Aldehyde dehydrogenase 2 partly mediates hypotensive effect of nitrite on l-NAME-induced hypertension in normoxic rat

Nitrite has become a topic of interest in the field of medical research because of its potential therapeutic role as an alternative source of nitric oxide (NO). While the bioconversion of nitrite to NO occurs via either nonenzymatic or enzymatic reduction under acidic or hypoxic conditions, little is known about its conversion to NO under normoxic conditions. Because of a recent report of aldehyde dehydrogenase 2 (ALDH2)-catalyzed glyceryl trinitrate (GTN) vasorelaxation by denitration of GTN to 1,2-glyceryl dinitrate (1,2-GDN) and nitrite, we therefore investigated a catalytic activity of ALDH2 for nitrite reduction and subsequent effect on N^ω-nitro-l-arginine methyl ester (l-NAME)-induced hypertension in normoxic rat. Male Sprague–Dawley rats treated with l-NAME in drinking water for 3 weeks developed hypertension with significantly reduced plasma levels of nitrite and nitrate. The intravenous injection of sodium nitrite lowered the arterial pressure in a dose-dependent manner (17, 50 and 150?μmol/kg). Pretreatment with ALDH2 inhibitors (cyanamide and chloral hydrate) partially inhibited the hypotensive responses to sodium nitrite. In addition, cyanamide significantly delayed the nitrite clearance from plasma and most of the organs examined during the experimental period. These results suggest that ALDH2 may be at least in part involved in nitrite-mediated hypotensive effects and nitrite catalysis in many organs of normoxic rats.     

Emerging role of nitrite in human biology

Nitric oxide (NO) plays a fundamental role in maintaining normal vascular function. NO is produced by endothelial cells and diffuses both into smooth muscle causing vasodilation and into the vessel lumen where the majority of this highly potent gas is rapidly inactivated by dioxygenation reaction with oxyhemoglobin to form nitrate. Diffusional barriers for NO around the erythrocyte and along the endothelium in laminar flowing blood reduce the inactivation reaction of NO by hemoglobin, allowing sufficient NO to escape for vasodilation and also to react in plasma and tissues to form nitrite anions (NO(2)(-)) and NO-modified peptides and proteins (RX-NO). Several recent studies have highlighted the importance of the nitrite anion in human biology. These studies have shown that measurement of plasma nitrite is a sensitive index of constitutive NO synthesis, suggesting that it may be useful as a marker of endothelial function. Additionally, recent evidence suggests that nitrite represents a circulating storage pool of NO and may selectively donate NO to hypoxic vascular beds. The conversion of nitrite to NO requires a reaction with a deoxygenated heme protein, suggesting a novel function of hemoglobin as a deoxygenation-dependent nitrite reductase. This review focuses on the role of nitrite as a circulating NO donor, its potential as an index of NO synthase (NOS) activity and endothelial function, and discusses potential diagnostic and therapeutic applications.     

A tungsten supplemented diet attenuates bacterial translocation in chronic portal hypertensive and cholestatic rats: role of xanthine dehydrogenase and xanthine oxidase

BACKGROUND: Bacterial translocation (BT) plays a major role in the pathophysiological process of spontaneous infections in portal hypertension (PH) and cholestatic jaundice. The major mechanisms promoting BT in experimental animal models are the disruption of the intestinal ecological equilibrium and disruption of the intestinal mucosal barrier. The enzymes xanthine dehydrogenase (XD) and xanthine oxidase (XO) are often implicated as a significant source of oxidants which have a major impact on the impairment of intestinal barrier function. AIM: To investigate the incidence of BT in rats with PH and obstructive jaundice, and to evaluate the impact of XD and XO. METHODS: Animals were subjected to sham laparotomy (SL), PH by calibrated stenosis of the portal vein, and common bile duct ligation (CBDL). They were fed either a standard pellet diet or a tungsten supplemented molybdenum-free diet. Four weeks after the operative procedure, intestinal colonisation and BT to portal vein, vena cava, mesenteric lymph nodes, liver, and spleen were determined. Intestinal XD and XO activity were measured enzymatically and histochemically. RESULTS: Significant (p<0.01) intestinal bacterial overgrowth was present in all PH and CBDL groups compared with the SL group. In normally fed animals after SL, BT occurred in 12%. In PH and after CBDL, the rate of BT increased significantly (p<0.05) to 28% and 54% respectively. In the jejunum of normally fed animals subjected to PH or CBDL, a significant increase in XO was observed (p<0.01). Animals fed a tungsten supplemented diet showed a significant attenuation of BT to 14% in PH and 22% after CBDL (p<0. 05). Tungsten treatment completely suppressed jejunal XD and XO activities. CONCLUSIONS: Significant intestinal bacterial overgrowth, BT, and XD to XO conversion occurred in PH and after CBDL. XD and XO inactivation by a tungsten supplemented molybdenum-free diet significantly reduced the incidence of BT without affecting intestinal bacterial overgrowth. These data strongly support the hypothesis that increased XD to XO conversion may contribute to intestinal barrier failure in PH and after CBDL.     

Microvascular thrombosis models in venules and arterioles in vivo

Platelets are intimately involved in hemostasis and thrombosis. Under physiological conditions, circulating platelets do not interact with microvascular walls. However, in response to microvascular injury, platelet adhesion and subsequent thrombus formation may be observed in venules and arterioles in vivo. Numerous intravital video microscopy techniques have been described to induce and monitor the formation of microvascular thrombi. The mechanisms of microvascular injury vary widely among different models. Some models induce platelet activation with minimal effects on endothelium, others induce endothelial inflammation or injury, while other models lead to thrombus formation associated with endothelial denudation. The molecular mechanisms mediating platelet-vessel wall adhesive interactions differ among various models. In some instances, differences in responses between venules and arterioles are described that cannot be explained solely by hemodynamic factors. Several models for induction of microvascular thrombosis in vivo are outlined in this review, with a focus on the mechanisms of injury and thrombus formation, as well as on differences in responses between venules and arterioles. Recognizing these characteristics should help investigators select an appropriate model for studying microvascular thrombosis in vivo.     

Significance of hepatic xanthine oxidase and uric acid in aged and dietary restricted rats

Xanthine oxidase (XOD), one of the major intracellular sources of superoxide production, is well characterized as a causative factor in ischemia/reperfusion related damage. In the present study, we investigated age-effect on the status of XOD, an enzyme interconvertible with xanthine dehydrogenase (XDH) under oxidative stress. We also examined the modulation of the enzyme using the anti-oxidative action of dietary restriction (DR). We obtained evidence showing XOD activity to be significantly increased by DR, peaking at 24 months, although no progressive, age-related changes were noticed. On the other hand, while XDH activity decreased in ad libitum fed rats with age, DR maintained higher activity levels at 18 and 24 months of age. During aging, the conversion of XDH to XOD was slightly increased, as indicated by the XOD/XDH ratio. One novel finding of the present study is DR’s ability to elevate the uric acid level, which likely augments the anti-oxidative defense system, thereby buffering against oxidatively stressed conditions during aging. Based on what is known about the antioxidative abilities of DR and uric acid, we propose that the high uric acid levels we observed in DR rats may well serve as part of a defense strategy to protect redox balance.     

白藜芦醇预处理对体外大鼠心肌缺血再灌注损伤的保护作用

目的:观察白藜芦醇预处理对体外大鼠缺血再灌注心肌损伤的保护作用及其作用机制。方法:利用Langendorff灌注系统,建立体外大鼠心肌常温全心心肌缺血30min再灌注120min损伤模型。将56只雄性SD大鼠随机分为4组(每组14只):缺血再灌注损伤(IRI)组、白藜芦醇组、Nω硝基L精氨酸甲酯(LNAME)组、氨基胍(AG)组。检测各组的心功能、心肌一氧化氮合酶(NOS)同工酶(NOSi)活性、一氧化氮(NO)的含量、丙二醛的含量、心肌梗死面积以及心肌细胞凋亡指数。结果:与IRI组相比,白藜芦醇组左室发展压(LVDP)、左室压力上升和下降最大变化速率(±dp/dtmax)明显改善(P<0.05或0.01);心肌梗死面积、心肌细胞凋亡指数、心肌丙二醛含量显著降低(P<0.01);心肌NOSi活性和NO含量显著升高(P<0.01)。LNAME组和AG组LVDP和±dp/dtmax显著低于白藜芦醇组(P<0.05或P<0.01);心肌梗死面积、心肌细胞凋亡指数、心肌丙二醛含量显著升高(P<0.01);心肌NOSi活性和NO含量显著降低(P<0.01)。结论:白藜芦醇对体外大鼠IRI具有保护作用,其机制可通过提高心肌NOSi活性,促进NO产生而介导的。     

Magnesium deficiency during pregnancy in rats increases systolic blood pressure and plasma nitrite

We investigated the effect of moderate dietary magnesium (Mg) deficiency, pregnancy, and concurrent L-arginine ingestion on systolic blood pressure (BP), nitric oxide production, serum Mg, and intrauterine growth restriction. Female rats, fed Mg deficient or sufficient diets from weaning, were divided into three groups: (1) nonpregnant, (2) pregnant, and (3) pregnant + 1% L-arginine in the drinking water. The systolic BP, plasma nitrite, serum Mg, and pup weights were determined. Data were analyzed using general linear model analysis of variance. In the pregnant rats, the Mg-deficient group had a significantly higher systolic BP (P =.0275) and plasma nitrite (P =.0244) compared to the Mg-sufficient group. L-Arginine ingestion significantly lowered systolic BP (P <.0001), and increased pup weight (P <.0067). Among the deficient groups, serum Mg was significantly lower (P =.0010) in pregnant rats without L-arginine, but was similar to the nonpregnant state in pregnant Mg-deficient after ingesting L-arginine. Moderate Mg deficiency, during the stress of pregnancy, adversely affected BP, nitric oxide production, and serum Mg. Supplemental L-arginine prevented these negative effects, possibly through a feedback loop by increasing nitric oxide syntheses, which increases cyclic guanosine monophosphate, which then increases free Mg and decreases free calcium. These ionic changes can act to decrease BP and modulate nitric oxide synthesis.     

家兔动脉粥样硬化与血小板源内皮型氧化氮合酶表达的相关性

目的 探讨家兔动脉粥样硬化及斑块形成与血小板源内皮型氧化氮合酶(eNOS)表达的关系. 方法 设立模型组、治疗组和非治疗组及对照组,每组家兔6只.模型组、治疗组和非治疗组每天给予胆固醇饮食,至12周建立家兔动脉粥样硬化模型,建模后继续喂养至24周,同时治疗组服用普伐他汀10 mg/d;非治疗组仅给予普通饮食.实验终点剥离家兔主动脉观察大体和组织病理形态,反转录一聚合酶链式反应(RT-PCR)方法 检测血小板源eNOS/mRNA水平. 结果 模型组和非治疗组均可见明显动脉粥样硬化和(或)斑块形成;主动脉最大脂纹或斑块厚度占整个血管壁厚度的百分比,对照组、模型组、治疗组和非治疗组分别是0.04±0.02、0.82±0.16、0.33±0.18和0.77±0.14,治疗组与非治疗组比较,差异有统计学意义(F=33.759,P=0.001).血小板(2～4×108/ml)eNOS mRNA表达在对照组、模型组、治疗组和非治疗组分别是1.02±0.28、0.41±0.27、1.00±0.77、0.40±0.29,治疗组较非治疗组明显增高(F=3.544,P=0.02). 结论 血小板源eNOS表达与动脉粥样硬化及斑块的形成呈负相关;普伐他汀对动脉粥样硬化及斑块的逆转作用可能与血小板源eNOS有关.     

NO在大鼠胰十二指肠移植中的作用

目的:探讨一氧化氮(NO)在大鼠胰十二指肠移植中缺血再灌注损伤和细胞凋亡中的作用.方法:168只大鼠,72只雄性作为供体,96只雌性通过腹腔注射四氧嘧啶诱导糖尿病作为受体,采用双套管法建立糖尿病大鼠胰十二指肠移植动物模型,随机分为假手术组(n=24)、对照组(对照组n=24)、L-Arg组(n=24)和L-NAME组(...     

Role of gastric mucosal blood flow in gastroprotective effect of novel xanthine derivative

The effect of 3-ethyl-1-(6-hydroxy-6-methylheptyl)-7-propylxanthine (A90 6119) on 40% ethanol-induced gastric lesions and gastric mucosal blood flow was investigated in rats. Gastric mucosal blood flow was measured by the hydrogen gas clearance technique and the test compounds and vehicle were administered intraduodenally. A90 6119 dose-dependently increased gastric mucosal blood flow and decreased gross and histologic gastric mucosal injury induced by 40% ethanol. Both the gastric mucosal blood flow and protective effects of A90 6119 were completely attenuated by pretreatment with indomethacin. The findings demonstrate that A90 6119 protects against ethanol-induced gastric injury, and this effect involves stimulation of endogenous prostaglandin synthesis and an increase in gastric mucosal blood flow.This work was supported by a grant from Hoechst Japan Ltd., Veterans Administration Research Funds, and the facilities and expertise of the Blood Flow Core of the Center for Ulcer Research and Education.     

内皮素，一氧化氮在内毒素血症大鼠胃粘膜损伤中的作用

目的：观察内皮素－1（ET－1）、一氧化氮（NO）在内毒素血症胃粘膜扣伤中的作用。方法：应用内毒素血症胃粘膜损伤模型分别观察血浆、胃粘膜中ET－1、NO含量变化,以及胃粘膜血流（GMBF）、胃粘膜损伤面积的变化。结果：内毒素血症时ET－1含量增加、NO含量减少,特异性内皮素受体ETAR阻滞剂（BQ123）、NO前体L－精氨酸（L－Arg）能减轻内毒素血症时胃粘膜损伤的程度。一氧化氮合酶阻滞剂N^G－硝基－L－精氨酸甲酯（L－NAME）加重了该模型胃粘膜的损伤。结论：内源性ET－1／NO失衡参与了内毒素血症时胃粘膜损伤病理过程。纠正内源性ET－1／NO失衡,通过改善了GMBF,减轻胃粘膜损伤。     

Age-dependent endothelial dysfunction is associated with failure to increase plasma nitrite in response to exercise

Age-dependent alterations of the vessel wall may predispose older individuals to increased cardiovascular pathology. Aging is associated with an impaired bioactivity of nitric oxide (NO). Plasma nitrite reflects NO-synthase activity under fasting conditions and is an important storage pool of NO. To test the hypothesis that aging is associated with an impaired capacity of the vasculature to increase plasma nitrite during exercise, 29 young and 28 old healthy individuals (25 ± 1 years and 58 ± 2 years; P < 0.001) without major cardiovascular risk factors were enrolled. Exercise stress was similar in both groups. Baseline nitrite did not differ (107 ± 8 vs. 82 ± 10 nmol/l, young vs. old; n.s.) although a trend toward higher nitrite levels in young individuals was seen. In young subjects, exercise increased plasma nitrite by 38 ± 7% (P < 0.001) compared to only 13 ± 8% (P = n.s.) in older subjects. L-NMMA blocked increases of nitrite. Endothelial function, as defined by flow–mediated-dilation (FMD) of the brachial artery via ultrasound, was impaired in older subjects (5.4 ± 0.4% vs. 6.7 ± 0.3%; P < 0.01). Multivariate analysis showed that age (P = 0.007), BMI (P = 0.010), and LDL (P = 0.021) were independent predictors of nitrite increase. The fact that aging is associated with an impaired capacity of the vasculature to adequately increase nitrite to physiological stimuli may contribute to attenuated maintenance and further deterioration of vascular homeostasis with aging.     

一氧化氮在雷贝拉唑对大鼠胃黏膜损伤保护中的作用

目的:探讨一氧化氮(NO)在雷贝拉唑对大鼠胃黏膜损伤保护中的作用．方法:在乙醇诱导大鼠胃黏膜损伤前,预先给予雷贝拉唑(20 mg/kg)灌胃,1-硝基-精氨酸甲酯(1-NAME,4 mg／kg)、1-精氨酸(250 mg／kg)及d-精氨酸(250 mg／kg)iv．采用激光多普勒血流计(LDF)测定胃黏膜血流量(GMBF),采用镉粒还原和比色法测定胃黏膜和血浆NO-2／NO-3含量,并观察胃黏膜损伤指数(UI)、溃疡坏死组织和中性粒细胞浸润严重程度的变化．结果:与模型损伤组比,雷贝拉唑组大鼠UI明显降低(5．5±0．5 vs 25．2±2.3,P<0．01),溃疡坏死组织和中性粒细胞浸润程度明显减轻(坏死物质 → ／≤ :1／9 vs 8／2,P<0．01;中性粒细胞 → ／≤ :3／7 vs 9／1,P<0．01)．预先用1-NAME处理后,雷贝拉唑保护胃黏膜损伤作用明显减弱;1-NAME抑制作用可被1-精氨酸拮抗,而不被d-精氨酸拮抗．向胃内灌注雷贝拉唑,可增加GMBF、胃黏膜和血浆NO-2／NO-3,1-NAME可逆转这种作用,但对雷贝拉唑抑制酸分泌作用无明显影响．结论:雷贝拉唑对大鼠胃黏膜损伤保护作用与NO有关,而与雷贝拉唑抑制酸分泌作用无关．     

伊贝沙坦对糖尿病大鼠一氧化氮系统及肾脏的影响

目的　研究伊贝沙坦对糖尿病大鼠一氧化氮 (NO)系统及肾脏的影响。　方法　随机将 4 0只Wistar大鼠分为 4组 ,每组 10只 ,分别为正常对照组、糖尿病组、伊贝沙坦组和开搏通组。病程 12周时处死大鼠 ,取血、尿和肾脏标本 ,测定尿量、体重、肾重 /体重比值、血糖、糖化血红蛋白(HbA1c) ;测定血清、尿液和肾组织的NO水平 ,通过免疫组化方法 ,检测肾脏组织诱导型一氧化氮合酶 (iNOS)蛋白的合成 ,并通过光镜和电镜观察肾脏的病理结构变化。　结果　治疗 12周后 ,糖尿病各组大鼠的尿量、肾重 /体重比值、血糖、HbA1c、血清、尿液和肾脏组织的NO水平、肾脏组织iNOS蛋白的合成、肾小球体积和肾小球基底膜厚度明显高于或大于正常组 ,体重明显低于正常组 (P <0 .0 1) ;伊贝沙坦组大鼠的血清、尿液和肾脏组织的NO水平、肾脏组织iNOS蛋白的合成、肾小球体积和肾小球基底膜厚度比糖尿病组明显减少 (P <0 .0 5 ) ;血清、尿液和肾组织NO水平与肾小球体积和肾小球基底膜厚度呈正相关。　结论　伊贝沙坦能延缓糖尿病大鼠肾脏功能损害的进展 ,其机制可能与伊贝沙坦不同程度地抑制糖尿病大鼠NO的产生有关。     

自发性高血压大鼠血清和心肌一氧化氮浓度的变化及L-精氨酸对其抑制作用

目的 :观察补充左旋精氨酸 4周后 12～ 13周龄自发性高血压大鼠 (SHR)血清和心肌组织一氧化氮(NO)浓度及血压的变化。方法 :通过腹腔注射补充NO合成前体———左旋精氨酸 (L Arg) 4周 ,硝酸还原酶法测定血清和心肌组织NO浓度 ;鼠尾压测量仪测量大鼠尾动脉的收缩压。结果 :治疗组SHR与对照组SHR相比心肌NO浓度降低 (P <0 .0 5 ) ,两组间血清NO浓度、血压差异无显著性意义 (P >0 .0 5 )。结论 :SHR 12～ 13周龄时体内NO呈代偿性地升高 ,通过腹腔注射慢性补充L Arg 4周使心肌组织NO浓度下降 ,但未能降低SHR已形成的高血压。     

Renal xanthine oxidoreductase activity during development of hypertension in spontaneously hypertensive rats

BACKGROUND: Hyperuricaemia and reactive oxygen species have recently been associated with essential hypertension. Xanthine oxidoreductase (XOR) produces urate and, in its oxidase isoform, reactive oxygen species also. Our previous studies indicated that hypertension-prone rat strains have greater renal XOR activity than their normotensive counterparts, and that dietary sodium modifies renal XOR activity. OBJECTIVE: To clarify whether renal XOR induction precedes or follows the development of hypertension. METHODS: Five-week-old spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were kept for 3-8 weeks on low sodium (0.3% salt w/w) or high sodium (6.0% salt w/w) intakes, with or without allopurinol, an inhibitor of XOR, to study the possible pathogenetic role of XOR in hypertension. Systolic blood pressure (SBP), renal XOR activity and mRNA expression were measured. RESULTS: Regardless of sodium intake, renal XOR activity increased twofold during growth in SHRs, but not in WKY rats. SBP increased from 122 +/- 4 to 241 +/- 13 mmHg in SHRs kept on the high-sodium diet and to 204 +/- 11 mmHg in those on the low-sodium diet. At the end of the experiment, renal XOR activity correlated with SBP in SHRs. Allopurinol prevented hypertension-induced left ventricular and renal hypertrophy in SHRs, but had negligible effect on blood pressure. CONCLUSION: Renal XOR induction in SHRs does not precede the development of hypertension, but progress concomitantly with an increase in SBP. The results indicate a role for locally synthesized XOR in the development of hypertension-associated end-organ damage, but no major role in the development of hypertension.     

Role of PGI2 in the formation and maintenance of hyperdynamic circulatory state of portal hypertensive rats

AIM: To investigate the role of prostacyclin (PGI2) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats. METHODS: Ninety male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) group by injection of CCI4, prehepatic portal hypertension (PHPH) group by partial stenosis of the portal vein and sham-operation control (SO) group. One week after the models were made, animals in each group were subdivided into 4 groups: saline controlled group (n = 23), Nω-nitro-L-arginine (L-NNA)group (n = 21) group, indomethacin (INDO) group (n = 22) and high-dose heparin group (n = 24). The rats were administrated 1mL of saline, L-NNA (3.3 mg/kg-d) and INDO (5 mg/kg·d) respectively through gastric tubes for one week/then heparin (200 IU/Kg/min) was given to rats by intravenous injection for an hour. Splanchnic and systemic hemodynamics were measured using radioactive microsphere techniques. The serum nitrate/nitrite(NO2-/NO3-) levels as a marker of production of NO were assessed by a colorimetric method, and concentration of 6-keto-PGF1α, a stable hydrolytic product of PGI2, was determined by radioimmunoassay. RESULTS: The concentrations of plasma 6-keto-PGFla (pg/mL) and serum NO2-/NO3- (μmol/L) in IHPH rats (1123.85±153.64, 73.34±4.31) and PHPH rats (891.88±83.11, 75.21±6.89) were significantly higher than those in SO rats (725.53±105.54, 58.79±8.47) (P<0.05). Compared with SO rats, total peripheral vascular resistance (TPR) and spanchnic vascular resistance (SVR) decreased but cardiac index (CI) and portal venous inflow (PVI) increased obviously in IHPH and PHPH rats (P<0.05). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGFla and serum NO2/7NO3-in IHPH and PHPH rats (P<0.05) .Meanwhile, CI, FPP and PVI lowered but MAP, TPR and SVR increased(P<0.05). After deduction of the action of NO, there was no significant correlation between plasma PGI2 level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of the action of PGI2, NO still correlated highly with the hemodynamic parameters, indicating that there was a close correlation between NO and the hemodynamic parameters. After administration of high-dose heparin, plasma 6-keto- concentrations in IHPH, PHPH and SO rats were significantly higher than those in rats administrated vehicle (P<0.05). On the contrary, levels of serum NO2-/NO3- in IHPH, PHPH and SO rats were significantly lower than those in rats administrated Vehicle (P<0.05). Compared with those rats administrated vehicle, the hemodynamic parameters of portal hypertensive rats, such as CI and PVI, declined significantly after administration of high-dose heparin (P<0.05), while TPR and SVR increased significantly (P<0.05). CONCLUSION: It is NO rather than PGI2 that is a mediator in the formation and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.     

大鼠组织一氧化氮含量变化及其调节在衰老过程中的作用

目的　揭示大鼠组织一氧化氮 ( NO)含量和一氧化氮合酶 ( NOS)活性变化与衰老的相关关系 ,并通过调节 NO合成 ,探讨 NO在衰老过程中的作用。　方法　对不同月龄大鼠采用铜离子活化镉还原法测定组织 NO含量 ,应用血红蛋白氧化法测定组织 NOS的活性 ,采用硫代巴比妥酸染色法测定组织丙二醛 ( MDA)含量。　结果　与青年组相比 ,老年组 ( 2 0～ 2 2月龄 )心脑肾组织 NO降低有显著性 ( P<0 .0 1 ) ,而中年组仅肾组织 NO含量降低有显著性 ( P<0 .0 5) ;老年组较中年组仅心脏组织 NO含量降低有显著性 ( P<0 .0 1 )。中年组心脑组织 NOS活性较青年组降低 ( P<0 .0 5) ;而老年组组织 NOS活性较中年组增高 ,仅脑组织 NOS增高有显著性 ( P<0 .0 5)。与老年对照组比较 ,β-雌二醇组心肝肾脑组织 NO含量明显增高 ( P<0 .0 1 ) ,而心脑肾组织 MDA下降有显著性 ( P<0 .0 1 ) ;L-硝基精氨酸甲酯组肝组织 NO降低有显著性 ( P<0 .0 5) ,而 MDA下降仅在脑组织有显著性 ( P<0 .0 5)。　结论　大鼠组织 NO含量与衰老之间存在一定的相关关系。     

维生素E对糖尿病大鼠肾脏的保护作用

目的探讨维生素E对糖尿病大鼠肾脏保护作用及其可能机制。方法实验动物分为正常对照组、链脲佐菌素诱导的糖尿病未治疗组、糖尿病给予维生素E（20mg.kg-1.d-1）治疗组,共观察8周。测定尿白蛋白排泄量(UAE),内生肌酐清除率（Ccr）、血浆及肾脏组织一氧化氮（NO）、一氧化氮合成酶（NOS）、内皮素（ET）和肾小球蛋白激酶C（PKC）。结果2周时糖尿病未治疗组Ccr［(6.47±1.51)ml·min-1·kg-1］、尿白蛋白排泄量［(15.60±1.64)μg/24h］、NO［(37.30±3.77)μmol/L］、NOS［(34.89±3.83)U/L］及肾小球细胞膜PKC［(86.85±11.37)pmol·min-1·mgprotein-1］明显高于对照组,ET低于对照组。8周时糖尿病大鼠肾小球细胞膜PKC［(84.18±12.14)pmol·min-1·mgprotein-1］仍明显高于对照组,但NO［(22.75±2.89)μmol/L］及NOS［(21.34±1.92)U/L］低于对照组,ET高于对照组。给予维生素E治疗组8周时,Ccr［(4.46±0.49)ml·min-1·kg-1］及尿白蛋白量［(16.31±1.12)μg/24h］显著低于未治疗组,8周时肾小球细胞膜PKC［(65.19±8.83)pmol·min-1·mgprotein-1］,2周时NO［(33.13±3.77)μmol/L］及NOS［(30.16±2.89)U/L］明显低于未治疗组,维生素E治疗组2周时与8周时的NO及NOS下降幅度明显小于未治疗组。结论维生素E通过抑制蛋白激酶C可以纠正糖尿病早期的肾脏高滤过、高灌注,并与抑制肾脏NO合成有关,抑制蛋白激酶C活性对糖尿病肾病防治尤为重要。