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基于JAK2/STAT3通路探究中药地黄对缺血性脑卒中后神经元凋亡的作用及机制

To Explore the Effect and Mechanism of Rehmannia on Neuronal Apoptosis after Ischemic Stroke Based on JAK2/STAT3 Pathway
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摘要 目的:探究中药地黄通过Janus激酶2(JAK2)/信号转导及转录激活因子3(STAT3)通路减少缺血性脑卒中后神经元凋亡的作用及相关机制。方法:选取健康SD大鼠40只,并随机均分为假手术组、模型组、地黄组与阳性对照组4组。采用改良线栓法构建大脑中动脉闭塞缺血性脑卒中大鼠模型;模型建立完成后进行相关给药处理。采用Morris水迷宫实验评估大鼠学习记忆能力;采用Zea–Longa评分及氯化三苯基四氮唑(TTC)染色评估大鼠脑损伤情况;采用末端脱氧核苷酸转移酶标记法(TUNEL)染色观察大鼠海马组织;采用Western blot检测大鼠海马区凋亡相关蛋白BAX、抑凋亡相关蛋白Bcl–2、JAK2/STAT3通路蛋白p–JAK2与p–STAT3蛋白表达情况。结果:与模型组大鼠相比,地黄组大鼠的穿台次数增加且逃避潜伏期缩短,同时神经功能缺损评分明显降低(P<0.05),脑组织梗死灶面积显著降低(P<0.05),海马区神经元凋亡水平明显降低(P<0.05),海马组织神经细胞中Bcl–2表达水平明显上升,BAX、p–JAK2与p–STAT3蛋白表达水平显著下降(P<0.05)。结论:中药地黄可改善缺血性卒中大鼠的认知障碍,减轻神经元凋亡情况,其机制可能与调控凋亡相关信号通路JAK2/STAT3有关。 Objective To investigate the effect of Rehmannia on neuronal apoptosis afteRischemic stroke through Janus kinase 2(JAK2)/signal transduceRand activatoRof transcription 3(STAT3)pathway and its related mechanism.Methods A total of 40 healthy SD rats were selected and randomly divided into sham operation group,model group,Rehmannia group and positive control group.The rat model of ischemic stroke with middle cerebral artery occlusion was established by modified thread thrombus method.Afterthe model was established,relevant drug administration was carried out.Morris wateRmaze test was used to evaluate the learning and memory ability of rats.Zea-longa score and triphenyltetrazolium chloride(TTC)staining were used to evaluate the brain injury of rats.The hippocampal tissues of rats were observed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining.The expressions of apoptosis-related protein BAX,apoptosis-related protein Bcl-2,JAK2/STAT3 pathway proteins P-JAK2 and P-STAT3 were detected by Western blot.Results Compared with the model group rats,the Rehmannia group rats could increase the numbeRof transplatform and shorten the escape latency,and the score of nerve function deficit was significantly decreased(P<0.05),the infarct area of brain tissue was significantly decreased(P<0.05),and the level of neuron apoptosis in hippocampus was significantly decreased(P<0.05).The expression level of BCL-2 was increased and the protein expression levels of BAX,p-JAK2 and p-STAT3 in hippocampus nerve cells were significantly decreased(P<0.05).Conclusion The traditional Chinese medicine Rehmannia can improve the cognitive impairment and reduce the neuronal apoptosis in ischemic stroke rats,and its mechanism may be related to the regulation of apoptosis related signaling pathway JAK2/STAT3.
作者 丁西西 朴军颜 DING Xixi;PIAO Junyan(Third Affiliated Hospital of Henan University of Traditional Chinese Medicine,Henan Zhengzhou 450003;The Sixth People's Hospital of Zhengzhou,Henan Zhengzhou 450000)
出处 《深圳中西医结合杂志》 2024年第8期29-32,I0004,共5页 Shenzhen Journal of Integrated Traditional Chinese and Western Medicine
关键词 缺血性卒中 地黄 JAK2/STAT3信号通路 凋亡 Ischemic stroke Rehmannia JAK2/STAT3 signaling pathway Apoptosis
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