一氧化氮在大鼠肝硬变门静脉高压症形成中的作用及其对血液动力学 …

目的 探讨一氧化氮（ＮＯ）在肝硬变门静脉高压症（ＰＨＴ）形成过程中的作用。方法 采用比色法和鲎试验改良基质显色法,对大鼠肝硬变ＰＨＴ形成过程中,外周血ＮＯ、内毒素浓度和血液动力学的变化进行检测,观察了ＮＯ合成酶抑制剂Ｌ－ＮＭＭＡ对ＰＨＴ大鼠血液动力学的影响。 结果 （１）在大鼠肝硬变ＰＨＴ形成过程的早、中、晚三期,血浆ＮＯ和内毒素水平显著升高。（２）在肝硬变形成各期门静脉阻力（ＰＶＲ）和门静脉压力     

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.     

Overexpression of inducible nitric oxide synthase in gastric mucosa of rats with portal hypertension: correlation with gastric mucosal damage

BACKGROUND: An increased biosynthesis of nitric oxide (NO) has been implicated in the hyperdynamic circulation and development of collaterals of portal hypertension (PHT) because of its potent vasodilatory effects. NO is synthesized from L-arginine by three different isozymes of nitric oxide synthase (nNOS, iNOS and eNOS). Thus, the expression of inducible NOS (iNOS) might account for NO overproduction in PHT. However, in previous investigations, the role of iNOS in the pathogenesis of PHT gastropathy remained controversial. Our current study was in both molecular and protein levels to determine whether the expression of iNOS is responsible for PHT gastropathy. MATERIALS AND METHODS: PHT was induced experimentally by partial ligation of the portal vein. Fourteen days after partial ligation of the portal vein, the rats were randomly assigned to receive either vehicle or L-NAME (NOS inhibitor) at doses of 5 mg/kg/day, 10 mg/kg/day, or 25 mg/kg/day by gastric lavage twice a day for 1 week. Sham operated rats served as controls. Northern hybridization and in situ hybridization are used to compare the expression of gastric mucosa iNOS mRNA in the PHT rats and the controls. NO was measured by the Griess method after reduction of nitrate to nitrite with nitrate reductase. Immunohistochemical staining was carried out to detect the iNOS protein. In addition, the severity of gross gastric mucosal lesions was evaluated macroscopically by a gross ulcer index. RESULTS: The iNOS expression at both mRNA and protein was prominently increased in PHT rats, accompanied with the enhanced NO production. The gastric mucosa iNOS mRNA and serum NO levels were significantly decreased after L-NAME administration (P < 0.05). However, the markedly reduced gastric mucosal damage in PHT rats was observed only at high does of L-NAME (25 mg/kg/day) administration. CONCLUSION: PHT triggers overexpression of iNOS mRNA and proteins in rat gastric mucosa, but that this alone does not account for PHT gastropathy.     

一氧化氮在大白鼠肝硬变门静脉高压症中的作用

为探讨一氧化氮在肝硬变形成过程中的作用，我们通过观察一氧化氮合成酶在正常鼠和肝硬变、门静脉高压症大鼠肝脏的分布，同时测定了门静脉血亚硝酸盐／硝酸盐离子水平，并监测两组动物的血液动力学指标。结果发现：正常鼠肝脏的一氧化氮合成酶染色阴性，肝硬变鼠肝脏的再生假小叶内肝细胞的一氧化氮会成酶染色为强阳性；两组动物门静脉血的亚硝酸盐／硝酸盐离子的浓度分别为９．８±３．２ｕｍｏｌ／Ｌ，２６．７±６．８ｕｍｏｌ／Ｌ，差异有极显著性意义（Ｐ＜０．０１）；肝硬变大鼠的门静脉压力、门静脉血流量显著高于正常大鼠（Ｐ＜０．０５），而内脏血管阻力显著低于正常大鼠（Ｐ＜０．０５）。结果提示：一氧化氮在肝细胞的损伤及肝硬变门静脉高压的血液动力学改变中起重要作用。     

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.     

Responsiveness to inhaled NO in isolated-perfused lungs from endotoxin-challenged rats is dependent on endogenous nitrite/nitrate synthesis

BACKGROUND AND OBJECTIVES: In isolated-perfused lungs of lipopolysaccharide (LPS)-challenged rats, vasodilatation to inhaled nitric oxide (NO) is impaired. Inhibition of nitric oxide synthase 2 (NOS2) by aminoguanidine (AG) prevented hyporesponsiveness to inhaled NO. Here, we investigated whether NOS2-mediated nitrite/nitrate synthesis modulates responsiveness to inhaled NO. METHODS: Sprague-Dawley rats received intraperitoneally 0.5 mg kg(-1) LPS. Four hours later, LPS-treated rats received 3, 10 or 30 mg kg(-1) AG or 0.01, 0.1 or 1 mg kg(-1) S-methylisothiourea (SMT) by intraperitoneal injection. Sixteen to eighteen hours later, lungs were isolated and perfused, and pulmonary artery pressure (PAP) was elevated by 6-8 mmHg using the thromboxane analogue U46619. The decrease of PAP in response to inhaled NO and nitrate/nitrite levels in serum and perfusate was measured. RESULTS: In rats treated with LPS alone or 0.01 or 0.1 mg kg(-1) SMT, 40 ppm NO decreased PAP less than in rats treated with AG and 1 mg kg(-1) SMT (-1.8 mmHg (95% confidence interval: -1.5 to -2.1) vs. -6.0 mmHg (-5.7 to -6.3), P < 0.01). Improved NO responsiveness was associated with lower serum and perfusate nitrite/nitrate levels than in rats with hyporesponsiveness to inhaled NO (102 micromol (82-122) vs. 282 micromol (261-303) and 8.1 micromol (6.9-9.3) vs. 19.8 micromol (17.2-22.4), respectively, P < 0.01). CONCLUSIONS: These observations demonstrate that in isolated-perfused lungs of LPS-treated rats, NOS2 inhibition improved responsiveness to inhaled NO. Here, responsiveness to inhaled NO is dependent on the ability of NOS2 inhibitors to reduce nitrite and nitrate levels in serum and released in the lung.     

Local arginine supplementation results in sustained wound nitric oxide production and reductions in vascular endothelial growth factor expression and granulation tissue formation

OBJECTIVE: The goal of this work was to test the functional role of L-arginine in promotion of nitric oxide (NO) production and the vigorous granulation tissue formation characteristic of this wound model. BACKGROUND: Therapeutic use of supplemental arginine has been proposed as a safe and efficacious method to produce NO from nitric oxide synthase (NOS) and to produce proline and polyamines from arginase to improve wound healing. Although NO appears to be necessary to promote wound healing, the preferential metabolism of arginine to NO via NOS 2 may be detrimental if maintained beyond the initial days of healing. METHODS: A ventral hernia, surgically created in the abdominal wall of 12 swine, was repaired with silicone sheeting and skin closure. Osmotic infusion pumps, inserted in remote subcutaneous pockets, continuously delivered saline (n = 6) or L-arginine (n = 6) into the wound environment. Granulation tissue thickness was determined by ultrasonography. Fluid was aspirated serially from the wound compartment for measurements of nitrite/nitrate (NOx), vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), and amino acid concentrations. On day 14, the animals were sacrificed and the abdominal wall was harvested for immunohistochemical and molecular analysis. RESULTS: In animals receiving saline, a nearly linear four-fold increase in granulation tissue thickness was measured during the 14-day interval. In contrast, quantitative ultrasound analysis detected significant reductions in L-arginine infused granulation tissue thickness compared with controls between days 4 and 14 (P < 0.05). Wound vessel count and luminal vascular surface area estimates derived from image analysis of histological sections were two- to three-fold lower in the L-arginine animals compared with controls (P < 0.05). Significant and sustained increases in wound fluid NOx levels were noted in L-arginine animals compared to saline controls (230 microM versus 75 microM at day 14, P < 0.05). Conversely, late VEGF levels (days 11 to 14) were reduced in the L-arginine animals compared to controls (7500 pg/ml versus 10,000 pg/ml at day 11, P < 0.05; 7250 pg/ml versus 11,101 pg/ml at day 14, P < 0.05). Arginine concentrations remained two- to four-fold greater in L-arginine treated animals compared with controls over the entire time course (P < 0.05). There were no significant differences in concentrations of ornithine, citrulline, or proline noted between groups over the 14-day period. Finally, TGF-beta1 levels were unaffected by L-arginine treatment. CONCLUSION: Although NO appears to be necessary for granulation tissue formation, early supplemental arginine may disturb the reciprocal regulation of NOS 2 and arginase, leading to the preferential metabolism of arginine to excess NO rather than ornithine, with consequent reductions in angiogenesis and granulation tissue formation.     

一氧化氮在门静脉高压症发病中的作用

目的　探讨一氧化氮在门静脉高压症发病中的作用。　方法　 75例门静脉高压症患者 ,术中胃网膜静脉插管测定门静脉压力 ,检测外周动静脉和门静脉血中内毒素和NO2 -/NO3-的含量。　结果　 ( 1)门静脉高压症患者的血中内毒素和NO2 -/NO3-的水平 [( 0 2 4 9± 0 112 )Eu/ml和( 5 5 9± 2 6 2 ) μmol/L]均显著高于对照组 ,且门静脉血中水平最高。 ( 2 )门静脉高压症患者门静脉压力[( 3 5 5± 4 4 )cmH2 O]与门静脉血NO2 -/NO3-的水平呈显著正相关 (n =2 5 ,r =0 5 5 ,P <0 0 1) ,二者在术后的变化量也呈正相关 (r =0 5 7,P <0 0 5 )。 ( 3 )门静脉高压症患者白蛋白水平与NO2 -/NO3-呈负相关 (n =75 ,r=- 0 3 5 ,P <0 0 1) ,且有腹水组的NO2 -/NO3-水平 [( 72 4± 2 0 3 ) μmol/L]较无腹水组 [( 5 0 3± 2 1 0 ) μmol/L]为高。　 结论　门静脉高压症患者血中内毒素和NO的水平升高 ,后者可能参与了门静脉压力的异常升高且与肝功能损害有关。     

Inducible nitric oxide production is an adaptation to cardiopulmonary bypass-induced inflammatory response

BACKGROUND: Cardiopulmonary bypass (CPB) increases nitric oxide (NO) production by the activation of NO synthases (NOS). However, the role of NO from inducible NOS (iNOS) in CPB-induced inflammatory response remains unclear. We examined the effect of a selective iNOS inhibitor, aminoguanidine, on CPB-induced inflammatory response in a rat-CPB model. METHODS: Adult Sprague-Dawley rats underwent 60 minutes of CPB (100 mL x kg(-1) x min(-1), 34 degrees C). Group A (n = 10) received 100 mg/kg of aminoguanidine intraperitoneally 30 minutes before the initiation of CPB, and group B (n = 10) served as controls. RESULTS: There were significant time-dependent changes in plasma interleukin (IL)-6, IL-8, nitrate + nitrite, the percentage ratio of nitrotyrosine to tyrosine (%NO2-Tyr, an indicator of peroxynitrite formation), and respiratory index (RI). Three hours after CPB termination, IL-6, IL-8, and RI were significantly higher in group A (IL-6, 397.5+/-80.6 pg/mL; IL-8, 26.99+/-6.57 ng/mL; RI, 1.87+/-0.31) than in group B (IL-6, 316.5+/-73.9 pg/mL, p <0.05; IL-8, 17.21+/-3.12 ng/mL, p < 0.01; RI, 1.57+/-0.24, p < 0.05) although nitrate + nitrite (31.8+/-4.1 micromol/L) and %NO2-Tyr (1.15%+/-0.20%) were significantly lower in group A than in group B (nitrate + nitrite, 50.2+/-5.0 micromol/L, p < 0.01; %NO2-Tyr, 1.46%+/-0.21%, p < 0.01). Western immunoblot analysis from lung tissue of group A identified marked iNOS inhibition without inhibiting endothelial-constitutive NOS, and neutrophil accumulation in the lung specimens was significantly greater in group A (6.5+/-0.7/alveoli) than in group B (4.4+/-0.4/alveoli, p < 0.01). CONCLUSIONS: These results suggest that NO production from iNOS may be an adaptive response for attenuating the CPB-induced inflammatory response.     

重组杀菌／通透性增加蛋白对内毒素休克中肝脏一氧化氮合酶的 …

目的：探讨重组杀菌／通透性增加蛋白（ｒＢＰＩ２１）对内毒素休克中肝组织一氧化氮合酶（ＮＯＳ）的影响及其意义。方法 大鼠腹腔注射大肠杆菌内毒素（１５．０ｍｇ／ｋｇ）复制内毒素休克模型，动物随机分成正常对照组、内毒素休克组和ｒＢＰＩ２１治疗组。检测肝组织ＮＯＳ活性、三磷酸鸟苷环水解酶Ｉ（ＧＴＰ－ＣＨＩ）活性及生物喋呤含量，同时还观察肝脏微循环血流灌注量的改变。结果 内毒素攻击后肝组织诱生型ＮＯＳ（ｉＮ     

一氧化氮、一氧化氮合酶与伴精索静脉曲张不育患者精液参数的关系

目的:探讨一氧化氮(NO)、一氧化氮合酶(NOS)与伴精索静脉曲张(VC)不育患者精液参数之间的关系。方法:根据体格检查和彩色多普勒超声检查选择伴VC的不育患者(组1,n=53),其中临床型和亚临床型分别为21例和32例;同时选择非VC少弱精子症患者(组2,n=29)和正常生育者(组3,n=28)作对照组。采用硝酸还原法分别测定外周血和精浆中NO含量和NOS活性。用计算机辅助精液分析仪测定VC组患者精子密度、活动精子(a+b级精子)和快速前向运动精子百分率。结果:①组1外周血清NO含量和NOS活性与组2及组3相比差异无显著性(P>0.05),但精浆中NO含量和NOS活性组1明显高于其他两组,差异有显著性(P<0.01和P<0.05)。②组1中,随着曲张的精索静脉内径的增加,外周血清和精浆中NO含量和NOS活性均有所上升,但只有精浆中临床型和亚临床型之间相比差异有显著性(P<0.05)。③组1中,随着精子密度和精子活力的下降,外周血清和精浆中NO含量和NOS活性均有上升趋势,且精子密度≥20×106/ml和≤10×106/ml之间,精子活力≥50%和≤25%之间差异有显著性(P均<0.05)。结论:在VC诊断中精浆中NO含量和NOS活性测定较外周血清中更有意义。早期测定精浆NO含量和NOS活性对VC的诊断和治疗具有重要的临床价值。     

Evaluation of Low-dose Endotoxin Administration during Pregnancy as a Model of Preeclampsia

Background: Recent evidence implicates nitric oxide ( [middle dot] NO) in the pathogenesis of preeclampsia. The authors tested the hypothesis that administration of low-dose endotoxin to pregnant rats mimics the signs of preeclampsia in humans and that [middle dot] NO and [middle dot] NO-derived species play a role in that animal model.

Methods: Endotoxin was infused at doses of 1, 2 and 10 [mu]g/kg over 1 h to rats on day 14 of pregnancy. Mean arterial pressure, urinary protein, urinary and plasma nitrite plus nitrate (NO2- + NO3-) concentrations, and platelet count were measured before and after the endotoxin infusion. In another group of pregnant rats, the nitric oxide synthase inhibitor l-nitroarginine methyl ester (l-NAME) was administered in drinking water at a dose of 3 mg [middle dot] kg-1 [middle dot] d-1 starting on day 7 of pregnancy. Endotoxin was then infused at 10 [mu]g/kg on day 14 of pregnancy. Kidneys and uteroplacental units were examined histologically and analyzed immunohistochemically for 3-nitrotyrosine.

Results: Endotoxin administration at doses of 2 and 10 [mu]g/kg caused proteinuria and thrombocytopenia in pregnant rats, but did not result in hypertension. Urinary NO2- + NO3- concentration, reflective of tissue [middle dot] NO production rates, was significantly elevated in pregnant rats that received endotoxin at 10 [mu]g/kg. Ingestion of l-NAME caused hypertension. Tissues from pregnant rats treated with l-NAME, endotoxin at 10 [mu]g/kg, and a combination of l-NAME and endotoxin had increased 3-nitrotyrosine immunoreactivity.     

The effects of erdosteine on lung injury induced by the ischemia-reperfusion of the hind-limbs in rats

BACKGROUND: [corrected] The goal of this experimental study was to investigate whether erdosteine has a protective effect against lung injury as a remote organ after hind-limb ischemia-reperfusion (I/R). MATERIALS AND METHODS: The rats were divided into three groups: control, I/R, and I/R + erdosteine. After the experimental procedure, nitric oxide (NO) levels, myeloperoxidase (MPO), adenosine deaminase (ADA), and the activities of xanthine oxidase (XO) were determined on the lung tissue. The levels of NO and activities of MPO were also measured on the bronchial alveolar lavage (BAL). In addition, the lung tissue was examined by histopathology. RESULTS: The lung tissue ADA and XO activities were increased in the I/R group compared with the control group (P < 0.05). In the I/R group, the levels of NO were higher than the control group (P < 0.05), whereas the erdosteine treatment did not alter the NO levels (P < 0.05). The MPO activities increased after I/R in the I/R group compared to both control and I/R + erdosteine group (P < 0.05). The activity of MPO increased in the IR group in comparison with the control group in BAL (P < 0.05). The activity of MPO in the I/R + erdosteine group was significantly lower than the I/R group in BAL (P < 0.05). NO levels increased in all I/R groups compared to control group in BAL (P < 0.05). However, treatment of erdosteine significantly decreased NO levels compared to I/R group (P < 0.05). The animals of the I/R group had total destruction of normal alveolar structure with the intense presence of infiltrating neutrophils and mononuclear phagocytes in histopathological examination. The rat lung exhibited mild degrees of destruction in the erdosteine group. CONCLUSIONS: As a result, erdosteine may be a protective effect for lung injury, decreasing oxidative stress and neutrophil accumulation after hind-limb I/R in rats.     

慢性肾功能衰竭性勃起功能障碍大鼠阴茎海绵体有效成分的测定

目的:探讨慢性肾功能衰竭(CRF)性勃起功能障碍(ED)的发病机制。方法:应用SD雄性大鼠分两期行5/6肾脏切除术,建立CRF动物模型。将假手术组(NCRF组,n=30)、CRF模型大鼠(CRF组,n=45)分别随机均分为Ⅰ(2周)、Ⅱ(4周)、Ⅲ(6周)3组,并分别于2、4、6周注射阿朴吗啡(APO,80μg/kg)后观察大鼠阴茎勃起情况,筛选CRF性ED模型大鼠;测定阴茎海绵体组织一氧化氮合酶(NOS)的活性,及其组织的M asson染色图像分析。结果:CRF性ED大鼠阴茎海绵体组织NOS活性及平滑肌面积显著降低(P<0.01或P<0.05),胶原纤维略有增加,且上述变化与CRF病程密切相关。海绵窦血管腔无明显变化。结论:CRF严重影响阴茎勃起功能,阴茎海绵体组织NOS活性降低及阴茎海绵体平滑肌面积的减少可能是其重要的发病机制。     

Epidural Anesthesia Retards Intestinal Acidosis and Reduces Portal Vein Endotoxin Concentrations during Progressive Hypoxia in Rabbits

Background: Because it is postulated that gut is important via bacterial translocation in the development of the systemic inflammatory response and multiple organ dysfunction, the preservation of gut integrity is a therapeutic goal for physicians who care for critically ill patients. The aim of the current study was to evaluate whether epidural anesthesia prevented gut injury and subsequent translocation of endotoxin during acute progressive hypoxia in rabbits.

Methods: After the placement of an epidural catheter, 18 male rabbits, anesthetized with buprenorphine-midazolam, were allocated randomly to two groups: 0.5% lidocaine (group E) and saline (group C) groups. The solutions (0.4 ml/kg) were injected epidurally, followed by continuous infusion (0.1 ml[middle dot]kg-1[middle dot]h-1) during the study period. Portal blood flow, portal endotoxin concentrations, and intramucosal pH (pHi) of the ileum were measured at baseline and during two stages of progressive hypoxia (fraction of inspired oxygen [Fio2] = 0.15 and 0.10).

Results: In both study groups, the portal blood flow was preserved to a similar extent during acute hypoxia. However, pHi was reduced to a lesser extent in group E (7.33 +/- 0.12 versus 7.22 +/- 0.12 at an Fio2 of 0.15 and 7.13 +/- 0.15 versus 7.03 +/- 0.12 at an Fio2 of 0.10; mean +/- SD, P < 0.01), concurrently with lower portal endotoxin concentrations (P < 0.05) compared with group C.     

Flow induces dilatation in the femoral artery of uraemic rats but constriction in control rats.

BACKGROUND: Pressure and flow are recognized as important modulators of vascular tone. In mildly uraemic rats, myogenic tone is increased in the femoral artery in the absence of hypertension compared with healthy control rats, but the effect of flow in the same experimental model remains unknown. SUBJECTS AND METHODS: Twelve male Wistar rats were rendered uraemic (U) by 5/6th nephrectomy or were concurrently sham operated as controls (C). After 8 weeks, isolated femoral arteries were mounted on a flow myograph, pressurized at 80 mmHg, and constricted by 40-50% of the lumen internal diameter (i.d.) by L-phenylephrine (1-10 micromol/l). Flow was initiated (0-207 microl/min) in six steps every 5 min and changes in i.d. recorded. N-nitro-L-arginine methyl ester hydrochloride (L-NAME) (0.1 mmol/l) and 1H-[1,2,4] oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (1 micromol/l) were applied extraluminally and the flow protocol repeated. RESULTS: The baseline pre-constricted at 80 mmHg i.d. was significantly smaller in the U (U 255+/-21 microm vs C 365+/-36 microm, P<0.03). At all steps, flow elicited a dilatation in the U and a constriction in the C (U+ 24+/-8% vs C-17+/-5%, P<0.01). When L-NAME and ODQ were applied, a significant basal reduction in i.d. was observed in the C only (C 365+/-36 microm vs C+ L-NAME & ODQ 182+/-18 microm, P<0.01; U 255+/- 21 microm vs U+L-NAME & ODQ 240+/-11 microm, P=n.s.). Furthermore, in the U there was no significant blunting to dilatation during flow (+9+/-4%). CONCLUSIONS: Flow elicited a constriction in controls, but a marked dilatation in uraemic roots which was not entirely nitric oxide dependent. These results suggest that other mediators such as prostacyclin or endothelium-dependent hyperpolarizing factor, or changes in the vascular smooth muscle may contribute to flow-induced dilatation in mild experimental uraemia.     

Enteral administration of high-fat nutrition before and directly after hemorrhagic shock reduces endotoxemia and bacterial translocation

OBJECTIVE: To determine whether potential enhancement of endotoxin neutralization via high-fat enteral nutrition affects endotoxemia and bacterial translocation after hemorrhage. SUMMARY BACKGROUND DATA: Endotoxin and bacterial translocation due to gut barrier failure are important initiating events in the pathogenesis of sepsis after hemorrhage. Systemic inhibition of endotoxin activity attenuates bacterial translocation and distant organ damage. Triacylglycerol-rich lipoproteins constitute a physiological means of binding and neutralizing endotoxin effectively. We hypothesized that enhancement of triacylglycerol-rich lipoproteins via high-fat enteral nutrition would reduce endotoxemia and prevent bacterial translocation. METHODS: A rat model of nonlethal hemorrhagic shock was used. Hemorrhagic shock (HS) rats were divided into 3 groups: rats starved overnight (HS-S); rats fed with a low-fat enteral diet (HS-LF), and rats receiving a high-fat enteral diet (HS-HF). RESULTS: Circulating triacylglycerol and apolipoprotein B, reflecting the amount of triacylglycerol-rich lipoproteins, were elevated in HS-HF rats compared with both HS-S rats (P 相似文献   

Involvement of endothelial nitric oxide synthase in the impaired endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbit

The present study was designed to evaluate whether functional impairment and/or protein expression of constitutive nitric oxide synthase (cNOS; endothelial NOS [eNOS] and neuronal NOS[nNOS]) was involved in impairment of endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbits. New Zealand White rabbits were randomly divided into control and experimental groups. The control group (n=20) received a regular diet, while the two experimental groups (n=20 for each) were fed a 2% cholesterol diet for 4 and 8 weeks, respectively. We conducted isometric tension studies with endothelium-dependent and endothelium-independent vasodilators with or without preincubation with L-arginine and nonadrenergic, noncholinergic (NANC)-selective electrical field stimulation on isolated strips of corpus cavernosum. Expression of cNOS (eNOS and nNOS) protein was assessed by Western blot analysis. cNOS activities in both cytosolic and particulate fractions were measured by determining the conversion of L-[U-14C] arginine to L-[U-14C] citrulline. Blood levels of cholesterol were significantly higher (P < 0.01) in the experimental groups than in the control group. The relaxation responses to endothelium-dependent agents (acetylcholine and adenosine 5'-diphosphate [ADP]) were significantly reduced (P < 0.05) in both experimental groups, regardless of their incubation with L-arginine, compared with the control group. However, no differences were found among the three groups in the relaxation response to endothelium-independent agents (papaverine and nitroprusside) and to NANC-selective electrical field stimulation. There was no difference in immunoreactive nNOS from cytosolic and particulate fractions between the cavernous tissues of the control and experimental groups. nNOS protein levels in the particulate fractions were markedly lower than in the cytosolic fractions. The particulate cNOS activity was significantly decreased (P < 0.05) in the experimental groups compared with the control group, while the cytosolic cNOS activity in the experimental groups was not different from that found in the control group. Therefore, it is concluded that functional impairment of eNOS, rather than of nNOS, may lead to impairment of cavernous smooth muscle relaxation in response to endothelium-mediated stimuli in hypercholesterolemic rabbits.     

组织细胞间粘附分子-1在阻塞性黄疸小肠粘膜损伤中的作用及丹参防治机制的研究

目的：研究组织细胞间粘附分子－1（ICAM－1）在阻塞性黄疸（阻黄）小肠粘膜损伤中的作用及丹参防治小肠粘膜损伤机制。方法：SD大鼠48只分为4组：假手术对照组（SO＋NS）、阻黄组（BDL＋NS）、治疗对照组（SO＋SM）及丹参治疗组（BDL＋SM），每组术后再随机分设7、14d两个时相点。在不同时相点检测小肠组织髓过氧化物酶活性（MPO）、ICAM－1、二胺氧化酶（DAO）、血浆内毒素水平变化，并与丹参治疗组进行比较。结果：BDL＋NS组7、14d时小肠DAO的活性降低，MPO活性增高P＜0．05），门表脉血浆内毒素增加，ICAM－1主要表达在小肠粘膜上皮组织，且表达逐渐增强（P＜0．05）；BDL＋SM组7、14d时小肠组织DAO活性显著升高，门静脉血浆内毒素降低，ICAM－1表达受到抑制（P＜0．05），MPO改变不明显。结论：阻黄引起小肠上皮细胞上的ICAM－1表达上调，参与了中性粒细胞（PMN）介导的小肠粘膜损伤；丹参是通过抑制ICAM－1的表达而减轻小肠粘膜的损伤。     

肝硬变大鼠肝脏缺血再灌注损伤

为比较硬化肝与正常肝在缺血再灌注损伤时的差异和意义。作者采用四氯化碳复制大鼠肝硬变模型,通过大鼠肝脏缺血再灌注损伤模型,检查不同时限大鼠门静脉血内毒素、肝静脉血一氧化氮。结果显示：肝硬变大鼠再灌注时门静脉内毒素水平更高;肝脏ＮＯ合成释放显著增加。作者认为肝硬变时对缺血再灌注损伤反应与正常大鼠不同,可能是肝硬变时对缺血再灌注损伤更敏感,更易发生肝功能衰竭的重要原因。