l -精氨酸和氨基胍单独和联合给药治疗急性实验性腹膜炎的疗效观察

E. Husakouskaya, N. Maksimovich
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摘要

目标。目的:观察左旋精氨酸和氨基胍单独或联合给药治疗急性实验性腹膜炎的疗效。材料和方法。实验以白种雄性大鼠(185只)为实验对象,分为5个等量组,分别腹腔注射0.06 ml/100g:第1组(对照组)- 0.9%NaCl,第2组(实验性腹膜炎,EP) -第5组- 15%粪便悬浮液,第3组肌肉注射no -合成酶(NOS)底物- l -精氨酸,l -精氨酸(300mg/kg),第4组-诱导型NOS抑制剂-氨基胍,AG (15mg /kg),第5组- l -精氨酸和AG(类似剂量)。观察中毒综合征的体征、白细胞差异计数和腹膜液的变化、促氧化-抗氧化失衡的严重程度、血管内皮的病变和腹膜结构的改变。结果。与单用EP相比,l -精氨酸和AG联用EP对大鼠EP病程的研究显示,其纠正作用更为显著,表现为运动活动和肌肉力量增加,呼吸和体温调节正常化,白细胞增生严重程度降低,白细胞图核向左移动,吞噬活性增加,亚硝酸盐/硝酸盐和丙二醛浓度下降,还原型谷胱甘肽水平升高,血液循环内皮细胞数量减少,腹膜结构紊乱。结论。nos底物L-Arg及其诱导异构体抑制剂AG联合给药对EP大鼠最显著的纠正作用可能是由于AG抑制过量NO的产生,以及在给药过程中维持nos的组成活性和各种代谢途径。
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THE EFFECTS OF ISOLATED AND COMBINED ADMINISTRATION OF L-ARGININE AND AMINOGUANIDINE IN ACUTE EXPERIMENTAL PERITONITIS
Objectives. To study the effects of isolated and combined administration of L-arginine and aminoguanidine in acute experimental peritonitis. Material and methods. Experiments were conducted on white male rats (n=185), divided into 5equal series, which were injected intraperitoneally, 0,6ml/100g: the 1st series (control) - 0.9%NaCl, the 2nd (experimental peritonitis, EP) - the 5th series - 15% fecal suspension, with intramuscular injection to rats of the 3rd series with: substrate of NO-synthase (NOS) - L-arginine, L-Arg (300mg/kg), 4thseries - inhibitor of inducible NOS - aminoguanidine, AG (15 mg/kg), the 5th series - L-Arg and AG in analogous doses. The signs of intoxication syndrome, changes in leukocyte differential count and peritoneal fluid, the severity of prooxidant-antioxidant imbalance, lesions of vascular endothelium and structural changes in the peritoneum were studied. Results. The research of the EP course in rats with combined administration of L-Arg and AG revealed in the presence of more significant corrective effect, in comparison with the results in EP with their isolated use, showing up in the increase of motor activity and muscular strength, normalization of breathing and thermoregulation, decrease in the severity of leukocytosis and nuclear shift of the leukogram to the left, increase in the phagocytic activity, decline in the concentration of nitrite/nitrates and malondialdehyde, increased level of reduced glutathione, decrease in the quantity of circulating endothelial cells in blood and structural disorders in peritoneum. Conclusions. The most pronounced corrective effect of combined administration of the NOS-substrate, L-Arg, and the inhibitor of its inducible isoform, AG, in rats with EP may result from the suppression of excessive NO production by AG, as well as the maintenance of the constitutive NOS-activity and various metabolic pathways in the course of L-Arg administration.
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