环孢菌素A早期应用对实验性脑出血大鼠的神经保护作用  

Early administration of cyclosporin A providing neuroprotection in experimental rats with cerebral hemorrhage

作　　者：张海旺 张苓 王斌 李昊 黄昌仁 明扬 董劲虎 杨福兵 江涌 刘亮 夏祥国 冯华[2] 陈礼刚 

机构地区：[1]四川医科大学附属医院神经外科,泸州646000 [2]第三军医大学附属西南医院神经外科,重庆400038

出　　处：《中华神经医学杂志》2015年第11期1100-1105,共6页Chinese Journal of Neuromedicine

基　　金：国家重点基础研究发展计划（973计划）资助项目（2014CB541606）;国家自然科学基金（81371319）

摘　　要：目的探讨环孢菌素A（CsA）早期应用对实验性脑出血大鼠的神经保护作用。方法将96只雄性SD大鼠按随机数字表法分为假手术组、脑出血＋溶剂组、脑出血＋CsA5mg组和脑出血＋CsA10mg组共4组，每组各24只。后3组抽取100肌L右侧股动脉自体血注入有侧基底节区制作成脑出血模型，并对脑出血＋CsA5mg组和脑出血＋CsA10mg组大鼠于术后15min经尾静脉给药（5mg／kg、10mg／kg），而后每24小时1次。术后24h对各组大鼠行小动物头颅MRI检查，采用干湿重法检测脑组织含水量，采用伊文思蓝（EBl法检测血脑屏障通透性；术后72h对各组大鼠采用NISSL染色、TUNEL染色检测细胞凋亡并进行神经功能评分。结果术后24h头颅MRI检查显示脑出血＋溶剂组血肿周围脑组织脑水肿较假手术组明显加重，脑组织含水量（79．55％±0．09％）较假手术组（78．22％±0．14％）明显升高，EB含量[（5．53±0．26）μg/g]较假手术组[（2．55±0．13）μg／g]明显升高，差异均有统计学意义（P〈0．05）；术后72hNISSL染色示脑出血＋溶剂组血肿周围脑组织细胞显著减少，凋亡细胞数（180．00±12．43）较假手术组（26．00±．29）显著增多，神经功能评分较假手术组明显降低，差异均有统计学意义（P〈0．05）。术后24h头颅MRI检查显示脑出血＋CsA10mg组血肿周围组织脑水肿较脑出血＋溶剂组、脑出血＋CsA5mg组明显减轻，脑组织含水量（78．70％±0．07％）较脑出血＋溶剂组、脑出血＋CsA5mg组（78．91％±0．11％）明显降低，EB含量[（3．24±0．16）μg/g]较脑出血＋溶剂组、脑出血＋CsA5mg组[（4．12±0．12）μg／g]明显降低，差异均有统计学意义（P〈0．05）：术后72hNISSL染色示脑出血＋CsA10mg组细胞减少不明显，凋亡细胞数（69．33±11.31）较脑出血＋溶剂组、脑出血＋CsA5mg组（95．00±8．99）明显减少，神经功能评分较�Objective To assess the impact of early administration of cyclosporine A （CsA） in neuroprotection in experimental rats with intracerebral hemorrhage （ICH）. Methods Ninety-six male SD rats were randomly divided into sham-operated group, ICH＋vehicle group, ICH＋CsA 5 mg group and ICH＋CsA 10 mg group （n=24）. And 100 mL autologous blood from the right femoral artery was injected into the right basal ganglia to induce ICH models in the later three groups. Tail vein administration of 5 mg/kg and 10 mg/kg CsA was performed in the later two groups 15 min after ICH, and then, once every 24 h. Twenty-four h after ICH, MR imaging was performed; brain water content was measured by Wet and dry weight method; blood-brain barrier permeability was detected by Evans blue （EB） method. Seventy-two h after ICH, NISSL and TUNEL were employed to detect the cell apoptosis, and neurological deficit scale scores were recorded. Results Twenty-four h after ICH, ICH＋vehicle group had significantly severer cerebral edema, significantly increased water content of brain tissues （79.55%±0.09%） and EB content （[5.53±0.26] μg/g） as compared with sham-operated group （78.22%±0.14%, [2.55±0.13] μg/g）, with significant differences （P〈0.05）; ICH＋CsA 10 mg group had significantly alleviated cerebral edema, significantly decreased water content of brain tissues （78.70%±0.07%） and EB content （[3.24±0.16] μg/g） as compared with ICH＋vehiele group and ICH＋CsA 5 mg group （78.91%± 0.11%, [4.12±0.12] μg/g）, with significant differences （P〈0.05）. Seventy-two h after ICH, ICH＋vehiele group had decreased number of brain tissue cells around the hematoma, increased apoptosis cells （180.00± 12.43） and decreased neurological deficit scale scores as compared with sham-operated group （26.00±7.29）, with significant differences （P〈0.05）; ICH＋CsA 10 mg group had decreased apoptosis cells （69.33± 11.31） and increased neurological deficit scale scores as compared with ICH�

关 键 词：脑出血 环孢菌素A 脑水肿 血脑屏障 神经元凋亡 

分 类 号：R743.3[医药卫生—神经病学与精神病学]