁氰化钠作为体外一氧化氮（ＮＯ）前体，研究ＮＯ对大鼠肝Ｓ９中超氧化物岐化酶（ＳＯＤ），过氧化氢酶（ＣＡＴ）、谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）等抗氧化物酶的活性及脂质过氧化（ＬＰＯ）的影响。结果表明：外源性ＮＯ能体外抑制ＣＡＴ和ＳＯＤ活性，并能引起明显的ＬＰＯ，但对ＧＳＨ－Ｐｘ的活性无明显影响。     

一氧化氮供体对成年大鼠脑缺血后海马神经元再生的影响

目的　研究NO是否参与脑缺血后海马神经元再生。方法　血管内栓线法阻塞大脑中动脉 1.5h后再灌注 ,制备局灶脑缺血再灌性模型。脑缺血后 1h海马内输入 10 μLNO供体硝普钠 (0 .1mmol·L- 1)和维生素C(0 .4mmol·L- 1)。于脑缺血后 12 0h ,5 溴 2′ 脱氧尿嘧啶核苷 (BrdU)掺入法测定海马齿状回的细胞扩增。于再灌注后 2 4h测定海马诱导型一氧化氮合酶 (iNOS)活性及NO水平。结果在再灌注后d 8缺血侧海马齿状回的BrdU阳性细胞数比对照侧多大约 5倍 ,硝普钠和维生素C海马内输入显著增加脑缺血诱发的海马齿状回神经细胞扩增。结论　NO对脑缺血诱发海马齿状回神经元再生有重要作用     

大鼠急性胰腺炎血清一氧化氮和超氧化物歧化酶变化的实验研究

目的探讨一氧化氮（NO）和超氧化物歧化酶（SOD）与急性坏死胰腺炎（ANP）之间的关系。方法 36只Wistar鼠随机分为三组：ANP未治疗组,经胆胰管逆行注射5％牛磺胆酸钠,建立大鼠ANP模型后,腹腔内注射等量的生理盐水;ANP治疗组,ANP模型制备后经腹腔注射硝普钠（0.05m g．100g-1）;对照组,开腹仅轻翻胰腺后,腹腔内注射等量的生理盐水。结果 ANP未治疗组血清NO含量3小时后有所下降,明显低于治疗组（P ＜0.05）;血清SOD活性也明显低于治疗组（P＜0.05）。结论 NO在ANP的过程中发挥重要作用,NO供体药物对大鼠ANP实验模型有治疗作用。     

维生素B_5对全饥饿大鼠脑组织脂质过氧化的动态变化及保护作用

目的观察维生素B5(泛酸)对全饥饿大鼠脑脂质过氧化产物丙二醛(MDA)、还原型谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)的动态变化及保护作用。方法以饥饿昆明大鼠为模型,灌胃补充维生素B5,观察大鼠饥饿后不同时期脑MDA、GSH、GSH-Px及SOD的变化。结果饥饿后大鼠脑MDA含量明显升高,补充维生素B5后大鼠脑组织MDA含量在禁食4d与7d较饥饿前无明显升高,与全饥饿对照组比较差异有统计学意义。维生素B5对饥饿大鼠脑SOD,GSH-Px活力无影响,但显著提高GSH水平。结论维生素B5能减轻饥饿对大鼠脑组织氧化应激反应。     

香菇多糖对巨噬细胞一氧化氮和一氧化氮合酶活性的影响

目的研究香菇多糖(LTN)诱导巨噬细胞的一氧化氮(NO)生成和一氧化氮合酶(iNOS)的活性,探讨LTN的免疫调节作用机理.方法采用Griess反应和荧光法测定不同剂量的LTN作用小鼠腹腔巨噬细胞后NO的生成量和iNOS活性.观察mRNA转录抑制剂、蛋白质合成抑制剂和iNOS抑制剂对巨噬细胞NO的生成和iNOS活性的影响.结果LTN能使小鼠腹腔巨噬细胞NO生成增加,iNOS活性增高,并呈作用剂量依赖关系.3种抑制剂均能抑制LTN诱导的小鼠腹腔巨噬细胞N0的生成和iNOS活性.结论LTN能刺激小鼠腹腔巨噬细胞提高iNOS活性和NO的生成.提示LTN的免疫调节作用机制可能与LTN刺激巨噬细胞NO生成有关.     

香菇多糖对巨噬细胞一氧化氮和一氧化氮合酶活性的影响

目的研究香菇多糖(LTN)诱导巨噬细胞的一氧化氮(NO)生成和一氧化氮合酶(iNOS)的活性,探讨LTN的免疫调节作用机理.方法采用Griess反应和荧光法测定不同剂量的LTN作用小鼠腹腔巨噬细胞后NO的生成量和iNOS活性.观察mRNA转录抑制剂、蛋白质合成抑制剂和iNOS抑制剂对巨噬细胞NO的生成和iNOS活性的影响.结果LTN能使小鼠腹腔巨噬细胞NO生成增加,iNOS活性增高,并呈作用剂量依赖关系.3种抑制剂均能抑制LTN诱导的小鼠腹腔巨噬细胞N0的生成和iNOS活性.结论LTN能刺激小鼠腹腔巨噬细胞提高iNOS活性和NO的生成.提示LTN的免疫调节作用机制可能与LTN刺激巨噬细胞NO生成有关.     

碧萝芷对老年大鼠脂质过氧化作用的影响

机体内过量的自由基是造成衰老和许多疾病的原因之一 ,如能有效清除体内过量自由基 ,这对延寿和防病均有重要意义。碧萝芷 (Pycnogenol)主要由低聚前花青素和其他生物类黄酮及有机酸等有生物活性的水溶性成分组成[1] 。国外报道它能有效清除自由基[1 3 ] ,但对老年生物体内产生的自由基能否清除尚未见报道。为了解其在老年机体内清除自由基的能力 ,我们进行了碧萝芷对老年大鼠体内过氧化脂质含量和抗氧化酶活力等影响的研究。1　材料与方法1 1　样品和试剂　碧萝芷 ,从法国沿海松树树皮中提取的棕红色粉末 ,对光敏感 ,具有吸湿性 ,主要成分…     

雄激素对大鼠主动脉一氧化氮合酶/一氧化氮体系的调节

目的：研究雄激素对大鼠主动脉一氧化氮合酶／一氧化氮(NOS／NO)体系的影响，以探讨雄激素对心血管系统的作用。方法：将30只雄性大鼠随机分为三个组，每组10只，去卵巢组(A组)、去卵巢 雄激素组(B组)、假手术组(C组)。正常饮食2个月后处死大鼠，测血清雄激素、主动脉匀浆一氧化氮合酶活性及一氧化氮含量。结果：同假手术组相比。去势大鼠主动脉匀浆NOS活性及NO含量显著降低，在补充适量的雄激素后．主动脉匀浆NOS活性及NO含量显著上升。结论：雄激素可以调节大鼠动脉内一氧化氮合酶／一氧化氮体系，可能是其调节血管张力的作用机制。     

六氯苯对大鼠肝脏线粒体抗氧化物酶同工酶的影响

六氯苯是一种持久性的环境污染物,早期被用作杀菌剂,如今主要作为几种杀虫剂和氯化物产品生产过程中的副产物和杂质进入环境,并广泛残留于人体和各种生物体内[1]。六氯苯毒性作用的主要靶器官是动物的肝脏[2],通过影响动物肝脏的血红素和膜磷脂代谢而引起卟啉血症,甚至肝癌的产生[3-4],但有关六氯苯毒性作用的机制研究很少深入到细胞器水平。据Billi等[5]报道,六氯苯能导致大鼠肝脏细胞脂质过氧化物(MDA)明显增多,进一步研究发现这种现象的产生出现于大鼠肝脏卟啉含量增加之前,这说明在六氯苯毒性作用机制中,活性氧自由基(ROS)扮演着极为…     

中枢应用一氧化氮对大鼠射乳反射的抑制性作用及其作用部位

为判断中枢一氧化氮（NO）对射乳反射的影响及其作用部位，我们以乳内压的变化为指标，观察了脑室注射NO供体硝普钠对授乳大鼠反射性与诱发性射乳的影响。结果发现，NO对吸吮刺激所诱导的反射性射乳具有抑制性作用，但不影响刺激神经垂体所诱发的射乳过程。这些结果提示，中枢NO可能作用于射乳反射中枢内支配催产素神经元的部位，从而对反射性射乳实现抑制．     

Role of nitric oxide in isoprenaline and sodium nitroprusside-induced relaxation in human hand veins

AIMS: Recent reports, largely in animal models, have suggested that either inhibition of nitric oxide (NO) synthase or endothelium removal in arteries inhibits the response to isoprenaline, a beta-adrenoceptor agonist, and also enhances the response to sodium nitroprusside, a nitrovasodilator. This in vivo study was designed to determine whether N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis, influences relaxation of human hand veins mediated by isoprenaline or by sodium nitroprusside. METHODS: Using the dorsal hand vein technique, full dose-response curves to bradykinin (0.27-278 ng min(-1), n=6), isoprenaline (2.12-271 ngmin(-1), n=8) and sodium nitroprusside (0.01-634 ng min(-1) n=7) were generated on separate occasions before and after L-NMMA co-infusion (50 microg min(-1)). RESULTS: In veins preconstricted with the alpha1-adrenoceptor-selective agonist phenylephrine, the three vasodilators induced maximal responses (Emax) of 119+/-35, 72+/-18 and 103+/-17%, respectively. L-NMMA inhibited relaxation to bradykinin by 64% (P=0.014) but did not influence relaxation induced by isoprenaline. The sensitivity to sodium nitroprusside was significantly enhanced by L-NMMA co-infusion (concentration shift of 2.3, P=0.031). CONCLUSIONS; We conclude that in human veins, spontaneously released NO does not play a major role in isoprenaline-induced relaxation. Our results also suggest that the effects of sodium nitroprusside in this vascular bed may be attenuated by endothelium-derived NO.     

一氧化氮对豚鼠胃窦环行肌电活动和收缩运动的影响

目的:在体外研究一氧化氮对豚鼠胃窦环行肌电活动和收缩运动的影响。方法:用常规方法同时记录胃窦肌条的电活动和收缩运动。结果:在豚鼠胃窦环行肌条上,一氧化氮供体硝普钠(0.5μmol·L~(-1))能显著抑制电活动快波和运动。这种抑制作用不受河鲀毒、阿托品、酚妥拉明和普萘洛尔(各1 μmol·L~(-1))的影响(P>0.05),但可被亚甲基蓝(5μmol·L~(-1))和氧合血红蛋白(5μmol·L~(-1))明显减弱(P<0.01)。结论:一氧化氮抑制豚鼠胃窦环行肌电活动和收缩运动。这种抑制效应是通过一氧化氮对平滑肌细胞膜的直接作用和增加细胞内环磷酸鸟苷来实现的。     

一氧化氮在大鼠心肌缺血后处理中的作用

目的:探讨在体条件下,一氧化氮(NO)对缺血后处理心肌保护作用的影响及可能的途径。方法:建立大鼠在体缺血再灌注模型,将24只大鼠随机分为假手术组、缺血再灌注组、缺血后处理组及一氧化氮合酶(NO S)抑制剂NW-L硝-基精氨酸甲酯(L-NAM E)药物干预后处理组(药物干预组)。于再灌注末测定血浆肌钙蛋白I(cT n I),NO,超氧化物歧化酶(SOD)及丙二醛(M DA)的含量,测定心肌组织梗死面积,免疫组化方法观察心肌组织内皮型一氧化氮合酶(eNO S)的表达。结果:与缺血再灌注组及药物干预组相比,缺血后处理组心肌梗死面积明显减少,血浆cT n I,M DA含量降低,血浆NO,SOD含量升高,心肌细胞胞浆内eNO S表达增加。结论:缺血后处理通过eNO S/NO信号通路,抑制脂质过氧化反应,减轻心肌缺血/再灌注损伤。     

Effect of a nitric oxide releasing derivative of paracetamol in a rat model of endotoxaemia

BACKGROUND AND PURPOSE: Nitroparacetamol is a nitric oxide-releasing paracetamol with novel anti-inflammatory properties compared to the parent compound. This study has investigated the anti-inflammatory activity of nitroparacetamol in a model of endotoxaemia in rats to probe the mechanisms underlying this effect. EXPERIMENTAL APPROACH: Nitroparacetamol (92 mg kg(-1)), paracetamol (50 mg kg(-1)) or vehicle were administered to male, Wistar rats 15 min prior to or 3 h after lipopolysaccharide (0.5 mg kg(-1), serotype 0127:B8). Mean arterial pressure and heart rate were measured for 5 h and plasma and organs were then obtained to determine organ dysfunction, inducible nitric oxide synthase and cyclooxygenase-2 expression (lung, liver and kidney tissue) and plasma nitrate/nitrite. In separate experiments, nitroparacetamol, paracetamol or vehicle was administered 1 h before acetylcholine (0.1 microg kg(-1)) or sodium nitroprusside (0.25 microg kg(-1)) to determine if nitroparacetamol desensitizes responses to exogenous/endogenous nitric oxide. KEY RESULTS: Nitroparacetamol prevented but did not reverse the lipopolysaccharide-induced hypotension. There was no effect on heart rate or plasma markers of organ dysfunction. Nitroparacetamol prevented the increased plasma nitrate/nitrite and expression of COX-2 and iNOS, whereas paracetamol exerted partial inhibition of COX-2 in lung alone. Nitroparacetamol also reduced responses to acetylcholine and sodium nitroprusside. CONCLUSIONS AND IMPLICATIONS: NO is the active component of nitroparacetamol in this model of endotoxaemia. Pro-inflammatory processes targeted by nitroparacetamol have been shown to include iNOS/COX-2 induction and possibly vascular soluble guanylyl cyclase. Precise mechanisms underlying the NO effect are unclear but inhibition of cytokine formation may be important.     

硝普钠对老年人充血性心力衰竭患者心功能及NO、LPO和ANF的影响

目的 :观察硝普钠对老年人CHF患者心功能及NO、LPO和ANF的影响。方法 :1 0 0例 60岁以上CHF患者随机分为硝普钠组和硝酸甘油组 ,硝普钠组应用硝普钠 2 0mg,5 %GS1 0 0ml静滴 ,开始剂量为 1 0～ 2 0 μg·min- 1 ,效果不佳时剂量递增 5～ 1 0 μg,最大剂量 <1 0 0 μg·min- 1 ;硝酸甘油组应用硝酸甘油2 0mg,5 %GS 1 0 0ml静滴 ,均为每日 1次 ,疗程 5～ 7d。结果 :硝普钠组总有效率为 96% ,硝酸甘油组为68% ,两组治疗后心率血压下降、LVEF及CO均增加 ,LPO、ANF下降 ,NO水平上升 ,两组比较 ,硝普钠组明显优于硝酸甘油组 ,P <0 .0 1。结论 :硝普钠对老年人CHF疗效显著 ,不良反应较少 ,对常规治疗效果不佳的老年人CHF患者 ,可应用硝普钠治疗     

Anti-atherogenic effect of statins: role of nitric oxide,peroxynitrite and haem oxygenase-1

Background and purpose:

The pleiotropic effects of HMG-CoA inhibitors (statins), which include anti-inflammation, antioxidation and immunomodulation, are not yet fully understood. The present study was designed to elucidate the role of nitric oxide (NO), peroxynitrite (ONOO⁻) and haem oxygenase-1 (HO-1) in the anti-atherogenic effect of statins.

Experimental approach:

Normal and atherosclerotic New Zealand rabbits were treated with atorvastatin or simvastatin in the presence or absence of inhibitors and promoters of endothelial nitric oxide synthase (eNOS) and HO-1. NO and ONOO⁻ released from isolated aortae by calcium ionophore were measured with nanosensors placed 6 ± 2 nm from aortic endothelium. Expression of eNOS and HO-1 protein, HO activity, plasma malondialdehyde (MDA) and vessel wall thickness were also measured.

Key results:

Hypercholesterolaemia decreased eNOS expression by 31 ± 3%, decreased NO (230 ± 16 vs. 433 ± 17 nmol·L⁻¹ control) and increased cytotoxic ONOO⁻ (299 ± 15 vs. 187 ± 11 nmol·L⁻¹ control). The concentration ratio of [NO]/[ONOO⁻] decreased from 2.3 ± 0.1 (normal) to 0.7 ± 0.1 indicating an increase of nitroxidative stress in atherosclerotic endothelium. Expression of HO-1 protein increased by 20 ± 8% in atherosclerosis and further increased (about 30%) after treatment with statins. Statins partially restored the [NO]/[ONOO⁻] balance (1.5 ± 0.1 for atorvastatin and 1.4 ± 0.1 simvastatin), decreased MDA and wall thickening. Promoters of eNOS and HO-1 (L-arginine and haemin) ameliorated the [NO]/[ONOO⁻] ratio while their inhibitors (L-NAME or tin-protoporphyrin) showed no improvement in these ratio.

Conclusions and implications:

Atherosclerosis induced an endothelial [NO]/[ONOO⁻] balance indicative of endothelial dysfunction. Statins showed anti-atherosclerotic effects mediated by HO-1/eNOS, restoring the [NO]/[ONOO⁻] imbalance and reducing lipid peroxidation.     

Effects of leucocyanidines on activities of metabolizing enzymes and antioxidant enzymes

Procyanidolic oligomers (leucocyanidines, LCs) extracted from grape seeds (Vitis vinifera) are known to have antioxidant and antimutagenic activities, and a protective effect against cardiovascular disease. In the present study we examined the influence of LCs on the activities of phase 1 enzymes and conjugation enzymes and on antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Administration of LCs (25, 50, and 100 mg/kg. p.o. for 7 d) markedly decreased the activities of NADPH-cytochrome P450 reductase, P4501A1, P4501A2, and P4503A4, but significantly increased the activities of glutathione S-transferase and phenolsulfotransferase in rat liver. However, the activities of antioxidant enzymes were not affected by LC administration. The inhibition of P450s and increases in phase II enzyme activities indicate a role for LCs as a chemopreventive agent against toxic or carcinogenic metabolites of P450 isozymes.