Mechanism of protective effect of aminoguanidine on experimental cerebral ischemic injury in rats
- VernacularTitle:氨基胍对大鼠缺血性脑损伤的保护作用及其机制
- Author:
Huixin ZHANG
;
Jianxin ZHANG
;
Lanfang LI
;
Yonghui LI
- Publication Type:Journal Article
- Keywords:
brain ischemia;
nitric oxide;
aminoguanidine;
mitochondria;
cells,cultured
- From:
Chinese Journal of Pharmacology and Toxicology
2006;20(4):281-287
- CountryChina
- Language:Chinese
-
Abstract:
AIM To investigate the beneficial effects of aminoguanidine(AG), a selective inducible nitric oxide synthase (iNOS) inhibitor, on cerebral ischemic injury of rats and the possible mechanism. METHODS The middle cerebral artery occlusion model was prepared with thread embolism. AG 100 mg·kg-1 was injected ip first at 2, 6 and 12 h, respectively, after ischemia, then 2 times a day for 3 consecutive days. The infarct volume of brain tissue was determined with tetrazolium chloride staining. The mitochondria in brain tissue were isolated for measuring integrity of electron transport chain (ETC), mitochondrial swelling, NO and malondialdehyde (MDA) contents, ATPase, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. In addition, the neuronal cells of newborn rats were cultured in glucose-free medium with sodium hydrosulfite for cell viability, lactate dehydrogenease (LDH) and NO analysis. RESULTS AG significantly reduced infarct volume, ameliorated neuronal ultramicrostructural damages induced by ischemia. And the swelling of mitochondria, the lesions of ETC, the contents of MDA and NO in mitochondria were markedly decreased, the activities of ATPase, SOD and GSH-Px in mitochondria were increased. In vitro, compared with the ischemic group, AG(10, 20 and 100 μmol·L-1)increased the cell viability and reduced the contents of LDH and NO in culture medium. CONCLUSION AG has protective effects on cerebral ischemic injury through inhibiting the production of oxygen free radical, increasing antioxidation, ameliorating energy metabolism, and beneficially improving the integrity of structure and function of mitochondria in brain tissue.
