纳洛酮对高胆红素血症新生大鼠Bcl-2/Bax通路及神经功能障碍的影响  

Effects of naloxone on Bcl-2/Bax pathway and neurological dysfunction in neonatal rats with hyperbilirubinemia

作　　者：张素冰[1] 周秀英 宫昌磊 ZHANG Subing;ZHOU Xiuying;GONG Changlei(Department of Anesthesia and Surgery,First Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin,Heilongjiang 150040,China;Department of Internal Medicine,Daowai Branch,Infectious Disease Hospital of Heilongjiang Province,Harbin,Heilongjiang 150519,China)

机构地区：[1]黑龙江中医药大学附属第一医院麻醉手术科,黑龙江哈尔滨150040 [2]黑龙江省传染病防治院道外分院内科,黑龙江哈尔滨150519

出　　处：《中国优生与遗传杂志》2021年第10期1378-1382,共5页Chinese Journal of Birth Health & Heredity

摘　　要：目的探索纳洛酮对高胆红素血症新生大鼠B淋巴细胞瘤-2/Bcl-2相关X蛋白(Bcl-2/Bax)通路及神经功能障碍的影响。方法建立高胆红素血症新生大鼠模型,随机分为模型组、纳洛酮低剂量组、纳洛酮中剂量组、纳洛酮高剂量组、苯巴比妥组,每组12只,另取12只新生大鼠设为对照组,分组处理后,观察大鼠神经行为学并进行评分;以试剂盒检测大鼠脑组织胆红素含量;原位末端标记法(TUNEL)染色检测大鼠脑组织海马区神经细胞凋亡情况;以酶联免疫吸附实验(ELISA)试剂盒测定大鼠血清中枢神经特异性蛋白(S100β)、神经元特异性烯醇化酶(NSE)、肿瘤坏死因子-α(TNF-α)及白细胞介素-6(IL-6)水平;免疫印迹法检测大鼠脑组织Bcl-2/Bax通路相关蛋白表达水平。结果与对照组相比,模型组大鼠神经行为学评分、脑组织Bcl-2表达显著降低(P<0.05),大鼠脑组织胆红素含量、神经细胞凋亡率、血清S100β、NSE、TNF-α及IL-6水平、脑组织Bax表达显著升高(P<0.05)。与模型组相比,纳洛酮低、中、高剂量组及苯巴比妥组大鼠神经行为学评分、脑组织Bcl-2表达升高(P<0.05),大鼠脑组织胆红素含量、神经细胞凋亡率、血清S100β、NSE、TNF-α及IL-6水平、脑组织Bax表达降低(P<0.05)。结论纳洛酮可下调Bax表达,上调Bcl-2表达,抑制炎症,降低神经细胞凋亡,修复神经功能障碍。Objective To explore the effects of naloxone on B-cell lymphoma-2/Bcl-2 associated X protein(Bcl-2/Bax)pathway and neurological dysfunction in neonatal rats with hyperbilirubinemia.Methods Neonatal rats model with hyperbilirubinemia were established and the rats were randomly divided into model group,low-dose naloxone group,middle dose naloxone group,high-dose naloxone group and phenobarbital group,with 12 rats in each group.And 12 newborn rats were set as control group.After grouped and treated,the neurobehavior of rats was observed and scored,the content of bilirubin in brain tissue of rats was detected by kit,TdT-mediated dUTP-biotin nick end labeling assay(TUNEL)staining was used to detect neuronal apoptosis in hippocampus,the levels of serum central nervous system specific protein(S100β),neuron specific enolase(NSE),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected by enzyme-linked immunosorbent assay;and the expression of Bax-2 protein were detected by Western blot.Results Compared with those in the control group,the neurobehavioral score and the expression of Bcl-2 in brain tissue of rats in model group significantly decreased(P<0.05),the content of bilirubin in brain tissue,the apoptosis rate of nerve cells,the levels of serum S100β,NSE,TNF-αand IL-6,and the expression of Bax in brain tissue significantly increased(P<0.05).Compared with those in the model group,the neurobehavioral score and the expression of Bcl-2 in brain tissue of low,medium and high dose naloxone groups and phenobarbital group were higher significantly(P<0.05),the content of bilirubin in brain tissue,the apoptosis rate of nerve cells,the levels of serum S100β,NSE,TNF-αand IL-6,and the expression of Bax in brain tissue decreased significantly(P<0.05).Conclusion Naloxone can down-regulate the expression of Bax,up-regulate the expression of Bcl-2,inhibit inflammation,reduce the apoptosis of nerve cells and repair the neurological dysfunction.

关 键 词：纳洛酮 高胆红素血症 Bcl-2/Bax通路 神经功能障碍 

分 类 号：R722.1[医药卫生—儿科]