罗格列酮病灶区灌注对脑出血家兔继发脑损伤的预防作用观察及机制探讨  

Preventive effect of rosglitazone infusion on rabbits with secondary brain injury after intracerebral hemorrhage

作　　者：李军 叶飞 王丽琨 任思颖 伍国锋 LI Jun;YE Fei;WANG Likun;REN Siying;WU Guofeng(The Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China)

机构地区：[1]贵州医科大学附属医院

出　　处：《山东医药》2020年第6期45-49,共5页Shandong Medical Journal

基　　金：贵州省科技厅联合基金资助项目(黔科合LH字[2017]7187)

摘　　要：目的观察罗格列酮病灶区灌注对脑出血家兔继发性脑损伤的预防作用,并探讨预防机制。方法45只健康家兔随机分为对照组、模型组及罗格列酮组,各15只。模型组和罗格列酮组在基底节区注入自体耳缘静脉血制备基底节区脑出血模型,对照组在基底节区注入生理盐水;6 h后,罗格列酮组给予罗格列酮病灶区灌注,对照组和模型组给予等量生理盐水灌注。分别在灌注后的第1、3、7天采用Purdy评分评估三组神经功能,同时通过病灶周围脑组织伊文思蓝含量评估血脑屏障通透性、干湿称重法测定脑组织含水量,采用HE染色观察各组病灶周围脑组织神经细胞、神经胶质细胞形态,采用免疫组化法检测各组病灶周围脑组织AQP-4。结果与对照组比较,模型组灌注后第3、7天Purdy评分均升高、病灶周围脑组织含水量增加,且灌注后第3天达高峰,各时间点病灶周围脑组织伊文思蓝含量均高(P均<0.05);与模型组比较,灌注后第3、7天罗格列酮组Purdy评分均低、病灶周围脑组织含水量减少,各时点病灶周围脑组织伊文思蓝含量均低(P均<0.05)。对照组各时点病灶周围脑组织中神经细胞和胶质细胞形态正常,模型组病灶周围脑组织出现脑损伤表现,罗格列酮组与模型组比较脑组织病灶周围脑损伤表现减轻。各时间点,与对照组比较,模型组AQP-4表达量升高,与模型组比较,罗格列酮组AQP-4表达量降低(P均<0.05)。脑出血家兔病灶周围脑组织AQP-4表达与脑组织含水量、脑组织伊文思含量、Purdy评分呈正相关性(P均<0.01)。结论罗格列酮病灶区灌注可以减轻家兔脑出血后继发脑损伤,可能与其降低病灶周围脑组织AQP-4表达有关。Objective To observe the effects of infusing rosiglitazone into the focal area on perihematomal secondary brain damages in rabbit models with intracerebral hemorrhage(ICH)by taking blood-brain barrier(BBB)permeability,brain water content and AQP-4 as indexes.Methods Forty-five rabbits were assigned to the normal control group(NC group),model control group(MC group),and rosiglitazone infusion therapy group(RSG group),with 15 rabbits in each.For the MC group and the RSG group,the models of ICH were established by injection of autologous blood into the basal ganglion.In the NC group,however,the same amount of normal saline was injected into the basal ganglia as control.Six hours later,the RSG group received injection of rosiglitazone into the hematoma.The NC group and the MC group,however,received only the same amount of normal saline into the hematoma.Each group was divided into three subgroups which included five rabbits.The neurological function was determined by Purdy score on day 1,3,and 7 after the successful establishment of ICH model.The animals were sacrificed on day 7,and then the BBB permeability was measured by determining the content of perihematomal Evans blue.The brain water content was determined by the method of dry-wet weight.The morphological changes of the glial cells and the neurons were observed by HE staining.The immunohistochemical method was used to determine the perihematomal AQP-4 level.Results Compared with the NC group,the Purdy scores increased on day 3 and 7 in the MC group and the RSG group.The BWC and the level of the Evans blue showed similar changes.Compared with the MC group,however,the Purdy scores decreased on day 3 and 7,as well as the BWC and the Evans blue content.The up-regulation of AQP-4 was observed in the MC group at each time point as compared with that of the NC group.However,the AQP-4 expression was down-regulated in the RSG group as compared with the MC group.The increased AQP-4 was positively correlated with the BBB permeability,the BWC and the Purdy scores(all P<0.

关 键 词：罗格列酮 出血后继发脑损伤 脑出血 水通道蛋白-4 

分 类 号：R741[医药卫生—神经病学与精神病学]