目的观察大鼠大脑皮质梗死后黑质的继发性损伤是否存在氧化损伤,并研究抗氧化剂依布硒对这种远隔部位损伤是否具有改善作用。方法按双肾双夹法制备易卒中型肾血管性高血压大鼠模型,12周后选择血压在24.0kPa以上、无自发性卒中症状的大鼠制备大脑中动脉闭塞(MCAO)模型。实验分5组:假手术组,模型组,溶媒组,依布硒10和30mg·kg^-1组。依布硒组大鼠MCAO后24h灌胃依布硒,每天1次,共13d。溶媒组给予等体积0.5%羧甲纤维素钠+0.02%吐温-20。末次给药后4h取黑质进行丙二醛(MDA)含量测定,取黑质网状核(SNR)进行HE染色,免疫组化检测SNR8-羟基-2-脱氧鸟苷(8-ohdG)阳性细胞数目。结果MCAO后2周,与假手术组比较,模型组黑质MDA含量增加;HE染色显示梗死同侧SNR细胞损伤,即核固缩;免疫组化显示8-ohdG阳性细胞数目增加。与溶媒组比较,依布硒10和30mg·kg^-1可抑制皮质梗死所致黑质MDA含量增加[(5.6±1.0)和(5.2±1.3)vs(8.2±1.7)μmol·g^-1湿组织],使皮质梗死所致萎缩的SNR细胞核增大。减少皮质梗死所致8-ohdG阳性细胞数目的增加(100±18和98±15绑127±18)。结论大脑皮质梗死2周后。梗死同侧黑质存在氧化性损伤,依布硒对黑质氧化损伤具有改善作用。
AIM To investigate the oxidative damage within the substantia nigra after focal cortical infarction in hypertensive rats, and explore the protective effect of ebselen against the damage. METHODS Middle cerebral artery occlusion (MCAO) was induced in rats with stroke-prone renovascular hypertension ( 〉 24.0 kPa) for 12 weeks, and the MCAO rats were randomly divided into 5 groups : sham operation group, ischemia group, solvent group, and ebselen 10 and 30 mg·kg^-1 groups. Ebselen (10 or 30 mg· kg^- 1 ) or solvent ( 0.5 % carboxymethyl cellulose + 0.02% Tween-20 ) was given (ig) 24 h after MCAO, once daily for 13 d. Four hours after the last administration, the concentration of malondialdehyde (MDA) in substantia nigra was measured and the substantia nigra pars reticulata (SNR) was sectioned and stained with hematoxylin-eosin staining. The number of 8-hydroxy-2'-deoxyguanosine (8-ohdG) positive cells was determined with immunohistochemistry assay. RESULTS Two weeks after MCAO, the level of MDA in sub- stantia nigra in ischemia group increased compared with the solvent group. HE staining showed that SNR cell damaged. SNR cells exhibited the characteristic morphological features of damage, i. e. , shrinkage of the nucleus. Immunohistochemistry indicated that the number of 8-ohdG positive cells increased. Compared with the solvent group, ebselen 10 and 30 mg· kg^-1 decreased the level of MDA in substantia nigra [(5.6±1.0) and (5.2±1.3) vs (8.2±1.7) μmol·g^-1 wet tissue 1, enlarged the nucleus of SNR cells, and decreased the 8-ohdG positive cells ( 100 ± 18 and 98 ±15 vs 127 ± 18 ). CONCLUSION The substantia nigra has been damaged 2 weeks after focal cortical infarction, and ebselen can protect the substantia nigra from oxidative damage .