木犀草素抑制JAK2/STAT3信号通路减轻大鼠脑缺血再灌注损伤作用的研究  

Effects of luteolin on alleviating cerebral ischemia-reperfusion injury in rats by inhibiting the JAK2/STAT3 signaling pathway

作　　者：吕明义[1] 邓淑玲[1] 郭文晏 邱永升[2] 龙晓凤[1] LYU Mingyi;DENG Shuling;GUO Wenyan;QIU Yongsheng;LONG Xiaofeng(ICU of Internal Medicine,Zhongshan Hospital,Dalian University,Dalian 116001,China;Department of Anesthesiology,Children's Hospital Affiliated to Zhengzhou University)

机构地区：[1]大连大学附属中山医院内科ICU,116001 [2]郑州大学附属儿童医院麻醉科

出　　处：《天津医药》2022年第4期363-368,共6页Tianjin Medical Journal

基　　金：河南省医学科技攻关计划项目(182102310440)。

摘　　要：目的观察木犀草素减轻大鼠脑缺血再灌注损伤的作用并探讨其潜在机制。方法SD大鼠按随机数字表法分为假手术组、大脑中动脉栓塞(MCAO)组、木犀草素低剂量组(50 mg/kg)、木犀草素高剂量组(100 mg/kg)及尼莫地平组(15 mg/kg),灌胃给药,共7 d。采用线栓法建立MCAO大鼠模型,比较神经功能损伤评分、脑组织含水量、脑梗死体积,测定各组肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-6、IL-1β、B细胞淋巴瘤因子2(Bcl-2)、Bcl-2相关X蛋白(Bax)、半胱氨酸蛋白酶3(Caspase-3)含量及磷酸化Janus蛋白酪氨酸激酶2(p-JAK2)、磷酸化信号转导及转录激活蛋白3(p-STAT3)蛋白表达等变化情况。结果与假手术组比较,MCAO组大鼠神经功能损伤评分、脑组织含水量、脑梗死体积、脑组织TNF-α、IL-6、IL-1β、Bax、Caspase-3含量及JAK2、STAT3蛋白磷酸化水平均明显增加(P<0.05),而脑组织Bcl-2含量明显降低(P<0.05);与MCAO组比较,木犀草素低、高剂量组及尼莫地平组大鼠神经功能损伤评分、脑组织含水量、脑梗死体积、脑组织TNF-α、IL-6、IL-1β、Bax、Caspase-3含量及JAK2、STAT3蛋白磷酸化水平均明显降低(P<0.05),而脑组织Bcl-2含量明显增加(P<0.05)。结论木犀草素具有减轻大鼠脑缺血再灌注损伤的作用,该作用与抑制JAK2/STAT3信号通路活化,进而减弱炎症反应及减少细胞凋亡有关。ObjectiveTo study the effect of luteolin on alleviating cerebral ischemia reperfusion injury in rats and its potential mechanism.MethodsSD rats were randomly divided into the sham operation group,the middle cerebral artery occlusion(MCAO)group,the low dose luteolin group(50 mg/kg),the high dose luteolin group(100 mg/kg)and the nimodipine group(15 mg/kg).Rats were administered orally for 7 days.MCAO rat model was established by the method of wire bolt.Changes of neurological function injury score,brain tissue water content,cerebral infarct volume,tumor necrosis factorα(TNF-α),interleukin 6(IL-6),interleukin 1β(IL-1β),B-cell lymphoma factor 2(Bcl-2),Bcl-2 associated X protein(Bax)and Caspase-3 contents,and phosphorylated Janus protein tyrosine kinase 2(p-JAK2)and phosphorylated signal transduction and transcriptional activation protein 3(p-STAT3)protein expression were compared between groups.ResultsNeurological function injury score,brain tissue water content,cerebral infarct volume,TNF-α,IL-6,IL-1β,Bax and Caspase-3 contents,and JAK2 and STAT3 protein phosphorylation levels were significantly increased in the MCAO group compared with the sham operation group(P<0.05),while Bcl-2 content was significantly decreased(P<0.05).Compared with the MCAO group,neurological function injury score,brain tissue water content,cerebral infarct volume,TNF-α,IL-6,IL-1β,Bax and Caspase-3 contents,and JAK2 and STAT3 protein phosphorylation levels were significantly decreased in the low and high dose luteolin groups and the nimodipine group(P<0.05),while Bcl-2 content was significantly increased(P<0.05).ConclusionLuteolin can alleviate cerebral ischemia reperfusion injury in rats,which is related to the inhibition of JAK2/STAT3 signaling pathway,thereby reducing inflammatory response and apoptosis.

关 键 词：木犀草素 再灌注损伤 脑缺血 炎症 细胞凋亡 JANUS激酶2 STAT3转录因子 

分 类 号：R285.5[医药卫生—中药学]