摘要
目的基于Janus激酶2/信号转导与转录激活子3(JAK2/STAT3)通路探讨藏红花素对大鼠局灶性脑缺血再灌注(FCIR)损伤的影响。方法96只SD大鼠随机分为假手术组、模型组、藏红花素(20 mg/kg)组、藏红花素(20 mg/kg)+香豆霉素(JAK2激活剂,0.1 mg/kg)组,每组24只;采用线栓法复制FCIR大鼠模型。造模前7 d开始,各组分别1次/d腹腔注射(ip)给药,假手术组和模型组ip给予生理盐水。再灌注24 h后,通过Longa评分考察大鼠神经功能缺损状况,TTC染色法计算脑梗死率,HE染色、TUNEL染色法观察皮质神经元病理学改变和凋亡状况,ELISA法检测脑组织TNF-α、IL-1β水平,Western blot检测JAK2、p-JAK2、STAT3、p-STAT3、高迁移率族蛋白B1(HMGB1)、Caspase-3、Cleved Caspase-3、B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2相关X蛋白(Bax)表达。结果与模型组相比,藏红花素组大鼠Longa评分和脑梗死率降低(P<0.05);皮质神经元排列紊乱、数量减少、空泡变性、胞浆固缩深染、核膜边界不清、炎细胞浸润等病变明显改善,凋亡指数降低(P<0.05);TNF-α、IL-1β水平降低(P<0.05),pJAK2/JAK2、p-STAT3/STAT3、Cleved Caspase-3/Caspase-3、Bax/Bcl-2表达比值和HMGB1表达量降低(P<0.05)。香豆霉素明显逆转藏红花素对FCIR大鼠上述各指标的调控作用(P<0.05)。结论藏红花素可抑制FCIR大鼠炎症反应和皮质神经元凋亡,对大鼠FCIR损伤起到保护作用,其机制可能与抑制JAK2/STAT3通路活化有关。
Objective To investigate the effects of Crocin on focal cerebral ischemia-reperfusion(FCIR)injury in rats based on janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway.Methods Ninetysix SD rats were randomly divided into sham operation group,model group,Crocin(20 mg/kg)group,crocin(20 mg/kg)+Coumarin(JAK2activator,0.1 mg/kg)group,n=24;the rat model with FCIR was replicated by suture method.7 days before modeling,the drugs were given by intraperitoneal injection(ip)once a day,and the rats in sham operation group and model group were given saline by ip.24 h after reperfution,the neurological deficits were investigated according to Longa scores,cerebral infarction rate was counted through TTC staining method.The pathological changes and apoptosis of cortical neurons were observed by HE staining and TUNEL staining.The level of inflammatory factors(TNF-α,IL-1β)in brain tissue were detected by ELISA method.The expression of JAK2,p-JAK2,STAT3,p-STAT3,high mobility group protein B1(HMGB1),Caspase-3,Cleved Caspase-3,B-lymphoma-2 gene(Bcl-2),Bcl-2-related X protein(Bax)were detected by Western blot.Results Compared with the model group,the Longa score and cerebral infarction rate in Crocin group were decreased(P<0.05);The pathological changes of cortical neurons such as disordered arrangement,decreased number,vacuolar degeneration,hyperchromatic cytoplasmic pyknosis,unclear nuclear membrane boundary,inflammatory cell infiltration were significantly improved,and the apoptosis index was decreased(P<0.05);The level of TNF-α,IL-1βwere decreased(P<0.05);The ratio of p-JAK2/JAK2,p-STAT3/STAT3,Caspase-3/Caspase-3,Bax/Bcl-2 and the expression of HMGB1 were decreased(P<0.05).Coumarin significantly reversed the regulatory effect of Crocin on the above indicators in FCIR rats.Conclusion Crocin can inhibit the inflammatory response and apoptosis of cortical neurons in FCIR rats,and play a protective effect on FCIR injury in rats,which mechanism may be related to the inhibition of JAK2/STAT3 pathway activation.
作者
麻瑞娟
朱海生
李晓蕾
裴娜娜
高晓东
赵伟光
郭敏
MA Rui-juan;ZHU Hai-sheng;LI Xiao-lei;PEI Nana;GAO Xiao-dong;ZHAO Wei-guang;GUO Min(Department of Neurology,Handan Central Hospital,Handan,Hebei Province 056000,China;Department of Anesthesiology,North China Medical and Health Group Handan General Hospital,Handan,Hebei Province 056000,China)
出处
《解剖学研究》
CAS
2022年第6期577-584,共8页
Anatomy Research
基金
河北省邯郸市科学技术研究与发展计划项目(21422083116)
关键词
藏红花素
局灶性脑缺血再灌注
Janus激酶2/信号转导与转录激活子3通路
炎症
凋亡
Crocin
Focal cerebral ischemia-reperfusion
Janus kinase 2/signal transducer and activator of transcription 3 pathway(JAK2/STAT3)
Inflammation
Apoptosis
作者简介
通讯作者:李晓蕾,E-mail:lfsyxiaoyu@163.com
