有氧运动联合HWTX-Ⅰ调控Ⅱ相解毒酶对阻塞性黄疸致中枢神经系统损伤的影响  

Aerobic exercise combined with huwentoxin-I upregulates phase-Ⅱ detoxification enzymes to alleviate obstructive jaundice-induced central nervous system injury in mice

作　　者：梁微[1] 陈嘉勤[2] 陈伟 LIANG Wei;CHEN Jiaqin;CHEN Wei(Shantou Polytechnic,Shantou 515071,China;Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province,Hunan Normal University,Changsha 410006,China;Hunan Sports Vocational College,Changsha 410019,China)

机构地区：[1]汕头职业技术学院,广东汕头515071 [2]湖南师范大学体适能与运动康复湖南省重点实验室,湖南长沙410006 [3]湖南体育职业学院,湖南长沙410000

出　　处：《南方医科大学学报》2020年第8期1192-1199,共8页Journal of Southern Medical University

基　　金：湖南省教育厅重点项目(1293);动物多肽药物创制国家地方联合工程实验室开放基金课题(2018KF003)。

摘　　要：目的探讨有氧运动联合HWTX-I介导Keap1-Nrf2-ARE途径对II相解毒酶HO-1和NQO1的影响,以及在阻塞性黄疸小鼠中枢神经系统损伤中的保护作用。方法50只雄性KM小鼠随机分为5组,10只/组:空白组(GO),模型组(M),有氧运动组(T),HWTX-I组(H),有氧运动联合HWTX-I组(TH)。M组、T组、H组、TH组小鼠均采用手术线直角悬挂阻断胆总管72 h构建阻塞性黄疸模型。通过有氧运动及尾静脉注射HWTX-I(0.05μg/g)进行干预,采用一般行为学观察及Clark神经功能评分、ELISA酶联免疫、脑组织nissl染色、海马组织Western blot检测、mRNA检测及肝组织mRNA表达谱测序分析,探讨有氧运动及HWTX-I对阻塞性黄疸小鼠脑组织中枢神经损伤的改善效果。结果M组胆总管悬挂72 h后出现明显黄疸症状,皮肤局灶黄染面积增大,尿液变黄及粪便呈浅灰色,Clark神经功能评分显著升高(P<0.01);与M相比,T组、H组、TH组血清肝功能指标ALT、AST、TBIL和TBA含量水平下降(P<0.01),海马组织5-HT、BDNF含量上升,S100B、NSE含量下降(P<0.01),上述除肝功能指标外,有氧运动与HWTX-I间均存在协同效应。镜下显示,M组脑组织皮质神经细胞尼氏小体大量丢失,有明显空泡、深染,大量核固缩、核坏死。T组、H组针对上述症状明显改善,TH组干预效果最佳。相比M组,T组、H组、TH组脑组织中Nrf2、HO-1、NQO1 mRNA表达及蛋白表达水平显著升高(P<0.01,P<0.05),且有氧运动与HWTX-I间均存在协同效应。Illumina高通量测序筛选肝组织神经相关因子及关联分析显示,差异表达因子主要富集于神经活性配体-受体相互作用、GABA能突触、多巴胺能突触、突触小泡循环及轴突指导等神经调控通路,涉及组织细胞神经细胞信号转导、凋亡抑制、免疫反应、毒性等,有氧运动与HWTX-I可显著增加神经元损伤修复、增殖等相关信号通路的富集。且有氧运动与HWTX-I间均存在协同效应。结论7周有氧运动�Objective To explore the effects of aerobic exercise combined with huwentoxin-I(HWTX-I)-mediated Keap1-Nrf2-ARE pathway on phase II detoxification enzymes HO-1 and NQO1 and their protective effects against obstructive jaundice(OJ)-induced central nervous system injury in mice.Methods 50 male KM mice were randomly divided into blank group(GO),model group(M),aerobic exercise group(T),HWTX-I group(H),and aerobic exercise combined with HWTX-I group(TH).Mouse models of OJ were established with surgical suture for 72 h in the mice in all the groups except for the blank control group.The mice received interventions by aerobic exercise and tail vein injection of HWTX-I(0.05μg/g)and were assessed by behavioral observation,Clark's neurological function scores,enzyme-linked immunosorbent assay(ELISA),brain tissue Nissl staining,hippocampal tissue Western blotting,and liver tissue mRNA expression profiling and sequencing.Results The mice in group M had obvious jaundice symptoms after the operation with significantly increased Clark's neurological score(P<0.01).Compared with those in group M,the mice in group T,group H,and group TH showed significantly decreased serum levels of ALT,AST,TBIL,and TBA(P<0.01)with increased contents of 5-HT and BDNF and decreased contents of S100B and NSE in the hippocampus(P<0.01).Synergistic effects between aerobic exercise and HWTX-I were noted on the above parameters except for the liver function indicators.Interventions with aerobic exercise and HWTX-I,alone or in combination,obviously lessened pathologies in the brain tissue induced by OJ,and the combined treatment produced the strongest effect.The treatment also increased the expression levels of Nrf2,HO-1,and NQO1 mRNA and protein in brain tissues(P<0.01 or 0.05)with a synergistic effect between aerobic exercise and HWTX-I.Illumina high-throughput sequencing showed that the differentially expressed factors participated mainly in such neural regulatory pathways as neuroactive ligand-receptor interaction,GABAergic synapses,dopaminergic syn

关 键 词：有氧运动 虎纹蜘蛛毒素 阻塞性黄疸 II相解毒酶 中枢神经系统 

分 类 号：R575[医药卫生—消化系统] R747.9[医药卫生—内科学]