色甘酸二钠对大鼠脑缺血/再灌注损伤的改善作用及其机制  

Improvement effect of sodium cromoglycate on cerebral ischemia/reperfusion injury in rats and its mechanism

作　　者：朱娴 陈薪旭 陈奕斌 黎昌炫 刘杰 王埮[1] ZHU Xian;CHEN Xinxu;CHEN Yibin;LI Changxuan;LIU Jie;WANG Tan(Department of Neurology,First Affiliated Hospital,Hainan Medical College,Haikou 570102,China)

机构地区：[1]海南医学院第一附属医院神经内科,海南海口570102

出　　处：《吉林大学学报（医学版）》2023年第5期1182-1191,共10页Journal of Jilin University：Medicine Edition

基　　金：海南省卫健委卫生健康行业科研项目(21A200211)。

摘　　要：目的:探讨色甘酸二钠(SCG)对缺血性卒中(CIS)大鼠神经功能和认知功能的影响,阐明其作用机制。方法:选取80只雄性SD大鼠,随机选取18只作为假手术组,剩余大鼠采用线栓法构建大鼠脑缺血/再灌注(I/R)损伤模型。将造模成功的45只大鼠随机分为I/R组、I/R+低剂量SCG组和I/R+高剂量SCG组,每组15只。造模后24 h,I/R+低剂量SCG组和I/R+高剂量SCG组大鼠分别腹腔注射20和60 mg·kg^(-1) SCG,连续2周。采用改良的神经功能缺损程度评分(mNSS)法评估各组大鼠神经功能评分,2,3,5-氯化三苯基四氮唑(TTC)染色检测各组大鼠脑梗死面积,Y型迷宫实验检测各组大鼠记忆能力,电生理检测各组大鼠正确反应率、正确反应时间和兴奋性突触后电位(fEPSP)斜率,高尔基染色检测各组大鼠脑组织中海马齿状回区树突棘密度,免疫荧光法检测各组大鼠脑组织中海马齿状回区5-溴脱氧尿嘧啶核苷(BrdU)阳性细胞数和双肾上腺皮质激素(DCX)蛋白表达水平,Western blotting法检测各组大鼠脑组织中脑源性神经营养因子(BDNF)、抗酪氨酸激酶受体B(TrkB)、神经生长因子3(NT-3)和抗酪氨酸激酶受体C(TrkC)蛋白表达水平。结果:与假手术组比较,I/R组大鼠神经功能评分升高(P<0.05),脑梗死区域面积增大(P<0.05),正确反应率降低(P<0.05),正确反应时间增加(P<0.05),fEPSP斜率和树突棘密度降低(P<0.05),脑组织齿状回区BrdU阳性细胞数和DCX蛋白表达水平差异无统计学意义(P>0.05),海马组织中NT-3蛋白表达水平升高(P<0.05),而BNDF、TrkB和TrkC蛋白表达水平差异无统计学意义(P>0.05)。与I/R组比较,I/R+高剂量SCG组大鼠神经功能评分降低(P<0.05),脑梗死面积减少(P<0.05),正确反应率升高(P<0.05),正确反应时间减少(P<0.05),fEPSP斜率和树突棘密度升高(P<0.05),脑组织中海马齿状回区BrdU阳性细胞数和DCX蛋白表达水平明显升高(P<0.05),大鼠海马组织中BDNF、TrkB、NT-3和TrkC蛋白表Objective:To discuss the effect of sodium cromoglycate(SCG)on the neural function and cognitive function in the rats with cerebral ischemic stroke(CIS),and to clarify its mechanism.Methods:A total of 80 male SD rats were selected and 18 were randomly selected as sham operation group.The remaining rats were constructed the cerebral ischemia/reperfusion(I/R)injury models by thread embolization method.The 45 successful modeling rats were randomly divided into I/R group,I/R+low dose of SCG group,and I/R+high dose of SCG group(n=15).At 24 h after modeling,the rats in I/R+low dose of SCG group and I/R+high dose of SCG group were intraperitoneally injected with 20 and 60 mg·kg^(-1) SCG for 2 weeks,respectively.The neurological scores of the rats in various groups were evaluated by modified neurological severity score(mNSS)criterion;the area of cerebral infarction was detected by using 2,3,5-triphenyltetrazolium chloride(TTC)staining;the Y-maze experiment was used to detect the memory abilities of the rats in various groups;electrophysiological measurement was used to analyze the accurate reaction rate,accurate reaction time,and field excitatory postsynaptic potential(fEPSP)slopes of the rats in various groups;Golgi staining was used to detect the morphology of dendritic spines in dentate gyrus of hippocampus in brain tissue of the rats in various groups;immunofluorescence method was used to detect the numbers of 5-bromodeoxyuridine(BrdU)positive cells and the expression levels of doublecortin(DCX)protein in dentate gyrus of hippocampus in brain tissue of the rats in various groups;Western blotting method was used to detect the expression levels of brain-derived neurotrophic factor(BDNF),tyrosine kinase B receptor(TrkB),neurotrophin 3(NT-3),and tyrosine kinase C receptor(TrkC)proteins in brain tissue of the rats in various groups.Results:Compared with sham operation group,the neurological score and the cerebral infarction area of the rats in I/R group were increased(P<0.05),the accurate reaction rate was decreased(P<0.0

关 键 词：色甘酸二钠 卒中 神经新生 脑缺血 再灌注损伤 认知功能 

分 类 号：R364.6[医药卫生—病理学]