亚低温联合乌司他丁对大鼠局灶性脑缺血保护作用的实验研究  

Ulinastatin combined with sub-hypothermia protects focal cerebral ischemia in adult rats

作　　者：宋春红[1] 孙宇[1] 李启芳[1] 姜虹[1] 朱也森[1] 

机构地区：[1]上海交通大学医学院附属第九人民医院麻醉科,200011

出　　处：《上海医学》2008年第11期812-815,F0004,共5页Shanghai Medical Journal

摘　　要：目的探讨亚低温联合乌司他丁对脑缺血缺氧性损伤保护作用的可能机制。方法75只SD雄性大鼠随机分为对照(CN)组、缺血缺氧(IN)组、亚低温(IH)组、乌司他丁(INU)组和亚低温联合乌司他丁治疗(IHU)组,每组15只。用线栓法制成持续性大脑中动脉闭塞(MCAO)模型,CN组除不插入线栓外,余均同IN组;INU组、IHU组线栓成功后腹腔注射乌司他丁(5万U/kg),其他组注射等量0.9%氯化钠溶液;IH组、IHU组线栓成功及腹腔注射后即刻予2h亚低温(32～34℃)。缺血24h后,采用干湿重法检测大鼠脑组织含水量,生化检测超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)含量,原位末端标记法检测神经元凋亡表达。结果①CN组、IN组、IH组、INU组、IHU组的脑组织含水量分别为(79.94±0.22)%、(84.44±1.41)%、(80.66±0.96)%、(81.95±0.76)%、(79.74±1.16)%,IN组显著高于CN组(P<0.01),3个治疗组均显著低于IN组(P值均<0.05),IHU组又显著低于INU组和IH组(P值均<0.01)。②与CN组比较,IN组的脑组织MDA、NO含量显著升高(P值均<0.01),SOD含量显著降低(P<0.01);与IN组比较,IH组和INU组的脑组织MDA、NO含量显著降低(P值均<0.05),SOD含量显著升高(P值均<0.05);与IH组和INU组比较,IHU组的脑组织MDA、NO含量显著降低(P值均<0.05),SOD含量显著升高(P<0.05)。③IH组和INU组的缺血侧海马凋亡细胞计数显著少于IN组(P值均<0.05),IHU组又显著少于IH组和INU组(P值均<0.05)。结论脑缺血缺氧后即刻实施亚低温或腹腔注射乌司他丁均不同程度减轻大鼠脑损伤,两者联合应用则具有增强作用。Objective To investigate the mechanism by which ulinastatin （a trypsin inhibitor） combined with sub hypothermia protect hypoxic-ischemic brain damage in adult rats. Methods Seventy-five male SD adult rats were randomly divided into 5 groups： normal temperature control group （CN, n = 15）, hypoxic-ischemic （HI） in normal temperature group （IN, n=15）, HI in sub hypothermia treated group （IH, n=15）, HI in normal temperature with ulinastatin treated group （INU, n= 15）, and HI in sub-hypothermia combination with ulinastatin treated group （IHU, n= 15）. Middle cerebral artery occlusion （MCAO） model was created by ligation. Twenty-four hours after HI, the water contents in brain tissue were weighed. The apoptosis number, the contents of superoxide dismutase （SOD）, malondialdehyde （MDA） and Nitric Oxide （NO） were measured in cerebral tissue 24 hours after HI. Results The brain water contents in CN, IN, IH, INU and IHU were （79.94±0.22）%, （84.44±1.41）%, （80.66±0.96）%, （81.95±0.76）% and （79.74±1.16）%,respectively, with that of IN group significantly higher than that of CN group （P〈0.01）, those of the other 3 groups significantly lower in that of the IN group （all P〈0.05）, and that of the IHU group significantly lower than those of INU and IH groups （both P〈0.01）. Compared with the IN group, the contents of MDA and NO in cerebral tissue in the three treated groups were significantly decreased （P〈0.05）, and the activity of SOD was significantly increased （P〈0.05）. The apoptosis number in the IH and INU groups was significantly lower than that in the IN group （P〈0.05）, while significantly higher than tha in the IHU group （P〈0.05）. Conclusion Intraperitoneal administration of ulinastatin or sub-hypothermia can both reduce HI brain damage to different extents, and a combination of both has even stronger protective effect against brain damage.

关 键 词：脑缺血 脑缺氧 凋亡 亚低温 乌司他丁 

分 类 号：R743[医药卫生—神经病学与精神病学]