布比卡因对发育期大鼠认知功能和海马神经元毒性的影响  

Effects of bupivacaine on cognitive function and hippocampal neuronal toxicity in developing rats

作　　者：周娇洁 刘书婷 徐广民[1] ZHOU Jiao-jie;LIU Shu-ting;XU Guang-min(Department of Anesthesiology,Sichuan Academy of Medical Sciences,Sichuan People's Hospital,Chengdu 610072,Sichuan Province,China)

机构地区：[1]四川省医学科学院·四川省人民医院麻醉科,四川成都610072

出　　处：《中国临床药理学杂志》2022年第6期565-569,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的 研究布比卡因(Bupivacaine, BPV)对发育期大鼠认知功能和海马神经元毒性的影响与其调节Kelch样相关蛋白1/核因子2相关因子/血红素加氧酶(Keap1/Nrf2/HO-1)信号通路的关系。方法 选取SPF级雄性SD大鼠27只,用随机数字表法将其分为3组:正常组、布比卡因组、布比卡因+通路抑制剂(鸦胆子苦醇)组,每组9只。正常组大鼠不做任何干预处理;布比卡因组大鼠经股静脉泵注0.5%布比卡因2 mg·kg^(-1)·min^(-1),制备急性布比卡因中毒模型;布比卡因+通路抑制剂组除股静脉泵注布比卡因外,经侧脑室给予鸦胆子苦醇(Brusatol, Bru) 1 mg·kg^(-1),溶解于1%二甲基亚砜(DMSO)中。通过Morris水迷宫实验检测大鼠的逃避潜伏期和大鼠穿越平台象限次数,以辐射热甩尾法测定鼠尾热痛阈(TEL),以噻唑蓝(MTT)法检测大鼠海马神经元细胞活力,以蛋白质印迹(Western blot)法检测各组大鼠Keap1/Nrf2/HO-1信号通路相关蛋白水平。结果 正常组、布比卡因组和布比卡因+通路抑制剂组的大鼠第5天的逃避潜伏期时间分别为(9.03±1.12),(18.69±1.91),(14.37±1.39)s;大鼠穿越平台象限的次数分别为8.96±0.94,4.12±0.97,7.39±1.03;大鼠5 d的鼠尾热痛阈分别为(3.79±0.39),(13.42±1.39),(8.96±0.97)s;海马神经元细胞活力分别为(100.34±6.76)%,(53.49±6.73)%,(73.21±8.79)%;Keap1蛋白表达水平分别为0.39±0.05,0.89±0.11,0.52±0.07,Nrf2蛋白表达水平分别为0.79±0.09,0.35±0.05,0.68±0.08,HO-1蛋白表达水平分别为0.91±0.09,0.41±0.05,0.77±0.09。上述指标,布比卡因+通路抑制剂组与正常组相比,布比卡因组与布比卡因+通路抑制剂组相比,差异均有统计学意义(均P<0.05)。结论 布比卡因对发育期大鼠认知功能和海马神经元毒性的影响可能与其调节Keap1/Nrf2/HO-1信号通路有关。Objective To investigate the effect of bupivacaine on cognitive function and hippocampal neuronal toxicity in developing rats and its relationship with the regulation of Kelch-like ECH-associated protein 1/nuclear factor erythroid-derived 2/heme oxygenase-1(KEAP1/Nrf2/HO-1) signaling pathway.Methods Twenty-seven SPF male SD rats were selected and divided into 3 groups with 9 rats in each group by random number table method,which were normal group,bupivacaine group and bupivacaine+pathway inhibitor (brusatol)group,respectively.The normal group did not receive any intervention.Bupivacaine group was injected with 0.5%bupivacaine 2 mg·kg^(-1)·min;via femoral vein to prepare acute bupivacaine poisoning model.Bupivacaine+pathway inhibitor group was given brusatol 1 mg·kg^(-1)through lateral ventricle,dissolved in 1%DMSO on the basis of bupivacaine group.Morris water maze test was used to detect the escape latency and the number of times of crossing the platform quadrant of rats.Tail heat pain threshold (TEL) was detected by radiative heat flailing method,MTT was used to detect hippocampal neuron activity,Western blot was used to analyze of Keap1/Nrf2/HO-1 signaling pathway related protein levels in each group.Results The latency of escape in normal group,bupivacaine group and bupivacaine+pathway inhibitor group on the 5;day were(9.03±1.12),(18.69±1.91),(14.37±1.39) s;the times of crossing platform quadrant were 8.96±0.94,4.12±0.97 and 7.39±1.03,the tail heat pain thresholds on 5 d were (3.79±0.39),(13.42±1.39),(8.96±0.97) s;the activity of hippocampal neurons were (100.34±6.76)%,(53.49±6.73)%,(73.21±8.79)%,the expression levels of Keap1 were 0.39±0.05,0.89±0.11,0.52±0.07,the expression levels of Nrf2 were 0.79±0.09,0.35±0.05,0.68±0.08,the expression levels of HO-1 were 0.91±0.09,0.41±0.05,0.77±0.09.The above indicators,between normal group and bupivacaine+pathway inhibitor group,between bupivacaine group and bupivacaine+pathway inhibitor group,the differences were statistically significant respe

关 键 词：布比卡因 Kelch样ECH关联蛋白1/核因子2相关因子/血红素加氧酶(Keap1/Nrf2/HO-1)通路 通路抑制剂 海马神经元细胞 

分 类 号：R97[医药卫生—药品]