2-(2-苯并呋喃基)-2-咪唑啉对大鼠心肺复苏后的脑保护作用  

Protective Effect of 2-(2-Benzofu-ranyl)-2-imidazoline on Brain after Cardiopulmonary Resuscitation in Rats

作　　者：杨婷[1] 徐莎莎 陈轲扬[2] 韩钊[2] 曹云刚[2] Yang Ting;Xu Shasha;Chen Keyang;Han Zhao;Cao Yungang(Department of Emergency,the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang Wenzhou 325000,China;Department of Neurology,the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Zhejiang Wenzhou 325000,China)

机构地区：[1]温州医科大学附属第二医院急诊科,浙江温州325000 [2]温州医科大学附属第二医院神经内科,浙江温州325000

出　　处：《中国药师》2021年第6期997-1000,1012,共5页China Pharmacist

基　　金：国家自然科学基金项目(编号:81771267);温州市基础性科研项目(编号:Y2020527)。

摘　　要：目的:观察大鼠心肺复苏后脑能量代谢变化及新型N-甲基-D-天冬氨酸受体拮抗剂2-(2-苯并呋喃基)-2-咪唑啉(2-BFI)的脑保护作用机制。方法:120只成年雄性大鼠按随机数字表法分为假手术组、常规复苏组和2-BFI组,其中常规复苏组和2-BFI组建立心脏骤停/心肺复苏模型。待自主循环恢复后,2-BFI组股静脉注射2-BFI 3 mg·kg^(-1),假手术组和常规复苏组股静脉注射等量生理盐水。各组分别于0.5,3,6,12,24 h取材,每个时间点8只,采用HPLC法测定组织腺苷酸含量,HE染色观察大脑皮层病理变化,分光光度法测定ATP酶活性。结果:各组间大鼠体质量、肾上腺素用量、平均动脉压(MAP)、胸外按压时间参数等比较差异均无统计学意义(P>0.05)。与常规复苏组比较,2-BFI组的5’-ATP、EC和TAN于24 h显著升高,5’-AMP显著下降(P<0.05或P<0.01);6,12,24 h的Na^(+)-K^(+)-ATP酶和Ca^(2+)-Mg^(2+)-ATP酶活性均显著升高(P<0.01)。与0.5 h比较,常规复苏组和2-BFI组24 h的5’-ATP、5’-AMP、TAN、EC差异均有统计学意义(P<0.05或P<0.01);12 h和24 h的Na+-K+-ATP酶和Ca^(2+)-Mg^(2+)-ATP酶活性差异有统计学意义(P<0.01)。假手术组各时间点形态结构清晰,神经细胞无肿胀;常规复苏组在6 h后,脑组织细胞坏死,细胞体积缩小,胶质细胞周围间隙扩大,血管周围有大的空白区域及细胞碎片,结构稀疏,见核固缩、深染等细胞缺血坏死表现;2-BFI组6 h后核周间隙扩大,较少坏死空泡区,胶质细胞轻度水肿。结论:大鼠心肺复苏后存在脑能量代谢障碍,2-BFI能改善脑能量代谢,减轻脑再灌注损伤,具有脑保护作用。Objective:To observe the changes of brain energy metabolism after cardiopulmonary resuscitation in rats and the mechanism of brain protection of new N-methyl-D-aspartate receptor antagonist 2-(2-benzofuryl)-2-imidazoline(2-BFI).Methods:Totally120 adult male rats were divided into sham operation group,conventional resuscitation group and 2-BFI group according to the random number table method.Among them,the conventional resuscitation group and 2-BFI group were established a cardiac arrest/cardiopulmonary resuscitation model.After the spontaneous circulation was restored,2-BFI group was injected 2-BFI 3 mg·kg^(-1) into femoral vein,and the sham operation group and the conventional resuscitation group were injected with the same amount of normal saline.In each group,samples were taken at 0.5,3,6,12 and 24 h with 8 rats at each time point.The adenylate content of tissue was determined by HPLC,the pathological changes of cerebral cortex were observed by HE staining,and ATPase activity was determined by spectrophotometry.Results:There were no significant differences in rat’s body weight,adrenaline dosage,mean arterial pressure(MAP)and chest compression time parameters among the groups(P>0.05).Compared with those in the conventional resuscitation group,the 5’-ATP,EC and TAN of 2-BFI group increased significantly at 24 h,and 5’-AMP decreased significantly(P<0.05 or P<0.01);the activities of Na^(+)-K^(+)-ATPase and Ca^(2+)-Mg^(2+)-ATPase at 6,12 and 24 h increased significantly(P<0.01).Compared with those at 0.5 h,the differences in 5’-ATP,5’-AMP,TAN and EC at 24 h between the conventional resuscitation group and 2-BFI group were statistically significant(P<0.05 or P<0.01);the differences between the activities of Na+-K+-ATPase and Ca^(2+)-Mg^(2+)-ATPase at12 h and 24 h were statistically significant(P<0.01).The sham operation group had clear morphology and structure at each time point,and there was no swelling of nerve cells;in the conventional resuscitation group,6 hours later,the brain tissue cells were necr

关 键 词：2-(2-苯并呋喃基)-2-咪唑啉 心脏骤停 心肺复苏 脑损伤 三磷酸腺苷酶 

分 类 号：R965.1[医药卫生—药理学]