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[外源性一氧化氮供体及其酶促合成抑制剂对兔眼结膜静脉实验性缺血性血栓形成的影响]

[Effect of exogenous donors of nitric oxide and inhibitors of its enzymatic synthesis on experimental ischemic thrombosis in conjunctive veins of the rabbit eyes].

作者信息

Arkhipova M A, Mikoian V D, Vanin A F

出版信息

Biofizika. 2008 Mar-Apr;53(2):315-25.

Abstract

The beneficial action of dinitrosyl iron complex with glutathione on conjunctive veins of eyes in rabbits with experimental thrombosis of conjunctive veins has been demonstrated. Aqueous solutions of dinitrosyl iron complexes were added subconjunctively at doses of 5.4-8.1 micromole per eye. The average duration of thrombosis by the action of dinitrosyl iron complex decreased from 6.4 days in control animals to 2 days. The addition of dinitrosyl iron complex resulted in blood flow recovery in occlusive vessels and prevented ischemia and necrosis of tissues. The enhancement of hemorrhagic activity induced by dinitrosyl iron complexes was abrogated with combined addition of the nonselective NO synthase inhibitor N-nitro-L-arginine. In contrast, S-nitrosoglutathione affected adversely the veins: the duration of thrombosis in experimental thrombosis of conjunctive veins increased to 7 days. Intensive hemorhage developed in the conjunctive. The formation of protein-bound dinitrosyl iron complexes was observed by the EPR method in eye tissues after the subconjunctive or parabulbar addition of dinitrosyl iron complex with glutathione. This was not the case when the complex was injected intravenously. It was shown that dinitrosyl iron complex with glutathione induces the blockade of pellet aggregation or strengthens the fibrinolytic activity of plasma of patients with eye vessel pathology. The beneficial action of dinitrosyl iron complexes on conjunctive veins was proposed to be due to the capacity of dinitrosyl iron complexes to donate NO primarily to its biological targets. The release of free NO molecules in large amounts is not characteristic for dinitrosyl iron complexes. This process is characteristic of S-nitrosoglutathione, which sharply increases the probability of the accumulation of peroxynitrite, which produces a toxic effect on cells and tissues.

摘要

已证实二亚硝酰基铁配合物与谷胱甘肽对实验性结膜静脉血栓形成的家兔眼结膜静脉具有有益作用。以每只眼5.4 - 8.1微摩尔的剂量结膜下注射二亚硝酰基铁配合物的水溶液。二亚硝酰基铁配合物作用下血栓形成的平均持续时间从对照动物的6.4天降至2天。添加二亚硝酰基铁配合物可使闭塞血管恢复血流,并防止组织缺血和坏死。联合添加非选择性一氧化氮合酶抑制剂N - 硝基 - L - 精氨酸可消除二亚硝酰基铁配合物诱导的出血活性增强。相反,S - 亚硝基谷胱甘肽对静脉有不利影响:结膜静脉实验性血栓形成中血栓形成的持续时间增加到7天。结膜出现大量出血。通过电子顺磁共振方法观察到,在结膜下或球后添加二亚硝酰基铁配合物与谷胱甘肽后,眼组织中形成了蛋白质结合的二亚硝酰基铁配合物。静脉注射该配合物时则未出现这种情况。结果表明,二亚硝酰基铁配合物与谷胱甘肽可诱导血小板聚集受阻或增强眼部血管病变患者血浆的纤溶活性。二亚硝酰基铁配合物对结膜静脉的有益作用被认为是由于二亚硝酰基铁配合物主要向其生物靶点释放一氧化氮的能力。大量释放游离一氧化氮分子并非二亚硝酰基铁配合物的特征。这个过程是S - 亚硝基谷胱甘肽的特征,它会大幅增加过氧亚硝酸盐积累的可能性,而过氧亚硝酸盐会对细胞和组织产生毒性作用。

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