塞来昔布对颅脑创伤后大鼠神经元凋亡的影响  

Effect of celecoxib on neuronal apoptosis after traumatic brain injury in rats

作　　者：李芳 邓玲 LI Fang;DENG Ling(Department of Ophthalmology, Xiangyang No. 1 People＇ s Hospital ,Hubei University of Medicine, Xiangyang 441030, Hubei Province, China;Department of Ophthalmology, Postgraduate Training Base, Jinzhou Medical University of Hubei University of Medicine, Xiangyang 441000, Hubei Province, China)

机构地区：[1]湖北医药学院附属襄阳市第一人民医院眼科,湖北襄阳441000 [2]锦州医科大学湖北医药学院研究生培养基地眼科,湖北襄阳441000

出　　处：《中国临床药理学杂志》2018年第10期1164-1167,共4页The Chinese Journal of Clinical Pharmacology

基　　金：河北省自然科学基金资助项目(C2004000689);河北省博士基金资助项目(05547008D-4);河北省科学技术与社会发展计划基金资助项目(04276135)

摘　　要：目的研究塞来昔布对大鼠颅脑创伤后核因子-κB(NF-κB)表达及神经元凋亡的影响及其作用机制。方法按照体重将SD大鼠随机分为3组,每组20只:假手术组、模型组、实验组。用改良的Feeney自由落体损伤装置构建大鼠颅脑创伤模型。造模成功后,实验组立即经腹腔注射塞来昔布250mg·kg^(-1),之后每隔8 h给药1次,共3 d;假手术组、模型组造模后不给于任何药物。以免疫组织化学法检测NF-κB、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)的表达;以原位末端标记法(TUNEL)检测神经细胞凋亡情况。结果假手术组、模型组、实验组的NF-κB(染色强度评分)分别为(1.61±0.45),(18.55±2.05),(7.70±1.34)分;这3组的Caspase-3蛋白表达(染色强度评分)分别为(1.91±0.52),(20.91±2.36),(11.91±1.27)分,模型组与假手术组比较,NF-κB与Caspase-3蛋白表达均显著增高,差异均有统计学意义(均P<0.05);实验组与模型组比较,NF-κB与Caspase-3蛋白表达均显著降低,差异均有统计学意义(均P<0.05)。假手术组、模型组、实验组的凋亡细胞数分别为5.91±1.25,28.60±3.23,10.91±2.40,模型组较假手术组凋亡细胞数增多,差异有统计学意义(P<0.05);实验组较模型组凋亡细胞数减少,差异有统计学意义(P<0.05)。结论塞来昔布通过下调颅脑创伤后NF-κB的表达从而调控抑制Caspase-3介导的凋亡程序,从而发挥对大鼠颅脑创伤后神经元的保护作用。Objective To study the effect of celecoxib on the expression of nuclear factor-κB(NF-κB） and neuronal apoptosis after traumatic brain injury(TBI） in rats,and to explore the protective effect of celecoxib on the neurons after traumatic brain injury and its mechanism. Methods SD rats were randomly divided into 3 groups(n = 3 in each group） ：sham operation group,model group and experimental group. Construction of a model of TBI in rats by modified feeney free fall injury device. The experimental group was injected intraperitoneally with celecoxib 250 mg·kg-1 immediately after successful modeling,and then administered once every 8 h for 3 d. Sham operation group,the model group did not give any drug treatment after modeling. The expression of NF-κB and Caspase-3 was detected by immunohistochemistry. Neuronal apoptosis was detected by terminaldeoxynucleotidly transferase mediated labeling(TUNEL）. Results The expression of NF-κB and Caspase-3 protein in sham operation group,model group and experimental group(dyeintensity score） were respectively(1. 61 ± 0. 45）,(18. 55 ± 2. 05）,(7. 70 ± 1. 34） point. The expression of Caspase-3 protein in the 3 groups(dye intensity score） were respectively(1. 91 ± 0. 52）,(20. 91 ± 2. 36）,(11. 91 ± 1. 27）point. The expression of NF-κB and Caspase-3 protein in model group was significantly higher than the sham operation group(all P〈0. 05）; compared with model group,the expression of NF-κB and Caspase-3 in experimental group were significantly decreased(all P〈0. 05）. The number of apoptotic cells in sham operation group,model group and experimental group were 5. 91 ± 1. 25,28. 60 ± 3. 23,10. 91 ± 2. 40. The number of apoptotic cells in model group was significantly higher than the sham operation group(P〈0. 05）; compared with the model group,the number of apoptotic cells in experimental group decreased significantly(P〈0. 05）. Conclusion Celecoxib inhibits Caspase-3-mediated apoptosis by down-regulating NF-κB,in order to achieve the

关 键 词：塞来昔布 创伤性脑损伤 核因子-ΚB 半胱氨酸天冬氨酸蛋白酶-3 凋亡 

分 类 号：R97[医药卫生—药品]