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动物模型中纳摩尔水平亚精胺对乳酸酸中毒的治疗作用

Lactic acidosis treatment by nanomole level of spermidine in an animal model.

作者信息

Sedigh-Ardekani Mozhgan, Sahmeddini Mohammad Ali, Sattarahmady Naghmeh, Mirkhani Hossein

机构信息

Department of Medical Physics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Nanomedicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran; Pharmaceutical Science Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Shiraz Anesthesiology and Intensive Care Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Regul Toxicol Pharmacol. 2014 Nov;70(2):514-8. doi: 10.1016/j.yrtph.2014.08.015. Epub 2014 Sep 6.

Abstract

Lactic acidosis occurs in a number of clinical conditions, e.g. in surgeries, orthotopic liver transplant, and anesthetic agent administration, which has deleterious effects on the patient's survival. The most rational therapy for these patients, the sodium bicarbonate administration, cannot prevent those accompanying deficiencies and may actually be harmful. In addition, tromethamine adjusts the blood pH, it does not affect the lactate accumulation. Therefore, discovery of a therapeutic agent is still a major unsolved problem. In this study, the rats were divided into different groups and lactic acidosis type B was induced in them. Then, the effect of different injection doses of spermidine (0-20nmol) on lactic acidosis was analyzed by measuring the lactate level and pH in the rat blood samples. The results showed that spermidine effectively and simultaneously inhibited the lactate and pyruvate accumulations, and also adjusted the pH of bloodstream. On the other hand, it has been shown (Damuni et al., 1984; Rahmatullah and Roche, 1988) that spermidine increases the activity of phosphatase, leading to prevention of lactate accumulation. The results indicate that administration of only nanomole level of spermidine may be the best treatment in the liver transplant and other patients suffering from lactic acidosis type B.

摘要

乳酸性酸中毒发生于多种临床情况,例如手术、原位肝移植及麻醉剂给药过程中,这对患者的生存具有有害影响。针对这些患者最合理的治疗方法,即给予碳酸氢钠,并不能预防伴随的缺陷,实际上可能还有害。此外,三羟甲基氨基甲烷可调节血液pH值,但不影响乳酸的积累。因此,发现一种治疗药物仍然是一个主要的未解决问题。在本研究中,将大鼠分为不同组并诱导其发生B型乳酸性酸中毒。然后,通过测量大鼠血液样本中的乳酸水平和pH值,分析不同注射剂量(0 - 20nmol)的亚精胺对乳酸性酸中毒的影响。结果表明,亚精胺有效且同时抑制了乳酸和丙酮酸的积累,还调节了血液pH值。另一方面,已有研究表明(达穆尼等人,1984年;拉赫马图拉和罗氏,1988年)亚精胺可提高磷酸酶的活性,从而防止乳酸积累。结果表明,仅给予纳摩尔水平的亚精胺可能是肝移植及其他患有B型乳酸性酸中毒患者的最佳治疗方法。

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