羟基红花黄色素A通过调控环氧合酶2/前列腺素E_(2)信号通路减轻大鼠脑缺血再灌注损伤  

Hydroxylsafflor yellow A alleviating cerebral ischemia-reperfusion injury in rats by regulating cyclooxygenase-2/prostaglandin E2 signaling pathway

作　　者：杨迎春[1] 杨莹 张小良[1] 高赛红[1] 姜庆良 李宇凤 贾书雨 YANG Ying-chun;YANG Ying;ZHANG Xiao-liang;GAO Sai-hong;JIANG Qing-liang;LI Yu-feng;JIA Shu-yu(Department of Anatomy,Fenyang College of Shanxi Medical University,Shanxi Fenyang 032200,China)

机构地区：[1]山西医科大学汾阳学院解剖学教研室,山西汾阳032200

出　　处：《解剖学报》2024年第4期468-474,共7页Acta Anatomica Sinica

基　　金：吕梁市社会发展领域重点研发项目(2022SHFZ24);山西省高等学校科技创新项目(2022L673)。

摘　　要：目的观察羟基红花黄色素A(HSYA)对环氧合酶2(COX-2)/前列腺素E_(2)(PGE_(2))信号通路的影响,探讨HSYA对脑缺血再灌注损伤(CIRI)的保护机制。方法90只雄性SD大鼠随机分为假手术组(S组)、手术组(CIRI组)、HSYA组和塞来昔布组(C组),HSYA组进一步分为HSYA低剂量组(HSYA-L组)、HSYA中剂量组(HSYA-M组)和HSYA高剂量组(HSYA-H组),每组15只。线栓法制备脑缺血再灌注损伤模型。各组大鼠于术前30 min腹腔注射给药,HSYA各组分别给予HSYA 10、15、25 mg/kg,C组给予塞来昔布40 mg/kg,S组和CIRI组给予等量的生理盐水。各组大鼠模型制作苏醒后立刻进行神经功能学评分,再灌注24 h时进行脑梗死体积检测,同时Nissl染色观察神经细胞损伤,Real-time PCR和Western blotting检测COX-2 mRNA和蛋白的变化,ELISA检测PGE_(2)、肿瘤坏死因子α(TNF-α)和白细胞介素(IL)-1β的变化。结果与S组比较,CIRI组神经功能学评分显著升高(P<0.05),脑梗死体积显著增加(P<0.05),神经细胞损伤较重,数目显著降低(P<0.05),COX-2 mRNA和蛋白的表达显著增多,同时PGE_(2)、TNF-α和IL-1β的表达也显著增多(P<0.05);与CIRI组比较,HSYA组及C组神经功能学评分明显降低(P<0.05),脑梗死体积明显减少(P<0.05),神经细胞损伤减轻,数目明显增加(P<0.05),COX-2 mRNA和蛋白及PGE_(2)、TNF-α和IL-1β的表达均明显下降(P<0.05),且HSYA各组之间及HSYA-L组和HSYA-M组与C组比较差异均较显著(P<0.05),而HSYA-H组与C组比较差异无显著性(P>0.05)。结论HSYA减轻缺血性脑卒中再灌注损伤可能与抑制COX-2/PGE_(2)信号通路有关。Objective To observe the effect of hyolroxylsafflor(HSYA)on cyclooxygenase-2(COX-2)/prostaglandin E_(2)(PGE_(2))signaling pathway,and to investigate the protective effect and mechanism of HSYA on cerebral ischemia-reperfusion injury(CIRI).Methods Totally 90 SD male rats were randomly divided into sham-operated group(S group),operation group(CIRI group),HSYA group and celecoxib group(C group),HSYA group subdivided into HSYA low dose group(HSYA-L group),HSYA medium dose group(HSYA-M group)and HSYA high dose group(HSYA-H group),15 rats in each group.CIRI model was prepared by thread embolism method.The rats in each group were given intraperitoneal injection 30 minutes before operation.HSYA groups were given HSYA 10 mg/kg,15 mg/kg,25 mg/kg respectirely;C group was given celecoxib 40 mg/kg;S group and CIRI group were given the same amount of normal saline.Neurofunctional scores of each group of rats were performed immediately after recovery from modeling,cerebral infarction volume was measured 24 hours after reperfusion;At the same time,neuronal injury was observed by Nissl staining,the changes of COX-2 mRNA and protein were detected by Real-time PCR and Western blotting,and the changes of PGE_(2),tumor necrosis factorα(TNF-α)and interleukin(IL)-1βwere detected by ELISA.Results Compared with the S group,in the CIRI group,neurofunctional scores increased dramatically(P<0.05),the volume of cerebral infarction increased dramatically(P<0.05),the damage of neurons increased and the number of neurons decreased dramatically(P<0.05),the expressions of COX-2 mRNA and protein increased dramatically(P<0.05),meanwhile the expressions of PGE_(2),TNF-αand IL-1βwere also found dramatically increased(P<0.05);Compared with the CIRI group,in the HSYA group and C group,neurofunctional scores decreased dramatically(P<0.05),the volume of cerebral infarction was reduced dramatically(P<0.05),the damage of neurons decreased and the number of neurons increased dramatically(P<0.05),the expressions of COX-2 mRNA and protein,PGE_(2),TNF-αa

关 键 词：羟基红花素A 脑缺血再灌注损伤 环氧合酶2/前列腺素E_(2)信号通路 实时定量聚合酶链反应 免疫印迹法 大鼠 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学]