中国免疫学杂志2024，Vol.40Issue(8)：1640-1645,6.DOI:10.3969/j.issn.1000-484X.2024.08.012
水蛭素调节RhoA/ROCK信号通路对脑梗死大鼠神经元细胞凋亡和炎症反应的影响
Impacts of hirudin on neuronal apoptosis and inflammatory response in rats with cerebral infarction by regulating RhoA/ROCK signaling pathway
摘要
Abstract
Objective:To investigate the impacts of hirudin(HRD)on neuronal apoptosis and inflammatory response in rats with cerebral infarction by regulating Ras homolog gene family member A(RhoA)/Rho-associated coiled-coil-forming protein kinase(ROCK)signaling pathway.Methods:SD rats were grouped into Ct group,Model group,low-dose HRD group(HRD-L group,13.33 mg/kg),high-dose HRD group(HRD-H group,26.66 mg/kg),positive control Nimodipine group(NMDP group,40 mg/kg),U-46619(RhoA agonist,0.03 mg/kg)group and HRD-H+U-46619 group(26.66 mg/kg+0.03 mg/kg),with 24 rats per group.Except for the Ct group,rats in other groups constructed the rat model of cerebral infarction by the modified suture method.The rats in the Ct group only exposed the blood vessels without incision and suture insertion.After 1 hour of successful modeling,drug treatment was car-ried out,once a day for 4 weeks.Zea-Longa method was applied to evaluate the neurological function of rats;dry and wet weight meth-od was applied to detect the water content of rat brain tissue;2,3,5-triphenyltetrazolium chloride(TTC)staining was applied to deter-mine the volume of cerebral infarction in rats;TUNEL staining was applied to detect the apoptosis of neurons in the CA1 region of the hippocampus of rats.The levels of TNF-α,IL-1β and IL-6 in rat hippocampus were detected by ELISA;the protein expressions of cleaved-Caspase-3 Cleaved-Caspase-3,Bcl-2-associated X protein(Bax),RhoA,ROCK1 and ROCK2 in rat hippocampus were de-tected by Western blot.Results:Compared with Ct group,the neurological function scores,brain tissue water content,cerebral in-farction volume percentage,neuron apoptosis rate,levels of TNF-α,IL-1β,IL-6,the protein expressions of Cleaved-Caspase-3,Bax,RhoA,ROCK1 and ROCK2 increased in the Model group(P<0.05).Compared with Model group,the neurological function scores,brain tissue water content,cerebral infarction volume percentage,neuron apoptosis rate,levels of TNF-α,IL-1β,IL-6,the protein expressions of Cleaved-Caspase-3,Bax,RhoA,ROCK1 and ROCK2 decreased in HRD-L group,HRD-H group,NMDP group,however,the corresponding index changes in the U-46619 group showed an opposite trend(P<0.05).Compared with HRD-H group,the neurological function scores,brain tissue water content,cerebral infarction volume percentage,neuron apoptosis rate,levels of TNF-α,IL-1β,IL-6,the protein expressions of Cleaved-Caspase-3,Bax,RhoA,ROCK1 and ROCK2 were increased in the HRD-H+U-46619 group(P<0.05).Conclusion:HRD may inhibit neuronal apoptosis and inflammatory response in rats with cerebral infarction by inhibiting RhoA/ROCK signaling pathway.关键词
水蛭素/脑梗死/炎症/Ras同源基因家族成员A/Rho相关卷曲螺旋形成蛋白激酶信号通路/细胞凋亡Key words
Hirudin/Cerebral infarction/Inflammation/Ras homolog gene family member A/Rho-associated coiled-coil-forming protein kinase signaling pathway/Apoptosis分类
医药卫生引用本文复制引用
那丽莎,曲娜,于雪,栗昭生..水蛭素调节RhoA/ROCK信号通路对脑梗死大鼠神经元细胞凋亡和炎症反应的影响[J].中国免疫学杂志,2024,40(8):1640-1645,6.基金项目
黑龙江省中医药科研项目(ZHY2020-181) （ZHY2020-181）
黑龙江省卫生健康委科研课题(2019-416). （2019-416）
