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CO是人体内类似于NO的信使分子,过渡金属羰基配合物是CO的固化形式。大量研究表明羰基钌一氧化碳释放分子(CORMs)具有很强的药理活性,本文合成了5个羰基钌CORMs,从毒理、组织分布及与血液内源性物质的相互作用等方面进行了研究。研究主要包含以下方面:①通过细胞生长抑制实验获得它们对成纤维细胞的IC50介于212.9~2 089.2μmol·L 1;利用小鼠测得它们的经口LD50介于800~1 600 mg·kg 1;血液生化分析及透射电镜检查表明多次给药后CORMs 1及CORMs 5对Wistar大鼠肝、肾功能无显著影响,但对肝肾组织细胞造成损伤。②小鼠腹腔给药后,以ICP-AES检测CORMs组织分布,结果表明羰基钌CORMs在体内主要分布于血液、肝、肾,在心、脾、肺中分布较少,不能通过血脑屏障进入脑组织;CORMs结构中的非CO配体对化合物的吸收分布有较大影响。③CORMs可使牛血清白蛋白的荧光增强,其强度与CORMs的加入量呈正比关系;CORMs与GSH的反应产物随条件不同而呈现二羰基钌或三羰基钌配合物两种形态。
CO is a messenger molecule similar to NO in the human body and the transition metal carbonyl complex is a cured form of CO. Numerous studies have shown that the carbonyl ruthenium and carbon monoxide release molecule (CORMs) has a strong pharmacological activity. In this paper, five CORMs of carbonyl ruthenium were synthesized, and the toxicological, tissue distribution and interaction with blood endogenous substances were studied. The study mainly includes the following aspects: ① The IC50 values of fibroblasts obtained from cell growth inhibition test ranged from 212.9 to 2089.2 μmol·L -1; their oral LD50 measured by mice ranged from 800 to 1 600 mg · kg -1 1; biochemical analysis of blood and transmission electron microscopy showed that CORMs 1 and CORMs 5 had no significant effect on the liver and kidney function of Wistar rats after multiple administrations, but damaged the liver and kidney cells. ② After intraperitoneal administration of mice, the distribution of CORMs was detected by ICP-AES. The results showed that the distribution of ruthenium carbonyl in the body mainly in the blood, liver and kidney, with less distribution in the heart, spleen and lung, and could not enter the brain through the blood-brain barrier Organization; non-CO ligands in CORMs structure have a greater impact on the absorption and distribution of compounds. ③CORMs can increase the fluorescence of bovine serum albumin, and its intensity is directly proportional to the amount of CORMs added. The reaction products of CORMs and GSH show two forms of dicarbonyl ruthenium or tricarbonyl ruthenium complex with different conditions.