乌司他丁对治疗性低温用于心搏骤停大鼠脑复苏的改良作用  

Efficacy of ulinastatin for improvement of cerebral resuscitation using therapeutic hypothermia in rats with cardiac arrest

作　　者：仲浩[1] 惠康丽[2] 徐苗苗[2] 吴淋 高宇[2] 刘清珍[2] 段满林[2] 徐建国[2] 

机构地区：[1]徐州医科大学江苏省麻醉学重点实验室,221004 [2]南京军区南京总医院麻醉科,210002

出　　处：《中华麻醉学杂志》2016年第10期1261-1265,共5页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81671884）;天普研究基金（UF201407）;江苏省教育厅高校省级重点实验室开放课题（KJS1402）

摘　　要：目的探讨乌司他丁对治疗性低温用于心搏骤停大鼠脑复苏的改良作用。方法清洁级健康雄性SD大鼠60只，体重280-320g，采用随机数字表法分为5组（n=12）：假手术组（Sham组）、心搏骤停/心肺复苏组（CA／CPR组）、治疗性低温组（TI-I组）、乌司他丁组（U组）和乌司他丁＋治疗性低温组（U＋TH组）。采用经食道电刺激诱发心搏骤停，4min时行心肺复苏术的方法制备大鼠心搏骤停／心肺复苏模型。TH组于自主循环恢复即刻用乙醇涂擦大鼠体表，15min内将直肠温度降至32～34℃，维持6h；U组于自主循环恢复即刻经股静脉注射乌司他丁100000U／kg；U＋TH组于自主循环恢复即刻静脉注射乌司他丁100000U／kg并进行降温处理。于自主循环恢复后24和72h时进行神经功能评分；于自主循环恢复后72，h完成神经功能评分后，处死大鼠，取海马组织，光镜下观察海马CAl区病理学结果；采用免疫组织化学染色法和Westernblot法检测海马caspase-3的表达，Westernblot法检测海马Bax和Bcl-2的表达，计算Bax／Bcl-2比值。结果与Sham组比较，CA／CPR组自主循环恢复后神经功能评分降低，海马caspase-3和Bax表达上调，Bcl-2表达下调，Bax／Bcl-2比值升高（P〈0．05）；与CA／CPR组比较，TH组和U＋TH组自主循环恢复后24和72h时、U组自主循环恢复后24h神经功能评分升高，TH组、U组和U＋TH组自主循环恢复后72h时海马caspase-3表达下调，Bcl-2表达上调，Bax／Bcl-2比值降低，U组和U＋TH组海马Bax表达下调（P〈0．05）；与TH组或U组比较，U＋TH组自主循环恢复后24h时神经功能评分升高，自主循环恢复后72h时海马easpase-3表达下调，Bax／Bcl-2比值降低（P〈0．05）。U＋TH组海马组织病理学损伤较TH组或u组减轻。结论乌司他丁可改良治疗性低温对心搏骤停大鼠的脑复苏效果，机制可能与抑制神经元凋亡有关。Objective To investigate the efficacy of ulinastatin for improvement of cerebral resusci- tation using therapeutic hypothermia （TH） in rats with cardiac arrest （CA）. Methods Sixty pathogen- free healthy male Sprague-Dawley rats, weighing 280-320 g, were divided into 5 groups （n= 12 each） u- sing a random number table： sham operation group （group Sham）; CA/cardiopulmonary resuscitation （CPR） group （group CA/CPR）; group TH; ulinastatin group （group U）; ulinastatin ＋ TH group （group U＋TH）. CA was induced through transesophageal cardiac pacing, and CPR was performed at 4 rain of untreated arrest to establish CA/CPR model. In group TH, the rectal temperature was cooled down to32-34 ℃ by rubbing the body surface with ethanol within 15 min starting from the time point immediately after restoration of spontaneous circulation （ROSC） , and maintained at this level for 6 h. In group U, uli- nastatin 100 000 U/kg was injected via the femoral vein immediately after ROSC. In group U＋TH, ulinasta- tin 100 000 U/kg was intravenously injected immediately after ROSC, and rectal cooling was then started. The neurological function was evaluated and scored at 24 and 72 h after ROSC. The rats were sacrificed after the neurological function was scored at 72 h after ROSC, and the hippocampi were removed for microscopic examination of pathological changes in hippocampal CA1 region and for determination of caspase-3 expres- sion （by immunohistochemical staining and Western blot） and Bax and Bcl-2 expression （by Western blot） in hippocampal tissues. Bax/Bcl-2 ratio was calculated. Results Compared with group Sham, the neurological function score was significantly decreased, the expression of caspase-3 and Bax was up-regula- ted, the expression of Bcl-2 was down-regulated, and Bax/Bcl-2 ratio was increased after ROSC in group CA/CPR （P〈0.05）. Compared with group CA/CPR, the neurological function score was significantly in- creased at 24 and 72 h after ROSC in TH and U＋TH groups a

关 键 词：胰蛋白酶抑制剂 低温 人工 心脏停搏 心肺复苏术 脑 

分 类 号：R614[医药卫生—麻醉学]