氧自由基-线粒体信号通路在Edaravone治疗创伤性脑创伤中的作用  

Role of oxygen free radical-mitochondria signal pathway in Edaravone treating traumatic brain injury

作　　者：姚声涛[1] 唐文渊[1] 陈佳林[2] 郭川[1] 

机构地区：[1]重庆医科大学附属第一医院神经外科,400016 [2]贵州省遵义医院

出　　处：《中华创伤杂志》2008年第12期990-994,共5页Chinese Journal of Trauma

摘　　要：目的探讨创伤性脑损伤（traumatic brain injury，TBI）后在抗氧化剂Edaravone干预下大鼠大脑皮质凋亡相关蛋白表达改变情况并探讨氧自由基一线粒体信号通路在Edaravone治疗创伤性脑创伤中的作用。方法成年雄性sD大鼠180只随机分为TBI组、Edaravone治疗组和对照组。每组设伤后1，3，6，24，48，72h6个时相点。Edaravone治疗组给予Edaravone（10mg／kg），对照组、TBI组给予等量等渗盐水。HE染色观察大鼠TBI后皮层神经元的病理改变。免疫组化和TUNEL法以及硫代巴比妥酸缩合法观察不同时相点大鼠皮层Cyt—c、Bcl-2和Bax的表达情况，细胞凋亡和丙二醛（MDA）变化情况。结果HE染色可见创伤后6h大脑皮质出现散在变性坏死神经元，伤后24h达高峰。Edaravone治疗组伤后6h即可检测到自由基中间产物丙二醛（MDA）的升高，与对照组相比，48h达高峰。与TBI组相比，MDA含量各时相点均降低，其中在24，48和72h差异有统计学意义（P〈0．05）。与对照组相比，TBI组Cytc阳性细胞免疫反应6h增强，24h达高峰，在3，6，24，48和72h差异有统计学意义（P〈0．05）。与TBI组相比，Edaravone治疗组Ctyc阳性细胞免疫反应在24，48和72h降低。Bcl-2表达在伤后应激性增高，于3h达高峰，以后逐渐下降。Bax在伤后表达逐渐增高，于48h达高峰，Bax／Bcl-2于48h达高峰。TBI后，TUNEL阳性细胞数逐渐增多，24h以前以TUNELI型细胞为主，24h后以Ⅱ型细胞为主，并于48h达高峰。结论大鼠TBI后皮质神经细胞死亡存在坏死和凋亡两种方式，以凋亡为主。氧自由基-线粒体是TBI后神经细胞凋亡的信号转导通路中的一条。Edaravone对TBI有治疗作用。Objective To investigate the expression of apoptosis-related proteins in rat cerebral cortex following traumatic brain injuries （TBI） and discuss the role of oxygen free radical-mitochondria signal pathway in Edaravone treating TBI. Methods A total of 180 male adult Sprague-Dawley rats were randomly divided into TBI group, Edaravone treatment group and control group. Each group was divided into six subgroups at 1,3, 6, 24, 48 and 72 hours after TBI. Edaravone treatment group was injected with Edaravone （10 mg/kg） and the other two groups injected with the same volume of 0.9% normal saline. The pathological change in the rat cortex following TBI was observed with HE staining. At different time points, the expressions of Cytc, Bcl-2 and Bax in rat cortex as well as cell apoptosis and MDA change were observed by means of immunohistochemistry, TUNEL and TAB. Results HE staining showed scattered degenerated and necrotic neurons in cerebral cortex six hours after neuron injury, which peaked at 24 hours. Compared with control group, intermediate product MDA of free radical was increased six hours after TBI and peaked at 48 hours in Edaravone treatment group, which was lower than TBI group especially at 24, 48 and 72 hours （P 〈 0.05）. Compared with control group, the immunity reaction of Cyte positive cells increased at six hours and peaked at 24 hours in TBI group, with statistical difference at 3, 6, 24, 48 and 72 hours （P 〈 0.05）. Compared with TBI group, the immunity reaction of Cytc positive cells was decreased obviously at 24, 48 and 72 hours in Edaravone treatment group. Hyperexcitability of Bcl-2 after TBI reached peak at 3 hours and decreased gradually. But the expression of Bax was increased gradually after TBI and peaked at 48 hours, when Bax/Bcl-2 reached peak too. Following TBI, TUNEL positive cells increased gradually and reached peak at 48 hours, with mainly type I TUNEL cells before 24 hours and type Ⅱ TUNEL cells after 24 hours. Conclusions There exist necrosis and apoptosis of nerv

关 键 词：脑损伤 凋亡 自由基-线粒体信号通路 

分 类 号：R651.15[医药卫生—外科学]