氨基胍在大鼠蛛网膜下腔出血后早期脑损伤中的作用  

Aminoguanidine alleviates early brain injury after subarachnoid hemorrhage in rats

作　　者：杨鹏[1] 赵冬[1] 刘祺[1] 姬云翔[1] 朱立仓[1] 戴晶[1] 许晖[1] 唐仕军[1] 朱文学[1] 李晓天[1] 王业忠[1] 

机构地区：[1]石河子大学医学院第一附属医院神经外科,石河子医学硕士研究生832000

出　　处：《医学研究生学报》2015年第8期794-798,共5页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81360185);新疆建设兵团博士资金(2011BB016)

摘　　要：目的近期研究表明早期脑损伤是蛛网膜下腔出血患者死亡的首要原因,文中初步探讨氨基胍(aminoguanidine,AG)在蛛网膜下腔出血后早期脑损伤中起的作用。方法雄性SD大鼠68只,按照随机数字法分为4组:对照组(仅钻孔)、假手术组、蛛网膜下腔出血组、氨基胍组(分别钻孔并注入等渗盐水、股动脉血、股动脉血+AG),每组17只。视交叉前池注血法建立24 h大鼠蛛网膜下腔出血模型,HE染色鉴定模型。进行神经行为学评分(Garcia法),TUNEL法测神经元凋亡情况,Western blot检测诱导型一氧化氮合酶(inducible nitric oxide synthase,i NOS)蛋白、神经元特异性烯醇化酶(neuron-specific enolase,NSE)蛋白的表达。结果 HE染色结果显示蛛网膜下腔有较多红细胞存在。神经行为学评分显示蛛网膜下腔出血组分值[(14.47±0.62)分]较对照组[(17.94±0.24)分]、假手术组[(17.59±0.51)分]、氨基胍组[(15.71±0.47)分]显著降低(P<0.05)。TUNEL结果显示蛛网膜下腔出血组阳性细胞率[(42.38±2.38)%]较对照组[(6.35±0.94)%]、假手术组[(6.85±0.69)%]、氨基胍组[(30.48±2.89)%]显著升高(P<0.01);氨基胍组、对照组、假手术组阳性细胞率差异有统计学意义(P<0.05)。蛛网膜下腔出血组i NOS、NSE相对表达[(3.86±0.07)、(1.59±0.06)]较假手术组[(2.96±0.34)、(0.38±0.08)]、氨基胍组[(3.41±0.04)、(0.70±0.12)]、对照组[0,(0.35±0.09)]均显著升高(P<0.05)。各组i NOS、NSE蛋白表达量与TUNEL染色阳性细胞率均呈正相关(r=0.879、0.935,P<0.01)。结论在蛛网膜下腔出血后早期脑损伤中,AG可改善SD大鼠神经行为学功能,抑制神经元凋亡并下调i NOS、NSE的表达,具有减轻早期脑损伤的作用。Objective Recent studies have indicated that early brain injury is the leading cause of death in patients with subarachnoid hemorrhage （SAH）. Our study investigated the role of aminoguanidine （AG） in early brain injury after SAH. Methods Sixty-eight male SD rats were equally randomized into four groups of equal number： control, sham, SAH, and AG. The animals in the sham ~ouo were injected with isotonic saline solution, while those of the latter two groups with femoral artery blood （FAB） and FAB＋ AG, respectively, into the pre-chiasmatic cistern to induce SAH. At 24 hours after modeling, all the rats were killed for HE staining, obtainment of behavioral neurological assessment （BNA） scores by Garcia, measurement of the apoptosis of neurons by TUNEL, and de- termination of the expressions of the iNOS and NSE proteins by West- ern blot. Results The results of HE staining showed the presence of more red blood cells in the subarachnoid cavity of the rats in the SAH group, with a significantly decreased BNA score （14. 47 ±0.62） as compared with those in the control （17.94 ±0.24）, sham （17.59 ±0.51）, and AG group （15.71±0.47） （P 〈0.05）. The rate of positive cells was remarkably higher in the SAH group （ [42.38 ± 2.38 ] % ） than in the control （ [ 6.35± 0.94 ] % ）, sham （ [ 6.85± 0.69 ] % ）, and AG group （ [ 30.48 ± 2.89 ] % ） （ P 〈 0.01 ）, with significant differences among the latter three groups （ P 〈 0.05 ）. The expressions of iNOS and NSE were markedly higher in the SAH group （ [ 3.86 ±0.07 ] and [ 1.59 ± 0.06 ] ） than in the control （0 and [0.35 ±0.09]）, sham （[2.96 ±0.341 and [0.38±0.08]）, and AG group （[3.41 ±0.04] and [0.70 ±0.12] ） （P 〈0.05）. Both the expression levels of iNOS and NSE were positively correlated with the rate of positive cells （ r = 0. 879 and 0. 935, P 〈 0.01 ）. Conehmlon AG can alleviate early brain injury after SAH in SD rats by improving the neuro- ethologic function, suppressing

关 键 词：蛛网膜下腔出血 早期脑损伤 氨基胍 神经元特异性烯醇化酶 凋亡 

分 类 号：R651.1[医药卫生—外科学]