[1]孔德胜,韩欢欢,张兴,等.茯苓多糖调节RhoA/ROCK2信号通路对大鼠脑缺血再灌注损伤的影响[J].卒中与神经疾病杂志,2025,32(01):51-59.[doi:10.3969/j.issn.1007-0478.2025.01.009]
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茯苓多糖调节RhoA/ROCK2信号通路对大鼠脑缺血再灌注损伤的影响()
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第32卷
期数:
2025年01期
页码:
51-59
栏目:
脑梗死
出版日期:
2025-02-20

文章信息/Info

文章编号:
1007-0478(2025)01-0051-09
作者:
孔德胜韩欢欢张兴张坤
056001 河北省邯郸市中心医院[孔德胜 张兴 张坤(通信作者)]; 邯郸市第一医院(韩欢欢)
关键词:
茯苓多糖 脑缺血再灌注 Ras同源基因家族成员A/Rho相关卷曲螺旋蛋白激酶2信号通路 炎症 氧化应激 凋亡
分类号:
R743.33
DOI:
10.3969/j.issn.1007-0478.2025.01.009
文献标志码:
A
摘要:
目的 研究茯苓多糖对大鼠脑缺血再灌注损伤(Cerebral ischemia-reperfusion injury,CIRI)的影响,并基于Ras同源基因家族成员A/Rho相关卷曲螺旋蛋白激酶2(Ras homologous gene family member A/Rho-related coiled-coil protein kinase 2,RhoA/ROCK2)信号通路探讨其作用机制。方法 采用阻断大脑中动脉2 h的方法构建CIRI大鼠模型,设假手术组、模型组、茯苓多糖组、茯苓多糖+RhoA抑制剂Rhosin组和茯苓多糖+RhoA激动剂LPA组,每组各24只; 各组分别1次/d连续给药治疗4周后通过Longa评分评价大鼠神经功能,2,3,5-氯化三苯基四氮唑(2,3,5-Triphenyl-2H-tetrazolium chloride,TTC)染色法检测脑梗死体积,失重法检测脑含水量,通过苏木素-伊红(Hematoxylin eosin,HE)、原位末端标记法(TdT-mediated dUTP nick-end labeling,TUNEL)观察大脑皮层病理变化和神经细胞凋亡状况,酶联免疫吸附法(Enzyme linked immunosorbent assay,ELISA)检测大脑皮层炎症因子[肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白细胞介素(Interleukin,IL)-1β,IL-6]、丙二醛(Malondialdehyde,MDA)水平和抗氧化酶[超氧化物歧化酶(Superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(Glutathione peroxidase,GSH-Px)]活性,反转录-聚合酶链式反应(Reverse transcription-polymerase chain reaction,RT-PCR)法、Western blot法检测RhoA/ROCK2信号通路相关mRNA和蛋白表达水平。结果 与模型组比较,茯苓多糖组和茯苓多糖+Rhosin组Longa评分、脑梗死体积、脑含水量显著降低(P<0.05); 大脑皮层病理变化和神经细胞凋亡状况明显改善,凋亡指数(Apoptosis index,AI)显著降低(P<0.05); 大脑皮层TNF-α,IL-1β,IL-6,MDA水平显著降低,SOD,GSH-Px活性显著升高(P<0.05); RhoA,ROCK2、核因子-κB p65(Nuclear factor-κB p65,NF-κB p65)mRNA和蛋白表达水平显著降低,B细胞淋巴瘤-2(B-cell lymphoma-2,Bcl-2)相关X蛋白(Bcl-2 associated X protein,Bax)/Bcl-2、活化型半胱氨酸天冬氨酸蛋白酶-3(Cleaved cysteine aspartic protease-3,Cleaved Caspase-3)/Caspase-3蛋白表达水平比值显著降低(P<0.05)。与茯苓多糖组比较,茯苓多糖+Rhosin对CIRI大鼠神经功能、脑梗死体积、脑含水量、炎症反应、氧化应激及RhoA/ROCK2信号通路相关mRNA和蛋白表达的调控作用显著增强; 茯苓多糖+LPA对CIRI大鼠各指标的调控作用显著减弱。结论 茯苓多糖对大鼠CIRI具有保护作用,其机制可能与下调RhoA/ROCK2信号通路而减轻炎症反应、氧化应激、细胞凋亡有关。

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备注/Memo

备注/Memo:
基金项目:河北省医学科学研究课题计划(20210110)
更新日期/Last Update: 2025-02-20