L-精氨酸对体外循环中红细胞保护作用的研究

目的：研究L－精氨酸（L-Arg)对体外循环（CPB）中红细胞的保护作用。方法：成年杂种犬12条，随机分为对照组（A组）和L－精氨酸组（B组），每组6条。两组动物均模拟临床开胸、建立体外循环、心肌缺血再灌注过程。B组于转机前静脉内注入L-Arg100mg/kg后，再持续静滴L-Arg10mg.kg^-1.min^-1至体外循环结束。分别于转前，并循5min，阻断15，45min，开放15，30min取静脉血测血浆一氧化氮（NO）代谢产物（NO^-2,NO^-3)、丙二醛（MDA）、游离血红蛋白（FHB）水平。结果：转机5min后的各时间段，B组的NO^-2、NO^-3水平显著高于A组，而血浆MDA及FHB水平显著低于C组。结论：L－精氨酸可使体外循环中血浆一氧化氮浓度明显增高，并使MDA、FHB浓度明显降低，因而能有效地保护CPB中红细胞。     

L-精氨酸对持续电刺激中缝隐核膈神经放电的影响

目的:研究L-精氨酸(L-Arginine,L-Arg)对持续电刺激中缝隐核(nucleus raphe obscurus,NRO)时膈神经放电的影响。方法:持续长时电刺激(5 min)成年家兔NRO,以膈神经放电为观察指标来观察其对呼吸的影响;将浓度为0.5、1.0、1.5、2.0mol·L~(-1)的L-Arg微量注射于NRO后,再持续电刺激NRO,观察和比较膈神经放电的变化。结果:持续长时电刺激NRO可导致膈神经放电的长时程增强,L-Arg不能引发膈神经放电的长时程增强,但可使持续刺激NRO时膈神经放电长时程增强的时间延长。结论:NRO对膈运动呼吸神经元的突触可塑性有重要作用,L-Arg参与NRO对呼吸节律的调整,表现为L-Arg可以维持但不能启动膈神经放电的长时程增强。     

Role of nitric oxide in the gastric cytoprotection induced by central vagal stimulation

The role of nitric oxide (NO) in the vagal cholinergic-mediated cytoprotective effect of intracisternal (i.c.) injection of the stable thyrotropin-releasing hormone (TRH) analog, RX 77368, was investigated in conscious rats. RX 77368 (1.5 ng i.c.) reduced by 88% gastric hemorrhagic lesions induced by oral administration of ethanol (60%). L-N^G-Nitro-arginine methyl ester (L-NAME, 3 mg/kg i.v.), an inhibitor of NO synthase, abolished the cytoprotection provided by i.c. RX 77368. The effect of L-NAME was reversed by L- but not D-arginine. These results suggest that the L-arginine-nitric oxide pathway is involved in the cytoprotective effect of i.c. TRH analog, probably through the modulation of gastric mucosal blood flow.     

Coconut kernel protein in diet protects the heart by beneficially modulating endothelial nitric oxide synthase,tumor necrosis factor-alpha,and nuclear factor-kappaB expressions in experimental myocardial infarction

Previous studies conducted in our laboratory revealed that coconut kernel protein has a significant cardioprotective effect on isoproterenol-induced myocardial infarction in rats. In the present study, we explored the possible protective mechanism of coconut kernel protein during acute myocardial infarction. Coconut kernel protein (50 mg/100 g) was administered to Sprague-Dawley rats orally for 45 days. Isoproterenol (20 mg/100 g) was injected subcutaneously at an interval of 24 hours twice to induce myocardial infarction. Myocardial infarction was confirmed by the abnormal activities of cardiac marker enzymes in serum. Activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase were decreased (p < 0.05) in the heart of isoproterenol-treated rats, whereas pretreatment with coconut kernel protein increased (p < 0.05) these activities. An improved antioxidant status in these rats was further confirmed by the increased level of reduced glutathione and decreased level of lipid peroxidation products. Nitric oxide synthase (NOS) activity in the heart and nitrite level in blood were increased (p < 0.05) in coconut kernel protein-treated rats administered with isoproterenol compared to isoproterenol control rats. Coconut protein pretreatment upregulated the expression of endothelial nitric oxide synthase (eNOS), whereas expressions of nuclear factor-kappaB (NF-κB) and tumor necrosis factor-alpha (TNF-α) were downregulated in isoproterenol-treated rats. These findings suggest that the protective effects of coconut kernel protein may be mediated in part through upregulation of nitric oxide production, antioxidant mechanisms, and its ability to inhibit TNF-α and NF-κB activation.     

L精-氨酸对失血性休克大鼠腹腔巨噬细胞功能的影响

目的:探讨左旋精氨酸(L-Arg)对失血性休克(HS)大鼠腹腔巨噬细胞(PMφs)功能的影响。方法:成年W istar大鼠随机分为对照组、HS组、生理盐水(NS)复苏组、L-Arg复苏组和L-Arg+N硝-基L精-氨酸甲酯(L-NAME)混合复苏组,每组10只。通过流式细胞术检测和评价PMφs的凋亡、吞噬凋亡细胞及主要组织相容性复合物Ⅱ(MHCⅡ)(I-A)表达能力的变化。结果:休克组与对照组之间PMφs的凋亡指数(AI)、吞噬能力和MHCⅡ(I-A)类抗原表达能力有显著性差异(P<0.01)。NS复苏组与休克组之间PMφs的AI、吞噬功能和MHCⅡ(I-A)表达能力均差异无显著性(P>0.05);L-Arg+L-NAME组与休克组之间PMφs的AI、吞噬功能和MHCⅡ(I-A)表达能力差异无显著性(P>0.05)。L-Arg组PMφs吞噬功能和MHCⅡ(I-A)表达能力显著高于休克组(P<0.05),而AI与休克组差异无显著性(P>0.05)。结论:L-Arg能改善HS后PMφs的吞噬功能和MHCⅡ的表达能力。     

L-Arginine Administration Reverses Anemia Associated with Renal Disease

Recombinant human erythropoietin (rhEpo) has proved to be remarkably safe and effective for the treatment of anemia. Despite the use of rhEpo, concerns about its cost, the need for frequent parenteral administration, and the development of anti-Epo antibodies have prompted the development of improved agents to rescue anemia. Patients with anemia associated with renal disease are usually treated by intravenous or subcutaneous rhEpo administration; however, some patients do not respond well to rhEpo, because of the presence of Epo antibody or other unknown reasons. A new, orally administered drug is needed as an economical and effective method to treat such patients. We administered 1.3 g/day of L-arginine to 8 elderly patients with anemia associated with renal disease. All 8 patients responded to the treatment with increases in hemoglobin levels. Six of the patients showed improved renal function. There were no significant adverse effects. Our data show that oral administration of 1.3 g/day of L-arginine significantly improves Epo production and reverses anemia without adverse effects in elderly patients who have anemia associated with renal disease and are in the predialysis state of chronic renal failure.     

Effects of endogenous nitric oxide induced by 5-fluorouracil and L-Arg on liver carcinoma in nude mice

AIM： To study the effects of endogeous nitric oxide induced by 5-fluorouracil （5-FU） and L-arginine （L-Arg） on the human liver carcinoma model in nude mice. METHODS： The human liver carcinoma model in nude mice was established with BEL-7402 cells and normal saline （NS）, 5-FU and 5-FU ＋ L-Arg injected intraperitoneally. The tumor size was measured. The necrotic degree and range were observed under microscope. The apoptosis of cancer cell was detected by turmina deoxynucleotidyl transferanse mediated dUTP nick end labeling （TUNEL） method. Immunohistochemical method was performed to determine the expression of iNOS, P16, BAX. The chemical colorimetry was used to test the activity and nitrate reductase method was adopted to test the concentration of nitric oxide （NO） in the tumor tissue. The BI2000 pathological image analyzer was used to analyze the result of immunohistochemistry. RESULTS： 5-FU combined with L-Arg could inhibit the tumor growth apparently. In NS, 5-FU and 5-FU＋L- Arg groups, the changes of tumor volumes were 257.978 ± 59.0, 172.232 ± 66.0 and 91.523 ± 26.7 mm3, respectively （P 〈 0.05 5-FU vs 5-FU ± L-Arg group;P 〈 0.05 NS ys 5-FU ± L-Arg group; P 〈 0.05, NS ys 5-FU group）. The necrotic range and apoptosis index were significantly increased after the drug injection. The necrotic range was biggest in 5-FU ＋ L-Arg group （X^2= 15.963, P 〈 0.05）. The apoptosis indexes were as follows： NS, 17.4% ± 6.19%; 5-FU, 31.3% ± 12.3%; and 5-FU ± L-Arg, 46% ± 15.24% （P 〈 0.05, 5-FU ys 5-FU ± L-Arg; P 〈 0.05, NS ys 5-FU ± L-Arg; P 〈 0.05, NS ys 5-FU）. The expression and activity of iNOS were increased in the tumor tissue. The concentration of NO was also increased. F of opticaldensity of iNOS, iNOS activity and NO concentration are 31.693, 21.949, and 33.909, respectively, P 〈 0.05. The concentration of NO was related to the expression of PI6 and BAX. The correlation coefficient was 0.764 and 0.554. CONCLUSION： 5-FU combined with L-Arg can inhi     

Effect of an L-arginine-reduced diet on proteinuria and hyperlipidemia in rats with anti-glomerular basement membrane nephritis

We examined whether or not elimination of L-arginine from a standard 20% casein diet would improve proteinuria and other symptoms in glomerulonephritic rats. Casein was enzymatically digested by trypsin and carboxypeptidase B. This enzymatical digestion of casein reduced the contents of L-arginine, L-lysine and L-histidine. The digested casein supplemented with L-histidine and L-lysine to the original casein levels was designated as enzymatically modified casein (EMC), and EMC supplemented with L-arginine to the original casein level as EMC+Arg. Male Wistar rats with glomerulonephritis induced by a single intravenous injection of nephrotoxic serum were fed either a 20% EMC+Arg (control) diet or 20% EMC (arginine-reduced) diet for 9 days. Nephritic rats fed the control diet showed not only proteinuria but also hyperlipidemia. Feeding EMC ameliorated proteinuria and hyperlipidemia without restriction of protein intake. These results suggest that trials to reduce dietary L-arginine even in standard protein diets have a remedial effect on the symptoms of glomerulonephritis.     

L—精氨酸促进移植血管诱导型一氧化氮合酶活性实验研究

目的：探讨外源性L－精氨酸（L－Arg)对移植血管诱导型一氧化氮合酶活性影响,方法：新西兰大白兔15只随机分成3组,建立双侧颈动脉间置颈外静脉移植动物模型,高剂量组每日喂食L－Arg 250mg/kg,低剂量组每日喂食L－Arg 125mg/kg,对照组不喂食L－Arg,持续2周,观察移植血管术前,术后3周和术后6周血浆一氧化氮（NO）水平,组织匀浆一氧化氮合酶（NOS）活性和诱导型NOS的mRNA表达。结果：（1）血浆NO水平：实验组血浆NO水平显著高于对照组,高剂量组血浆NO水平高于低剂量组。（2）组织匀浆NOS活性：实验组组织匀浆NOS活性显著高于对照组,3组术后6周NOS活性高于术后3周。（3）组织匀浆iNOS mRNA表达：术后3周实验组iNOS mRNA表达,对照组无表达;术后6周3组iNOS mRNA均有表达,实验组iNOS mRNA表达高于对照组,高剂量组高于低剂量组,结论：外源性L－Arg促进移植血管NOS表达,增进NOS活性,提高体内NO浓度。     

L-精氨酸对猫颅脑枪弹损伤早期脑微循环的影响

目的 研究猫在低速弹所致的颅脑枪弹损伤(CMW)后,L-精氨酸(L-Arg)对早期脑微循环的影响。方法 用改良Carey法制作猫CMW模型,将12只动物分为单纯损伤组和L-Arg治疗组,观察两组损伤前后软脑膜微血管的管径(D)、血流速度(V)、血流量(Q)及脑组织病理学的变化。结果 ①单纯损伤组,微动脉Da、Va和Qa在伤后5～20min期间明显降低,45min后逐渐恢复,并且Qa和Da超过伤前水平;微静脉Dv超过伤前水平但是无明显差异,而Vv伤后一直偏低,Qv在伤后20min内降低,45min后超过伤前呈淤血状态。②CMW后,L-Arg治疗组Da在5min时即出现扩张,Qa在20min后开始增加,一直持续到5h;Dv和Qv在20min后一致显著增加。③伤道对侧皮层可见点状出血、微血栓形成、神经细胞肿胀,L-Arg治疗组变化较单纯损伤组轻。结论 CMW后早期出现微循环障碍,导致脑缺血缺氧,引起神经功能障碍;注射L-Arg后,可以使微血管的管径和血流量增加,减轻颅脑损伤引起的脑微循环障碍和病理损害。