摘要
应用线栓法经颈外-颈内动脉插线建立大脑中动脉闭塞再灌注(MCAO/R)大鼠动物模型,经颈内动脉单剂量注射1.5%神经调节素-1β(NRG-1β,0.3μg/kg)干预治疗。用干湿重法、免疫组化、免疫荧光双标记法和免疫印迹法观察NRG-1β对大鼠脑缺血再灌注损伤水通道蛋白(AQP-4)及胶质纤维酸性蛋白(GFAP)表达的影响。结果显示:随着缺血时间延长,对照组脑组织含水量逐渐增加,NRG-1β治疗能减少MCAO/R后脑组织含水量,与对照组相比,缺血1.5～2.0h组存在显著性差异(P<0.05)。脑缺血再灌注损伤可诱导脑组织AQP-4及GFAP表达,且随着缺血缺氧时间的延长,AQP-4及GFAP蛋白的表达逐渐增加。尽管它们均在胶质细胞中表达,但在脑组织中的分布略有不同。NRG-1β治疗可以增加二者在脑中的表达水平,与对照组相比具有显著性差异(P<0.01)。以上结果提示,NRG-1β可能通过激活内在的保护机制,增强胶质细胞的活性,从而抑制MCAO/R早期脑水肿的形成过程,改善神经元的生存环境,进而干扰脑缺血再灌注损伤的病理生理过程,对缺血性脑损伤具有积极的保护作用。
The animal models of middle cerebral artery oeclusion/reperfusion （MCAO/R） were established by monofilament method from the external-interual carotid artery in rats. A single dosage of 1.5% ncuregulin-1β（ NRG-1β,0.3 μg/kg） was injected from the internal carotid after）, （ICA） for treatment. The dry-wet weight compare, the immunohistochemical and immunnfluorescent double staining and Western blotting assay were used to determine the impact of NRG-1β nn the expressious of aquaporin-4 （AQP-4） and glial fibrillary acidic protein （GFAP） following cerebral ischemia/reperfusion. The resuhs showed that the brain water content increased in the control group with the duration of ischemia. NRG-1β treatment decreased the parameter. Compared with that in the control group, there were significant differences between the two groups at isehemia 1. 5 - 2.0 h （P 〈 0.05）. Cerebral ischemia/reperfusion injury induced the expressions of AQP-4 and GFAP in brain tissue and the alternations of the two proteins gradually elevated along with the increased ischemia time. Though the two proteins located mainly in gila, their distributions slightly varied iu brain regions. The administration of NRG-1β could increase the expressional level of AQP-4 and GFAP. Significant differences were found as compared with that in the control group （P 〈 0.01 ）. These results suggest that NRG-1β might inhibit the formation of early cerebral edema after MCAO/R, improve the microenvironment of neuron survival through activating the intrinsic protective mechanism and the glia function, turther disturb the patho-physiological process and play a protect role in ischemie cerebral insult.
出处
《神经解剖学杂志》
CAS
CSCD
北大核心
2009年第1期30-36,共7页
Chinese Journal of Neuroanatomy
基金
山东省自然科学基金(Y2004C04,Z2007D05)资助项目
