摘要
目的探讨拉莫三嗪对脑外伤大鼠学习记忆能力及核因子(NF)-κB信号通路的影响。方法选取SPF级健康雄性SD大鼠,随机分为对照组、假手术组、模型组和低、中、高剂量实验组,每组15只。模型组和低、中、高剂量实验组用Feeney自由落体脑损伤装置造模,假手术组只切开皮肤和暴露颅骨,对照组不做任何处理。低、中、高剂量实验组分别予以灌胃20,30,60 mg·kg^-1拉莫三嗪,对照组、假手术组和模型组则予以等体积NaCl,每日1次,共2周。大鼠脑外伤后进行水迷宫定位航行实验测定其学习记忆能力,用末端标记法(TUNEL)法检测神经细胞凋亡,用实时荧光定量聚合酶链反应(qRT-PCR)检测脑组织中NF-κB、B淋巴细胞瘤-2(Bcl-2)、兔抗人单克隆抗体人Bcl-2相关X蛋白(Bax)、胱天蛋白酶-1(caspase-1)mRNA表达。结果对照组、假手术组、模型组和低、中、高剂量实验组第11天逃避潜伏期分别为(13.16±2.83),(15.53±2.71),(68.21±3.44),(50.06±2.95),(46.31±2.41)和(34.62±2.20)s;细胞凋亡率分别为(1.10±0.08)%,(1.21±0.11)%,(4.73±0.34)%,(2.80±0.22)%,(2.27±0.14)%,(1.91±0.20)%;NF-κB mRNA分别为0.82±0.05,1.06±0.08,2.87±0.42,2.01±0.18,1.83±0.12,1.75±0.10;Bcl-2 mRNA分别为1.12±0.17,0.81±0.09,0.23±0.03,0.30±0.05,0.35±0.07,0.67±0.08;Bax mRNA分别为0.96±0.04,1.64±0.23,5.03±0.31,3.77±0.16,2.24±0.08,1.97±0.25;caspase-1 mRNA分别为1.01±0.04,1.75±0.18,8.91±0.36,4.93±0.33,4.79±0.25,2.98±0.30,模型组分别与低、中、高剂量实验组比较,差异均有统计学意义(均P<0.05)。结论拉莫三嗪对脑外伤大鼠学习记忆能力有修复作用,可能与NF-κB信号通路抑制神经细胞凋亡有关。
Objective To investigate the effects of lamotrigine on spatial learning and memory function and NF-κB signaling pathway in rats with traumatic brain injury.Methods SPF healthy male SD rats were selected,they were randomly assigned to control group,sham-operation group,model group,exp-L group,exp-M group and exp-H group,with 15 rats in each group.The rats in the model group and the exp-L,-M,-H group were hit by Feeney’s free falling brain injury device,while the sham-operation group only underwent skin incision and skull exposure,and the control group was not operated.The exp-L,-M,-H group was given 20,30,60 mg·kg^-1·d^-1 lamotrigine,while the control group,the sham-operation group and the model group received NaCl.The spatial learning and memory function of rats was measured by water maze navigation test after brain injury;Neuronal apoptosis was detected by TUNEL assay;The mRNA expressions of NF-κB,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),cysteine-requiring aspartate protease-1(aspase-1)in brain tissues were detected by quantitative Real-time PCR(qRT-PCR).Results The escape latency of control group,sham operation group,model group and low,medium and high dose experimental group on the 11 th day were(13.16±2.83),(15.53±2.71),(68.21±3.44),(50.06±2.95),(46.31±2.41)and(34.62±2.20)s,respectively;the apoptosis rates were(1.10±0.08)%,(1.21±0.11)%,(4.73±0.34)%,(2.800.22)%,(2.27±0.14)%(1.91±0.20)%;the expression of NF-κB mRNA were 0.82±0.05,1.06±0.08,2.87±0.42,2.01±0.18,1.83±0.12,1.75±0.10;the expression of Bcl-2 mRNA were 1.12±0.17,0.81±0.09,0.23±0.03,0.30±0.05,0.35±0.07,0.67±0.08;the expression of Bax mRNA were 0.96±0.04,1.64±0.23,5.03±0.31,3.77±0.16,2.24±0.08,1.97±0.25;the expression of caspase-1 mRNA were 1.01±0.04,1.75±0.18,8.91±0.36,4.93±0.33,4.79±0.25,2.98±0.30,the difference between model group and exp-L,-M,-H group was statistically significant(all P<0.05).Conclusion Lamotrigine can repair the cognitive function of rats with traumatic brain injury,and it m
作者
王士杰
曹娟
毕见龙
秦宇红
WANG Shi-jie;CAO Juan;BI Jian-long;QIN Yu-hong(Department of Emergency,Peking University International Hospital,Beijing 102206,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2020年第10期1248-1251,共4页
The Chinese Journal of Clinical Pharmacology
