L-精氨酸对围手术期胃癌病人炎性反应和免疫功能的影响

目的:研究L-精氨酸(L-Arg)对围手术期胃癌病人炎性反应和免疫功能的影响. 方法:将围手术期胃癌病人随机分为研究组和对照组,研究组(n=33)行营养支持加L-Arg治疗,L-Arg 0.4g/(kg·d)通过静脉给予;对照组(n=30)行营养支持治疗加等量的等渗盐水.能量供给为125.4 kJ/(kg·d),氮量为0.2g/(kg·d),治疗10d.观察胃癌病人术前3d、术后第3和第7天血清C-反应蛋白(CRP)、白细胞介素-2(IL-2)、IL-6、IL-10、肿瘤坏死因子-α(TNF-α)、T淋巴细胞亚群CD4+、CD8+水平和CD4 +/CD8+比值的变化. 结果:术后第7天,研究组病人血IL-2、TNF-α水平和CD4+/CD8+比值均明显高于对照组和术前3d,而血液CRP和IL-10水平明显低于对照组和术前3d.术后第7天,CRP水平明显低于术后第3天. 结论:L-Arg可影响胃癌病人的炎性反应水平,下调具有促进肿瘤生长能力的炎性因子水平,上调胃癌病人细胞免疫应答.     

Effect of L-Arginine Treatment in Pregnant Rats with Adriamycin Nephropathy

Objective: The influence of pregnancy (P) on the evolution of primary renal disease is still controversial. In rats with early adriamycin nephropathy (ADR), pregnancy enhanced mean arterial pressure (MAP) and urine protein excretion (UP). It has been suggested that the development of hypertension in pregnancy may be related to a decreased synthesis of vasodilatory substance(s) by endothelial cells. In the present study, the effect of L-arginine, a precursor of the endothelium-derived relaxing factor nitric oxide (NO), was evaluated.

Methods: Four groups of rats were studied (n = 10 each): 1—normal pregnancy (NP); 2-normal pregnancy treated with L-arginine (NP + LA); 3-ADR pregnant rats (ADRP); and 4-ADR pregnant rats treated with L-arginine (ADRP-1-LA). L-arginine, 2 g/1, was added to the drinking water from midpregnancy.

Results: In ADRP rats, MAP increased to 135 ± 4.1 mm Hg, significantly above the values of 91 ± 1.2 mm Hg found in NP rats, P <. 01. Treatment with L-arginine did not influence MAP in NP + LA rats, whereas in ADRP+LA animals, MAP decreased to 89 ± 5 mm Hg, P <. 01 vs. ADRP. In ADRP rats, UP increased from 11 ± 4 mg/d before P to 315 ± 55 mg/d at end P. By contrast, in ADRP + LA rats, UP increased only to 98 ± 23 mg/d, P <. 01 vs. ADRP rats. Inulin clearance was significantly greater in ADRP + LA than in ADRP rats, 2.37 ±. 21 vs. 1.45 ±. 01 ml/min, respectively, P <. 01.

Conclusions: These preliminary results suggested that in rats with incipient adriamycin nephropathy, the endogenous synthesis of NO might be inadequately low during pregnancy, leading to the development of hypertension and enhancement of urine protein excretion.     

L-硝基精氨酸与L-精氨酸干预对大鼠创伤性面瘫恢复的影响

 目的 研究组成型一氧化氮合酶抑制剂L-硝基精氨酸和一氧化氮前体L-精氨酸对大鼠创伤性面瘫恢复的影响.方法 通过大鼠面瘫前后腹膜内小剂量给予L-硝基精氨酸或L-精氨酸,在伤后各个时间点上观察面瘫的恢复.结果 L-硝基精氨酸慢性给药可显著延缓创伤性面瘫的恢复,而小剂量L-精氨酸慢性给药则可显著促进创伤性面瘫的恢复.结论 内源性NO介质在创伤性面瘫模型中具有显著的促面瘫恢复作用.     

左旋精氨酸对不对称二甲基精氨酸与一氧化氮水平的影响

目的 观察先天性心脏病合并中、重度肺动脉高压(PAH)行心内直视修补术患者静滴左旋精氨酸(L-Arg)对不对称二甲基精氨酸(ADMA)和一氧化氮(NO)水平的影响.方法 20例入院时肺动脉收缩压(PASP)＞50 mm Hg拟在心肺转流(CPB)下行心内修补术患者,随机分为L-Arg治疗组(Ⅰ组)和对照组(Ⅱ组),每组10例.Ⅰ组术前加用L-Arg静滴;Ⅱ组术前接受常规治疗.所有患者在治疗前(T1)、麻醉诱导前(T2)、停CPB时(T3)、CPB结束后12 h(T4)、24 h(T5)及72 h(T5)各采集桡动脉血,测定ADMA和NO的浓度.治疗前、术前、术后第1天及第3天各测一次PASP.结果 Ⅰ组和Ⅱ组T1时NO、ADMA及PASP差异无统计学意义.与T1时比较,Ⅰ组T2、T4～T6时NO浓度升高、T2～T6时ADMA浓度降低(P＜0.05);Ⅱ组T3～T6时NO浓度降低、T4～T6时Ⅰ组ADMA浓度明显升高(P＜0.05).T2、T4～T6时Ⅰ组NO浓度高于Ⅱ组、ADMA浓度低于Ⅱ组(P＜0.05);Ⅰ组PASP术前、术后第1天、第3天均低于Ⅱ组(P＜0.05).结论 CPB可致ADMA浓度增高、NO浓度降低.静注L-Arg可提高NO的浓度,降低ADMA浓度,而且对降低PAH患者行心内修补术后肺动脉压力有积极意义.     

左旋精氨酸通过活化树突状细胞增强约氏疟原虫感染DBA/2小鼠的Th1应答效应

目的探讨左旋精氨酸(L-Arginine,L-Arg)对致死型约氏疟原虫(Plasmodium yoelii 17XL,P.y17XL)感染DBA/2小鼠Th1免疫应答的调节效应。方法 DBA/2小鼠随机分为两组,对照组和L-Arg组,每组20只,分别给予DBA/2小鼠生理盐水和L-Arg(1.5g/kg)连续灌胃预处理7d后,每鼠经腹腔感染1×10~6个P.y17XL寄生的红细胞(pRBC)。统计两组小鼠红细胞感染率和小鼠存活率。感染后第0、3和5天每组分别处死4只小鼠,取脾组织制备脾细胞悬液,流式细胞术检测CD4~+CD69~+T细胞、F4/80~+CD36~+巨噬细胞、髓样树突状细胞mDCs(CD11c~+CD11b~+)、浆样树突状细胞pDCs(CD11c~+B220~+)数量,ELISA法检测脾细胞培养上清中γ干扰素(IFN-γ)的分泌水平,Griess反应检测脾细胞培养上清中一氧化氮(NO)含量。结果与对照组(45%)比较,L-Arg组小鼠的最高红细胞感染率降到20%,自愈时间从22d缩短到20d。感染后第3天,L-Arg组小鼠CD4~+CD69~+T细胞数量[(11.27±0.97)%]、IFN...     

Effects of Intragastric L-Arginine Administration on Proximal Stomach Tone Under Basal Conditions and After an Intragastric Diet

Nitric oxide (NO) plays an important role as a nonadrenergic, noncholinergic inhibitory neurotransmitter in the GI tract. Our study aims were to investigate the effect of a single intragastric L-arginine (L-Arg) administration, as a source of NO, on proximal stomach tone in basal and postintragastric administration of a polymeric diet in humans and to evaluate concomitantly the effect on antral area as an indirect assessment of gastric emptying. Eight healthy volunteers were studied in a randomized double-blind crossover study after, respectively, 15 g L-Arg, 30 g L-Arg, or placebo administered in the stomach through a gastric tube. The drug administration was followed by a polymeric diet infusion (500 ml/500 kcal) at a rate of 250 ml/hr. Gastric tone variations were recorded with an electronic barostat, gastric emptying was concomitantly estimated by repeated ultrasound measurements of antral area, and symptoms were recorded throughout the experiment. L-Arg administration was associated with significantly higher increases in barostat bag volumes at both dosages, 30 g (117±16 ml) and 15 g (67±15 ml), compared to placebo (46±11 ml; P < 0.05). In response to the polymeric diet the 30-g L-Arg challenge was associated with a smaller increase in intrabag volume, whereas postinfusion final volumes did not differ in the three treatment conditions. Antral areas were not different at any time of measurement among the three challenges. Bloating and diarrhea were observed after 30-g L-Arg administration in five subjects of eight. Short-term L-Arg administration was able to induce proximal stomach relaxation that allowed a secondary response to enteral feeding only at the 15-g dosage. This 15-g dosage was as well tolerated as the placebo and was associated with no significant changes in gastric emptying patterns.     

Influence of intracerebral administration of NO agents in dorsal hippocampus (CA1) on cannabinoid state-dependent memory in the step-down passive avoidance test

In the present study, the effects of nitric oxide agents on WIN55, 212-2 induced state-dependent memory of passive avoidance task were examined in mice. One-trial step-down paradigm was used for the assessment of memory retention in adult male NMRI mice. Post-training intra-CA1 administration of CB1 and CB2 receptor agonists, WIN55, 212-2 (0.25, 0.5 and 1 µg/mouse), dose-dependently decreased memory retrieval. The memory impairment induced by post-training administration of WIN55, 212-2 (1 µg/mouse) was restored by pre-test administration of the same dose of the drug (1 μg/mouse, intra-CA1), showing the WIN55, 212-2 state-dependent memory. Single intra-CA1 administration of l-arginine (0.3, 1 and 3 µg/mouse) or L-NAME (0.3, 1 and 3 µg/mouse), 5 min pre-test could not alter memory retrieval. On the other hand, in the animals in which retrieval was impaired due to post-training administration of WIN55, 212-2 (1 µg/mouse), pre-test intra-CA1 administration of l-arginine (1 and 3 µg/mouse), but not L-NAME (0.3, 1 and 3 µg/mouse) 24 h after training restored memory retrieval. Also, in the animals which received both post-training (1 µg/mouse) and pre-test injections of WIN55, 212-2 (1 µg/mouse), the injection of L-NAME (3 µg/mouse, intra-CA1), 2 min before pre-test administration decreased retrieval. Furthermore, in the animals under the influence of post-training administration of WIN55, 212-2 (1 µg/mouse), pre-test co-administration of non-effective doses of WIN55, 212-2 (0.25 µg/mouse) and l-arginine (0.3 and 1 µg/mouse), increased the restoration of memory by pre-test WIN55, 212-2. These findings may demonstrate the involvement of NO in state-dependent memory induced by intra-CA1 administration of WIN55, 212-2.     

L-arginine attenuates blood pressure and reverses the suppression of angiogenic risk factors in a rat model of preeclampsia

This study investigated the effect of L-arginine on blood pressure, angiogenic factors and liver enzymes in pregnant rats administered L-NAME. Thirty-six female Sprague-Dawley rats weighing between 150–170?g were divided into 4 groups of the control (normal saline), L-NAME (50?mg/kg b.w. intraperitoneal injection from days 13–18 of pregnancy), L-NAME?+?L-arginine (50?mg/kg b.w. and 1?g/kg b.w of L-arginine from days 13 to 18) and L-arginine (1?g/kg b.w administered orally from days 13 to 18). Urine samples were collected on day 18 of pregnancy and the animals were sacrificed on day 19 of pregnancy for blood pressure parameters, angiogenic and liver enzyme assays. L-NAME increased protein, albumin, systolic and diastolic blood pressure significantly when compared with control. This effect was reversed by L-arginine when co-administered with L-NAME (p?<?0.05). No difference was found in the pulse pressure and heart rate in all the groups as well as ALP and ALT levels. However, AST levels were significantly decreased in L-Arginine (L-Arg) administered rats when compared with control. VEGF and PIGF levels were decreased in the L-NAME administered rats, while this levels were increased in the L-NAME?+?L-Arg group and L-Arg group when compared with the L-NAME alone group (p?<?0.05). sVEGFR-1 level was increased in L-NAME administered rats when compared to control, while in the L-NAME?+?L-Arg group and L-Arg group the level of sVEGFR-1 was significantly decreased when compared to L-NAME alone group. This study showed that L-arginine supplementation in pregnancy reduced the preeclampsia-like symptoms exhibited by L-NAME in pregnant rats.     

一氧化氮在四磨汤诱导大鼠胃窦平滑肌收缩中的作用

背景：临床实践显示四磨汤具有全胃肠促动力效应。鉴于一氧化氮（NO）在胃肠神经介导胃肠平滑肌松弛中起重要中介作用,推测其可能参与了四磨汤对胃窦平滑肌收缩的调节。目的：研究NO在四磨汤诱导大鼠胃窦平滑肌收缩中的作用。方法：分别以梯度剂量（1~200μL）四磨汤和10-4mol/L NO供体左旋精氨酸（L-Arg）＋梯度剂量（1~200μL）四磨汤作用于大鼠离体胃窦纵肌条和环肌条,记录肌条基础状态和给药后收缩活动。结果：四磨汤能剂量依赖性地促进胃窦纵肌条和环肌条收缩（P=0.000）。经L-Arg预处理的胃窦纵、环肌条加入梯度剂量四磨汤后,肌条收缩活性量效曲线较单用四磨汤显著下移（L-Arg＋5~200μL四磨汤对单用5~200μL四磨汤,P均〈0.05）,表明NO可部分阻断四磨汤对胃窦平滑肌的兴奋效应。经L-Arg＋低中剂量（1~50μL）四磨汤作用的环肌条,收缩活性增幅显著低于纵肌条（P均〈0.05）。结论：四磨汤对大鼠胃窦平滑肌具有明显促收缩作用,该作用部分是通过抑制NO释放实现的。四磨汤对胃窦环肌的兴奋效应较纵肌更多依赖于抑制NO释放。     

复性液对单链免疫毒素细胞毒活性影响的研究

目的：研究复性液中各成分对免疫毒素细胞毒活性检测的影响。方法∶采用ＭＴＴ比色测定法对复性液中各主要成分的细胞毒性及其对免疫毒素细胞毒活性的影响进行检测分析。结果∶Ｌ—精氨酸具有明显的细胞毒性，与复性液及对照抗ＤＮＡ单链免疫毒素的细胞毒活性一致。结论∶复性液中Ｌ—精氨酸虽可减少免疫毒素的凝聚，增加其复性稳定性，但会影响细胞毒活性检测的精确度。