中国中医药信息杂志2025，Vol.32Issue(7)：81-87,7.DOI:10.19879/j.cnki.1005-5304.202412275
基于PERK/ATF4信号通路探讨益气活血化浊解毒方对脑缺血再灌注损伤大鼠的影响
Exploration on the Effects of Yiqi Huoxue Huazhuo Jiedu Prescription on Cerebral Ischemia Reperfusion Injury in Rats Based on PERK/ATF4 Signaling Pathway
摘要
Abstract
Objective To investigate the mechanism of Yiqi Huoxue Huazhuo Jiedu Prescription in regulating the endoplasmic reticulum stress PERK/ATF4 signaling pathway to improve cerebral ischemia reperfusion injury in rats.Methods A total of 48 male SD rats were randomly divided into sham-operation group,model group,TCM group and edaravone group,with 12 rats in each group.Cerebral ischemia reperfusion injury rat model was prepared using middle cerebral artery occlusion method,and administration 24 hours after modeling.The edaravone group was given intraperitoneal injection of 1.4 mg/mL edaravone injection,TCM group was given 55 g/(kg·d)of Yiqi Huoxue Huazhuo Jiedu Prescription for gavage,while the sham-operation group and model group were given equal volumes of normal saline for gavage,twice a day for 3 consecutive days.The neurological deficit scores of the rats in each group were observed,TTC staining was used to detect the volume of cerebral infarction,HE staining was used to observe the morphology of brain tissue in the ischemia-reperfusion area,immunohistochemistry staining was used to detect the positive expressions of glucose regulated protein 78(GRP78),protein kinase R-like endoplasmic reticulum kinase(PERK)and transcription activator factor(ATF)4 in the ischemia-reperfusion area brain tissue,RT-PCR was used to detect the mRNA expressions of GRP78,PERK and ATF4 in the ischemia-reperfusion area brain tissue,Western blot was used to detect the protein expressions of GRP78,PERK and ATF4 in the ischemia-reperfusion area brain tissue.Results Compared with the sham-operation group,the neurological deficit score of the model group rats increased,the volume of cerebral infarction increased,the number of neurons in the ischemia-reperfusion area decreased,the arrangement was loose,and the nuclei were condensed,the mRNA and protein expressions of GRP78,PERK and ATF4 increased,with statistical significance(P<0.05).Compared with the model group,the neurological deficit score of TCM group and edaravone group decreased,the cerebral infarction volume decreased,the number and arrangement of neurons of the brain tissue in the ischemia reperfusion area increased,and nuclear condensation decreased in rats,the mRNA and protein expressions of GRP78,PERK and ATF4 were all reduced,with statistical significance(P<0.05).There was no statistical significance in various indicators between TCM group and the edaravone group(P>0.05).Conclusion Yiqi Huoxue Huazhuo Jiedu Prescription can improve cerebral ischemia reperfusion injury,and its mechanism may be related to down-regulating the expression of PERK/ATF4 signaling pathway and alleviating endoplasmic reticulum stress.关键词
缺血性脑卒中/脑缺血再灌注损伤/内质网应激/PERK/ATF4信号通路/益气活血化浊解毒方/大鼠Key words
ischemic stroke/cerebral ischaemia reperfusion injury/endoplasmic reticulum stress/PERK/ATF4 signaling pathway/Yiqi Huoxue Huazhuo Jiedu Prescription/rats分类
医药卫生引用本文复制引用
许甜甜,田晔,王仕铎,张佳运,刘启明,张哲,李希,田军彪..基于PERK/ATF4信号通路探讨益气活血化浊解毒方对脑缺血再灌注损伤大鼠的影响[J].中国中医药信息杂志,2025,32(7):81-87,7.基金项目
河北省重点研发计划项目(20377710D) （20377710D）
河北省中医药管理局科研计划重点项目(Z2022008、2021041) （Z2022008、2021041）
河北中医药大学研究生创新资助项目(XCXZZSS2024047) （XCXZZSS2024047）
河北中医学院科研能力提升重点项目(KTZ2019028) （KTZ2019028）
