甘草酸二铵通过Wnt/β-连接蛋白信号通路促进重型颅脑损伤大鼠中枢神经再生修复  

Diammonium glycyrrhizinate promotes the regeneration and repair of central nervous system in rats with severe traumatic brain injury by Wnt/β-catenin signaling pathway

作　　者：刘鑫杰 潘宇政[1] 黄宗轩[1] 彭玲玲[1] 韦春珠 韦进新 Liu Xinjie;Pan Yuzheng;Huang Zongxuan;Peng Lingling;Wei Chunzhu;Wei Jinxin(Department of Traditional Chinese Medicine,First Affiliated Hospital of Guangxi Medical University,Nanning 530021,Guangxi Zhuang Autonomous Region,China;Department of Integrated Traditional Chinese and Western Medicine,Guangxi International Zhuang Medical Hospital,Nanning 530201,Guangxi Zhuang Autonomous Region,China)

机构地区：[1]广西医科大学第一附属医院中医科,南宁530021 [2]广西国际壮医医院中西医结合内科,南宁530201

出　　处：《中华危重病急救医学》2019年第12期1451-1456,共6页Chinese Critical Care Medicine

基　　金：国家中医药管理局"十一五"重点专科建设项目(2008-3);广西壮族自治区卫生厅中医药科技专项(GZLC14-29)。

摘　　要：目的从Wnt/β-连接蛋白信号通路探讨甘草酸二铵(DG)对重型颅脑损伤(STBI)大鼠中枢神经再生修复的影响.方法按随机数字表法将72只雄性SD大鼠均分为正常组、STBI模型组、神经节苷脂(GA)治疗组和DG治疗组.采用改良的Feeney自由落体方法建立STBI大鼠模型;正常组不致伤.制模后6 h,GA治疗组和DG治疗组分别经尾静脉注射单唾液酸四己糖神经节苷脂钠注射液或DG注射液各0.78 mL,每日注射1次,连续注射7 d;正常组和STBI模型组则给予等量生理盐水.各组分别于给药后1、3、7 d取6只大鼠进行神经功能缺损评分(NSS);然后取腹主动脉血和脑组织,采用酶联免疫吸附试验(ELISA)检测血清脑源性神经营养因子(BDNF)、神经生长因子(NGF)含量;取海马齿状回颗粒下区(SGZ)组织,行苏木素-伊红(HE)染色后光镜下观察病理学改变;用实时定量反转录-聚合酶链反应(RT-qPCR)检测海马组织Wnt3a、β-连接蛋白、糖原合成酶激酶-3β(GSK-3β)及Axin的mRNA表达.结果①正常组大鼠无神经功能缺损表现,NSS评分为0分.STBI制模后1 d大鼠NSS评分即明显升高,之后随时间延长逐渐下降.加用GA或DG治疗后1 d大鼠NSS评分即显著低于模型大鼠(分:7.33±2.07、6.17±2.23比9.33±1.63,均P<0.01),且随时间延长呈逐渐下降趋势,至7 d时差异仍有统计学意义(分:2.67±0.82、1.00±0.00比6.17±2.23,均P<0.01),而且DG治疗组的NSS评分较GA治疗组降低更为显著.②正常组大鼠海马SGZ细胞层次、结构清晰,排列较为紧密整齐.STBI模型组大鼠SGZ神经细胞和组织于各个时间点均有不同程度的损伤与破坏.加用GA或DG治疗后大鼠神经组织损伤得以改善,并随时间延长逐渐好转,而DG的作用更为明显.③正常组海马组织Wnt3a、β-连接蛋白的mRNA几乎不表达,GSK-3β、Axin的mRNA表达较高,血清中BDNF和NGF含量很少.STBI制模后1 d,大鼠海马组织Wnt3a、β-连接蛋白的mRNA表达量及血清BDNF、NGF含量�Objective To observe the effects of diammonium glycyrrhizinate(DG)on nerve regeneration repair in rats with severe traumatic brain injury(STBI)from the perspective of Wnt/β-catenin signaling pathway.Methods Seventy-two Sprague-Dawle(SD)male rats were randomly divided into normal group,STBI model group,ganglioside(GA)treatment group and DG treatment group.The STBI animal model was reproduced referring to modified Feeney free fall impact model.No injury was made in normal group.Six hours after modeling,monosialotetrahexosylganglioside sodium injection and DG injection were injected via tail vein of rats in GA treatment group and DG treatment group respectively,once a day for 7 days.Normal group and STBI model group were given the same amount of normal saline.Six rats in each group were sacrificed on the 1st,3rd and 7th day after the challenge for neurological severity score(NSS),and then the blood of abdominal aorta was drawn and brain tissue was harvested.The contents of brain-derived neurotrophic factor(BDNF)and nerve growth factor(NGF)in serum were detected by enzyme linked immunosorbent assay(ELISA).The pathological changes of sub-granular zone(SGZ)were observed under light microscope after hematoxylin eosin(HE)staining.Real-time quantitative reverse transcription-polymerase chain reaction(RT-qPCR)was used to detect the mRNA expressions of Wnt3a,β-catenin,glycogen synthetase kinase-3β(GSK-3β)and Axin.Results①There was no neurological deficit in the normal group and NSS was 0.NSS score of rats increased significantly on the first day after modeling,and then decreased gradually over time.NSS of the rats treated with GA and DG were significantly lower than that of the STBI model rats(score:7.33±2.07,6.17±2.23 vs.9.33±1.63,both P<0.01).Though NSS gradually decreased over time,the differences were still statistically significant on the 7th day(score:2.67±0.82,1.00±0.00 vs.6.17±2.23,both P<0.01),and NSS of DG treatment group was significantly lower than that of GA treatment group.②In SGZ of rats,cells w

关 键 词：甘草酸二铵 颅脑损伤 重型 神经再生修复 Wnt/β-连接蛋白信号通路 

分 类 号：R651[医药卫生—外科学]