阿托伐他汀对脑外伤小鼠血脑屏障的影响  

Effect of atorvastatin on blood-brain barrier of traumatic brain injury mice

作　　者：金卫篷[1] 周源[2] 王东[2] 尉辉杰[2] 

机构地区：[1]天津医科大学第二医院神经外科,300211 [2]天津医科大学总医院神经外科

出　　处：《中华实验外科杂志》2015年第6期1361-1364,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学青年科学基金资助项目（81100920、81200907）;天津市应用基础及前沿技术研究计划资助项目（12JCQNJC07200、12JCQNJC06800）

摘　　要：目的 观察阿托伐他汀对脑外伤后小鼠血脑屏障的影响,探讨阿托伐他汀在脑外伤治疗中的作用.方法 将120只C57/BL6小鼠随机分为假手术组、生理盐水组和阿托伐他汀组,各40只.生理盐水组和阿托伐他汀组采用液压打击法制作脑外伤模型.假手术组不进行液压打击.阿托伐他汀组打击后1h予阿托伐他汀（每天1 mg/kg）灌胃,连续14 d.生理盐水组予等量生理盐水灌胃.造模后第1、3、7、14天对各组小鼠神经功能进行改良神经功能缺损评分（mNSS）;第1、3、7天干湿比重法检测脑组织水含量、Evans Blue法检测血脑屏障渗漏、免疫组织化学检测基质金属蛋白酶-9（MMP-9）水平;第3天Western blot检测紧密连接蛋白-5（Claudin-5）水平.结果 阿托伐他汀组小鼠第7、14天mNSS评分（分）明显低于生理盐水组（6.33±0.71比8.33±0.70、3.44±0.73比6.11 ±0.60,P＜0.05）.造模后第3天,阿托伐他汀组小鼠脑组织含水量[（80.06±0.15）％比（82.10±0.26）％]、Evans Blue（2.23±0.06比2.57 ±0.05）、Claudin-5检测值（0.61±0.01比0.29±0.01）与生理盐水组比较差异有统计学意义（P＜0.05）.造模后第3、7天阿托伐他汀组小鼠MMP-9阳性表达量与生理盐水组小鼠MMP-9阳性表达量比较显著降低（220.16±9.70比311.67 ±5.99、203.00±4.94比288.83±8.52,P＜0.05）.结论 阿托伐他汀能改善脑外伤小鼠神经功能,可能与阿托伐他汀对血脑屏障的影响相关.Objective 一o observe the effect of atorvastatin administration on the blood-brain barrier of traumatic brain injury （TBI） mice,and study the role of atorvastatin in the treatment of TBI.Methods 120 adult male C57/BL6 mice were randomly divided into the sham group,atorvastatin group and saline group,40 each.The atorvastatin group and saline group were given hydraulic combat to establish TBI models.The sham group mice underwent the same surgical procedure without being exposed to percussion injury.The atorvastatin group mice were treated with atorvastatin （orally,1 mg/kg） 1 h after TBI and then daily for 14 consecutive days.The saline group mice were given saline orally.The modified neurological severity scores （mNSS） test was conducted at 1st,3rd,7th and 14th day after TBI.Brain edema was measured at 1st,3rd,and 7th day after TBI.The leakage of blood-brain barrier was detected by Evans Blue method at 1st,3rd,and 7th day after TBI.The expression of matrix metalloproteinase-9 （MMP-9） was detected by immunohistochemical staining at 1 st,3rd,and 7th day after TBI,and that of Claudin-5 by Western blotting at 3rd day after TBI.Results The mNSS was statistically significant between atorvastatin group and saline group at 7th,and 14th day after TBI （6.33 ±0.71 vs.8.33 ±0.70,and 3.44 ±0.73 vs.6.11 ± 0.60,P＜0.05）.The content of water [（80.06±0.15）％ vs.（82.10±0.26）％],evans blue （EB,2.23 ±0.06 vs.2.57 ±0.05） and Claudin-5 （0.61 ±0.01 vs.0.29 ±0.01） showed statistically significant difference between atorvastatin group and saline group at 3rd day after TBI （P ＜ 0.05）.The MMP-9 was statistically significant between atorvastatin group and saline group at 3rd,and 7th day after TBI （220.16 ± 9.70 vs.311.67 ± 5.99,and 203.00 ± 4.94 vs.288.83 ± 8.52,P ＜ 0.05）.Conclusion Atorvastatin may improve neural function of TBI mice by influencing the blood-brain barrier.

关 键 词：阿托伐他汀 颅脑损伤 血脑屏障 

分 类 号：R651.15[医药卫生—外科学]