吴茱萸碱调节JAK2/STAT3/CyclinD1对缺血性脑卒中大鼠的神经保护作用

The neuroprotective effect of evodiamine on ischemic stroke rats by regulating JAK2/STAT3/Cyclin D1

目的 探讨吴茱萸碱(EVO)调节Janus激酶2(JAK2)/信号转导与转录激活子3(STAT3)/细胞周期蛋白D1(CyclinD1)信号通路对缺血性脑卒中大鼠的神经保护作用。方法 所有大鼠随机分为假手术组及造模组,造模组大鼠通过改良线栓法进行制备缺血性脑卒中大鼠模型,假手术组仅分离,但不插入线栓;将造模组造模成功的大鼠随机分为模型组,EVO低、中和高剂量组(分别为10、20、40 mg/kg EVO)(EVO-L、M、H组),EVO-H+AG490组(40 mg/kg EVO+5 mg/kg AG490)。干预结束后,Zea Longa评分检测神经功能缺损;干湿法测定脑水肿;TCC检测脑梗死体积百分比;TUNEL检测细胞凋亡;尼氏染色检测神经元损伤;Western blot检测JAK2/STAT3/CyclinD1信号通路相关蛋白表达。结果 与假手术组相比,模型组尼氏体染色较浅,数目减少,神经元形态不一,Zea Longa评分、脑水肿、脑梗死体积百分比、神经元凋亡显著增加,p-JAK2/JAK2、p-STAT3/STAT3、CyclinD1表达明显降低(P<0.05);与模型组相比,EVO-L组、EVO-M组、EVO-H组神经元损伤逐渐恢复,Zea Longa评分、脑水肿、脑梗死体积百分比、神经元凋亡显著降低,p-JAK2/JAK2、pSTAT3/STAT3、CyclinD1表达明显增加,呈剂量依赖性(P<0.05);AG490逆转了EVO-H对缺血性脑卒中大鼠的神经保护作用。结论 EVO对缺血性脑卒中大鼠的神经保护作用,可能与JAK2/STAT3/CyclinD1信号通路激活有关。

Objective To investigate the neuroprotective effect of evodiamine(EVO)on ischemic stroke rats by regulating Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)/Cyclin DI signal pathway.Methods All rats were randomly divided into sham operation group and model group,the rats in model group were used to prepare the rat model of ischemic stroke through the improved thread embolism method,the sham operation group only separated,but did not insert thread embolism;the rats in the modeling group were randomly divided into model group,EVO low dose(EVO-L)group(10 mg/kg EVO),EVO meddle dose(EVO-M)group(20 mg/kg EVO),EVO high dose(EVO-H)group(40 mg/kg EVO),and EVO-H+AG490 group(40 mg/kg EVO+5 mg/kg AG490).After the intervention,Zea Longa score was used to detect the neurological deficit;brain edema was measured by dry-wet method;the volume percentage of cerebral infarction was detected by TCC;TUNEL was used to detect apoptosis;neuronal damage was detected by nissl staining;and Western blot was used to detect the expression of JAK2/STAT3/CyclinD1 signal pathway related proteins.Results Compared with the sham operation group,the Nissl bodies in the model group were stained shallowly,the number was reduced,and the morphology of neurons was different,the Zea Longa score,cerebral edema,volume percentage of cerebral infarction and neuronal apoptosis increased obviously,the expression of p-JAK2/JAK2,p-STAT3/STAT3 and CyclinD1 decreased obviously(P<0.05);compared with the model group,the neuronal damage in EVO-L group,EVO-M group and EVO-H group gradually recovered,the Zea Longa score,cerebral edema,volume percentage of cerebral infarction,and neuronal apoptosis reduced obviously,the expression of p-JAK2/JAK2,p-STAT3/STAT3 and CyclinD1 increased obviously,in a dose dependent manner(P<0.05);AG490 reversed the neuroprotective effect of EVO-H on ischemic stroke rats.Conclusion The neuroprotective effect of EVO on ischemic stroke rats may be related to the activation of JAK2/STAT3/CyclinD1 signal pathway.