L—精氨酸对小鼠病毒性心肌炎心肌细胞的影响及其机理的探讨

目的：探讨Ｌ－精氨酸对病毒性心肌炎病理变化的影响。方法：将接种柯萨基病毒Ｂ３的Ｂａｌｂ／ｃ雄性小鼠随机分为饲服Ｌ－精氨酸组和对照组,于接种病毒后第５ｄ测小鼠血清ＮＯ（ＮＯ２／ＮＯ３）和ＣＫ－ＭＢ,心肌组织病理学改变和超微结构变化。结果：血清ＮＯ（ＮＯ２／ＮＯ３）和血清ＣＫ－ＭＢ,Ｌ－精氨酸组高于对照组;心肌组织病理学检查可见Ｌ－精氨酸组小鼠心肌细胞有程度不等的空泡变性和坏死,病理损伤较对照组严重;     

5-氟尿嘧啶联合L-精氨酸治疗裸鼠人肝癌移植瘤的研究

目的观察5氟尿嘧啶联合L精氨酸对裸鼠人肝癌移植瘤的作用并探讨其作用机制。方法采用BEL7402细胞株建立裸鼠人肝癌移植瘤模型,分别给裸鼠腹腔注射生理盐水,5氟尿嘧啶,5氟尿嘧啶+L精氨酸,观察各组药物对肿瘤的抑制作用,病理学观察移植瘤的坏死程度和范围,免疫组化测定移植瘤组织内诱导型一氧化氮合酶(iNOS)的表达。化学比色法检测诱导型一氧化氮合酶的活性。硝酸还原酶法检测瘤组织内的一氧化氮的浓度,统计分析采用SPSS10.0软件进行onewayANOVA,Bonferroni,KruskalWallisH检验。结果5氟尿嘧啶联合L精氨酸能明显增加对肿瘤生长的抑制作用,病理显示肿瘤的坏死范围增大,iNOS表达和活性增强,NO生成增加。结论5氟尿嘧啶联合L精氨酸能够抑制裸鼠人肝癌移植瘤的生长,其机制可能与诱导iNOS表达和活性增强,NO生成增加有关。     

原发性高血压患者血浆非对称性二甲基精氨酸浓度升高

背景非对称性二甲基精氨酸是一种内源性一氧化氮(NO)合成酶抑制剂,可以抑制NO的生成,影响血管内皮功能。目的探讨原发性高血压患者血浆非对称性二甲基精氨酸(ADMA)浓度的变化及可能意义。方法选取经冠状动脉造影检查排除冠状动脉粥样硬化性心脏病且无糖尿病的住院病人56例,其中原发性高血压(EH)患者30例,对照组(26例)为血压正常并无高血压史患者。通过高效液相色谱联合质谱法(HPLC)测定各患者的血浆ADMA、L精氨酸(L-Arg)含量,比色法测定血糖、肌酐、尿素氮、高密度脂蛋白胆固醇(HDL-C)、总胆固醇(TC)、三酰甘油(TG)和尿酸(UA)。结果EH组血浆ADMA浓度[(0.029±0.010)mmol/L]显著高于对照组[(0.023±0.010)mmol/L,P<0.05]。两组间血浆L-Arg、HDL-C、TC、TG、UA浓度比较,差异无统计学意义(P>0.05)。血浆ADMA、L-Arg浓度与患者年龄、HDL-C、TC、TG、UA浓度无相关性(P>0.05)。结论EH患者血浆ADMA浓度升高。     

PARADOXICAL DECREASE IN PLASMA NOx BY L-ARGININE LOAD IN DIABETIC AND NON-DIABETIC SUBJECTS

L-arginine, a substrate of nitric oxide synthase, was infused (30?g/300?ml/30?min) to patients with or without type 2 diabetes to examine whether or not endothelial dysfunction expressed as attenuated depressor response to the substrate in diabetic patients may accompany attenuated plasma NOx (NO₂^? and NO₃^?; an index of NO formation) elevation. Decrease in blood pressure by L-arginine was significantly smaller in diabetic patients than that in non-diabetic patients, and increase in plasma cGMP level in diabetic patients tended to be smaller and retarded than non-diabetic patients. However, plasma NOx decreased in both groups in a similar degree without changes in urinary NOx excretion, implying that NOx in plasma moved to other compartments. These results indicate that plasma NOx could not be solely used as an index of NO formation by L-arginine load and that this paradoxical decrease in plasma NOx would require further examination extending to other NOx compartments.     

Increased plasma nitric oxide, L-arginine, and arginase-1 in cirrhotic patients with progressive renal dysfunction

Background and Aims:  Increased levels of nitric oxide (NO) are hypothesized to contribute to renal dysfunction in patients with decompensated cirrhosis. In this study, we examined whether splanchnic and/or peripheral NO levels and L-arginine (L-Arg) correlate with progressive renal dysfunction in cirrhotics.
Methods:  Serum NO metabolites (NOx) and L-Arg were measured in: controls ( n  = 10); organ donors ( n  = 12); compensated cirrhotics ( n  = 17), cirrhotics with ascites ( n  = 25), refractory ascites ( n  = 11) or hepatorenal syndrome type II (HRS) ( n  = 11) and chronic renal failure patients ( n  = 18).
Results:  Plasma NOx and L-Arg levels rose progressively with worsening renal function in decompensated cirrhotics. Both NOx and L-Arg levels were highest in patients with HRS ( P  < 0.001 and P  < 0.025, respectively). While there were no differences in NOx levels related to the site of sampling, L-Arg levels were lowest in hepatic venous blood. There were significant relationships of NOx and L-Arg with Model for End-Stage Liver Disease score and Child–Pugh scores ( P  < 0.04 and P  < 0.01, respectively). Multivariate analysis showed a significant relationship between NOx, L-Arg and HRS.
Conclusion:  Worsening renal function in decompensated cirrhosis is accompanied by progressive elevation in plasma NOx and L-Arg. These findings support the hypothesis that NO-mediated vasodilation is probably linked with the mechanism of progressive renal failure in decompensated cirrhotics.     

L-精氨酸对L-NAME诱导的妊高征小鼠的影响

目的:采用一氧化氮合酶抑制剂建立小鼠妊高征模型,探讨L-精氨酸对妊高征孕鼠的作用效果及机制。方法:应用一氧化氮合酶抑制剂L-NAME复制小鼠妊高征模型,并采用L-精氨酸对妊高征孕鼠进行干预。观察血压、尿蛋白、胎鼠体重、胎盘重、胚胎死亡率、血浆及胎盘NO水平。结果:给予L-NAME可导致孕鼠血压升高,尿蛋白增加,仔鼠死胎率增加;L-精氨酸干预后能够显著增加NO合成,降低孕鼠尿蛋白和血压水平,胎盘和胎儿重量等发育指标得到改善。结论:NO合成不足是PIH发病的重要因素,L-精氨酸可以调节妊高征模型鼠体内血管舒缩平衡,促进滋养细胞及胎盘血管重建,改善子宫-胎盘-胎儿循环。     

Involvement of nitric oxide during<Emphasis Type="Italic">in vitro</Emphasis> fertilization and early embryonic development in mice

Nitric oxide (NO) has emerged as an important intracellular and intercellular messenger, controlling many physiological processes and participating in the fertilization process via the autocrine and paracrine mechanisms. This study investigated whether nitric oxide synthase (NOS) inhibitior (L-NAME) and L-arginine could regulate in vitro fertilization and early embryonic development in mice. Mouse epididymal spermatozoa, oocytes, and embryos were incubated in mediums of variable conditions with and without L-NAME or L-arginine (0.5, 1, 5 and 10 mM). Fertilization rate and early embryonic development were significantly inhibited by treating sperms or oocytes with L-NAME (93. 8% vs 66.3%, 92.1% vs 60.3%), but not with L-arginine. In contrast, fertilization rate and early embryonic development were conspicuously reduced when L-NAME or L-arginine was added to the culture media for embryos. Early embryonic development was inhibited by microinjection of L-NAME into the fertilized embryos in a dose-dependent manner, but only by high concentrations of L-arginine. These results suggest that a moderate amount of NO production is essential for fertilization and early embryo development in mice.     

川芎嗪联用左旋精氨酸对缺血-再灌注损伤兔肝脏能量代谢的影响

目的:探讨川芎嗪(LGT)、左旋精氨酸(L-Arg)联合使用对肝缺血-再灌注损伤(HIRI)时肝细胞能量代谢的影响及其机制。方法:实验兔40只,建立肝缺血-再灌注模型后随机分4组:模型组,LGT组,L-Arg组和LGT+L-Arg组,每组10只。再灌注45 min时,分别检测肝组织内三磷酸腺苷(ATP)、二磷酸腺苷(ADP)、一磷酸腺苷(AMP)含量、总腺苷酸量(TAN)、能荷(EC)、丙二醛浓度(MDA)、超氧化物歧化酶活性(SOD)、一氧化氮代谢产物(NO2-／NO3-)水平、血栓素B2(TXB2)、6-酮基-前列腺素F1α(6-keto-PGF1α)含量和TXB2／6-keto-PGF1α比值。结果:与模型组比较,LGT组、L-Arg组、LGT+L-Arg组肝组织内ATP、EC、NO2-／NO3-、6-keto-PGF1α含量及SOD活性均明显增高(P<0.05和P<0.01),MDA、TXB2含量及TXB2／6-keto-PGF1α比值均显著减少(P<0.05和P<0.01)。结论:LGT联用L-Arg可通过降低体内氧自由基水平、提高一氧化氮水平、纠正TXA2与PGI2的平衡,而改善缺血-再灌注损伤肝脏的能量代谢。     

TGF-alpha induces a stationary, radial-glia like phenotype in cultured astrocytes

The present study evaluated the role of nitric oxide (NO) in learned and innate fear in rats submitted to the elevated T-maze (ETM). Learned and innate fear were evaluated through the inhibitory avoidance and escape behaviour from the open arms, respectively. Rats treated with the inhibitor of NO synthesis N(omega)-nitro-L-Arginine methyl ester (L-NAME; 5, 10, and 50 mg. kg(-1)) were able to learn the inhibitory avoidance. However, L-NAME (50 mg. kg(-1)), but not its inert isomer N(omega)-nitro-D-arginine methyl ester (D-NAME, 50 mg. kg(-1)), impaired the inhibitory avoidance 2 with no change in the baseline values, thus suggesting an anxiolytic-like effect without locomotor impairment. All treatments with L-NAME were able to induce increased mean arterial pressure (MAP), measured indirectly through the animal's tail. The treatment with L-NAME (5 and 10 mg. kg(-1)) failed to induce anxiolysis but significantly increased the MAP of the animals, which indicates that hypertension per se, did not underlie anxiolysis induced by L-NAME. L-Arginine, the precursor molecule for NO synthesis, facilitated the inhibitory avoidance and counteracted the L-NAME (50 mg. kg(-1))-induced anxiolysis. Neither previous treatment was able to change the escape behaviour. The results indicate that NO may underlie learned, but not innate, fear in the ETM.     

血浆非对称二甲基精氨酸浓度与冠状动脉粥样硬化程度有关

目的探讨血浆非对称二甲基精氨酸(asymmetric dimethyl arginine,ADMA)浓度与冠状动脉粥样硬化程度的相关性。方法冠心病病人97例,经Judkins法行冠状动脉造影观察冠状动脉粥样硬化的程度,并参照Gensini积分系统分析冠状动脉造影结果,对照组为24例无动脉粥样硬化者;实验组为73例动脉粥样硬化者,根据Gensini积分的高低分为3个亚组。通过高效液相色谱联合质谱法方法测定血浆ADMA和L-精氨酸含量,比色法测定高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、总胆固醇、甘油三酯和尿酸。结果实验组ADMA浓度显著高于对照组[(5.5±1.3)μg/L与(4.4±0.9)μg/L(P<0.01)],ADMA/L-精氨酸低于对照组[(1.6±0.6)与(1.8±0.4)(P<0.05)],而两组间L-精氨酸差异无统计学意义。实验组亚组间分析显示随着Gensini积分的升高,血浆ADMA浓度上升。结论冠心病病人血浆ADMA浓度显著升高,与冠状动脉粥样硬化严重程度相关。