Objective To observe the effects of perfusion of rosiglitazone (RSG) in lesion areas on the expression levels of the perihematomal tight junction-associated proteins occludin and zonula occluden-1 (ZO-1) mRNA,the permeability of blood-brain-barrier (BBB),and neurological function score in a rabbit model of cerebral hemorrhage (ICH).Methods A total of 45 healthy male rabbits were selected (a body mass of 2.0 to 2.5 kg).They were divided into 3 groups,a control group,a ICH model group,and a RSG treatment group (n =15,5 of them for BBB determination) according to the random number table.The control group was use to simulate the process of making intracranial hematoma.After successful puncture,the target was iujected with isotonic saline 0.3 ml and isotonic saline 0.1 ml was injected again after 6 h;after successful puncture,the ICH model group was injected with 0.3 ml of autologous non-anticoagulant arterial blood,and the target was injected into isotonic saline 0.1 ml after 6 h;RSG 0.5 mg was infused into the hematoma area (dissolved in 0.1 ml isotonic saline) in the RSG treatment group at 6 h after the ICH model was successfully induced.All rabbits in each group were sacrificed on day 7 after the neurological deficit scale score (Purdy score).Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression levels of perihematomal oecludin and ZO-1 mRNA.The formamide method was used to measure the Evans blue (EB) content in the perihematomal tissue in order to evaluate the permeability of BBB.Results (1) Neurological function scores:Purdy scores of the control group,ICH model group,and RSG treatment group were 2.53 ± 0.05,8.13 ± 0.06),and 6.67 ± 0.08,respectively.There were significant differences among the groups (F =459.116,P ＜ 0.01).Compared with the control group,Purdy scores of the ICH model group and RSG treatment group were increased significantly (all P ＜ 0.01).Compared with the ICH model group,Purdy scores of the RSG treatment group were decreased (P ＜ 0.05).(2) The expression levels of occludin and ZO-1 mRNA:The differences were statistically significant in occludin and ZO-1 mRNA in the control group,ICH model group,and RSG treatment group (1.013 ±0.051,1.001 ± 0.045;0.221 ± 0.017,0.247 ± 0.019;0.498 ± 0.041,and 0.613 ± 0.045,respectively in each group;F =443.924 and 381.929 respectively,all P ＜ 0.01).Compared with the control group,the expression levels of occludin and ZO-1 mRNA were significantly decreased in the ICH model group and RSG treatment group (all P ＜ 0.01).Compared with the ICH model group,the expression levels of occludin and ZO-1 mRNA were increased in the RSG treatment group (all P ＜ 0.05).(3) The permeability of BBB:The EB content in the control group,ICH model group,and RSG treatment group were 12.0 ± 1.0,51.6 ± 0.9,and 36.4 ± 1.0 μg/g,respectively.The differences were statistically significant among the groups (F =223.516,P ＜ 0.01).Compared with the control group,the EB content was significantly increased in the ICH model group and RSG treatment group (all P ＜ 0.01).Compared with the model group,the EB content was significantly decreased in the RSG treatment group (P ＜ 0.01).Conclusion The perfusion of RSG in the lesion area can significantly improve the neurological function of rabbits after ICH,increase the expression levels of occludin and ZO-1 mRNA in the perihematomal tissue,and decrease the permeability of BBB.%目的 观察病灶区灌注罗格列酮(RSG)对家兔脑出血(ICH)模型血肿周围咬合蛋白和闭合小环蛋白l(ZO-1)mRNA表达水平、血-脑屏障(BBB)通透性及神经功能评分的影响. 方法 选择健康雄性家兔45只,体质量2.0 ～2.5 kg,按随机数字表法分为对照组、ICH模型组和罗格列酮(RSG)治疗组,每组15只(其中5只用于BBB测定).对照组模拟制作颅内血肿的过程,穿刺成功后对兔靶点注射等渗盐水0.3 ml,6h后再次注入等渗盐水0.1ml;ICH模型组穿刺成功后靶点注射自体非抗凝动脉血0.3ml,6h后靶点再次注入等渗盐水0.1 ml;RSG治疗组在ICH模型制作成功后6h,血肿区灌注RSG 0.5 mg(溶于0.1ml等渗盐水中).继续饲养至第7天,对各组家兔进行神经功能缺损评分(Purdy评分)后处死,逆转录聚合酶链反应(RT-PCR)法检测血肿周围脑组织咬合蛋白及ZO-1 mRNA的表达水平;采用甲酰胺方法测量血肿周围脑组织伊文思蓝(EB)含量以评估BBB通透性. 结果 (1)神经功能评分:对照组、ICH模型组、RSG治疗组Purdy评分分别为(2.53±0.05)、(8.13±0.06)、(6.67±0.08)分,组间差异有统计学意义(F=459.116,P＜0.01);与对照组比较,ICH模型组、RSG治疗组的Purdy评分均明显增加(均P＜0.01);与ICH模型组比较,RSG治疗组的Purdy评分降低(P＜0.05);(2)咬合蛋白及ZO-1 mRNA表达水平:对照组、ICH模型组、RSG治疗组咬合蛋白及ZO-1 mRNA差异均有统计学意义(每组分别为1.013±0.051、1.001 ±0.045;0.221 ±0.017、0.247±0.019;0.498±0.041、0.613 ±0.045;F值分别为443.924、381.929,均P＜0.01),与对照组比较,ICH模型组、RSG治疗组咬合蛋白及ZO-1 mRNA表达均显著减少(均P＜0.01);与ICH模型组比较,RSG治疗组咬合蛋白及ZO-1 mRNA的表达增加(均P＜0.05);(3)BBB通透性:对照组、ICH模型组、RSG治疗组EB含量分别为(12.0±1.0)、(51.6±0.9)、(36.4±1.0) μg/g,组间差异有统计学意义(F=223.516,P＜0.01);与对照组比较,ICH模型组、RSG治疗组的EB含量明显增加(均P＜0.01);与ICH模型组比较,RSG治疗组EB含量明显降低(P＜0.01).结论 病灶区灌注RSG可明显改善家兔ICH后的神经功能,增加血肿周围脑组织咬合蛋白和ZO-1mRNA的表达水平,降低BBB通透性.
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