摘要
目的 观察大鼠大脑皮质梗死后丘脑腹后外侧核（VPN）继发性损害机制,以及抗氧化剂依布硒啉对脑损伤的改善作用.方法 采用易卒中型肾血管性高血压大鼠（RHRSP）建立大脑中动脉闭塞（MCAO）模型.按随机数字表法将大鼠分为假手术组、模型组、溶剂组、依布硒啉组,每组8只.假手术组仅暴露大脑中动脉不结扎;溶剂组和依布硒啉组术后24 h分别灌胃0.5%羧甲基纤维素钠＋0.02%吐温20的溶剂或依布硒啉各5 ml/kg.2周后处死大鼠取脑组织,用苏木素-伊红（HE）染色观察VPN细胞形态;用免疫组化法观察无嘌呤无嘧啶核酸内切酶（APE）和大肠杆菌MutY DNA转葡萄糖基酶（MYH）两种DNA修复酶的表达.结果 HE染色显示依布硒啉可以改善皮质梗死所致的VPN细胞形态异常;免疫组化显示APE定位于VPN的胞核,MYH定位于VPN的胞质和胞核.模型组和溶剂组VPN的APE和MYH阳性细胞数（个）较假手术组显著减少（APE：57.0±14.7、49.4±12.5比101.0±13.6,MYH：15.0±4.7、10.4±2.5比56.0±13.2,均P＜0.05）;依布硒啉组APE和MYH阳性细胞数较模型组和溶剂组显著增多（APE：72.2±7.6比57.0±14.7、49.4±12.5,MYH：32.2±7.6比15.0±4.7、10.4±2.5,均P＜0.05）;模型组与溶剂组间APE和MYH阳性细胞数比较差异均无统计学意义.结论 实验性大鼠大脑皮质梗死后2周,VPN的DNA修复酶APE和MYH水平明显下降,抗氧化剂依布硒啉可明显升高其水平,从而阻止受损细胞死亡.
Objective To investigate the damage within the ventroposterior nucleus （VPN） of the thalamus after focal cortical infarction and its mechanism, and explore the effect of ebselen on the oxidative damage after cerebral cortex infarction in hypertensive rats. Methods Middle cerebral artery occlusion （MCAO） was induced in stroke-prone renovascular hypertensive rats （RHRSP）, and the rats were divided into four groups by table of random number： sham operation group, model group, vehicle group and ebselen group, each group consisted of 8 rats. In animals subjected to sham surgery the middle cerebral artery was exposed only. Ebselen （5 ml/kg） or vehicle （a mixed solvent consisting of 0. 5 % carboxymethyl cellulose and 0. 02% Tween 20, 5 ml/kg） was given by gastric gavage starting 24 hours after cerebral cortical infarction.Two weeks after the MCAO, the rats were sacrificed, and VPN from each group was sectioned and stained with hematoxylin-eosin （HE）, and apurinic/apyrimidinic endonuclease （APE） and Escherichia coli Mut Y DNA glycosylase （MYH） were determined by immunohistochemistry. Results HE staining showed that ebselen ameliorated the VPN damage induced by ischemia. Immunohistochemical imaging analysis revealed a distinct nuclear staining of APE and nuclear and cytoplasm distribution of MYH in the entire region of the VPN. Compared with sham operation group, the number of APE and MYH positive cells decreased in model group and vehicle group （APE： 57.0±14.7, 49.4±12.5 vs. 101.0±13.6, MYH： 15.0±4.7, 10.4±2.5 vs. 56. 0± 13. 2, all P〈0.05）. Compared with model group and vehicle group, the number of APE and MYH positive cells increased significantly in ebselen group （APE： 72. 2±7. 6 vs. 57. 0±14. 7, 49. 4±12. 5,MYH： 32. 2±7. 6 vs. 15.0±4.7, 10. 4±2.5, all P〈0. 05）; the difference of the number of APE and MYH positive cells between model group and vehicle group showed no statistical significance. Conclusion After 2 weeks of MCAO, there is a marked decrease of APE and MYH in VPN; ebselen can obviously increase the level of APE and MYH, and ebselen may protect the VPN of the thalamus from damage after focal cortical infarction in rats.
出处
《中国危重病急救医学》
CAS
CSCD
北大核心
2010年第10期587-590,I0001,共5页
Chinese Critical Care Medicine
基金
项目基金：国家自然科学基金项目（30770764,30271485）
河南省国际科技合作项目（084300510039）
河南省医药卫生重点项目（200702009）
河南省科技厅资金项目（072103810403）
关键词
脑梗死
丘脑腹后外侧核
DNA修复酶
抗氧化剂
大鼠
Cerebral infarction
Ventroposterior nucleus of the thalamus
DNA repair enzyme
Antioxidant
Rat
