紫檀芪通过COX-2/PGD_(2)/DP_(S)通路减轻脑缺血/再灌注损伤大鼠的神经炎症  

Pterostilbene alleviates the neuroinflammation of cerebral ischemia/reperfusioninjury in rats by regulating COX-2/PGD_(2)/DP_(S) pathway

作　　者：杨迎春[1] 张小良[1] 高赛红[1] 贾书雨 王金瑞 魏己博 王喜悦 YANG Yingchun;ZHANG Xiaoliang;GAO Saihong;JIA Shuyu;WANG Jinrui;WEI Jibo;WANG Xiyue(Department of Anatomy,Fenyang College of Shanxi Medical University,Fenyang 032200,China)

机构地区：[1]山西医科大学汾阳学院解剖学教研室,汾阳032200

出　　处：《神经解剖学杂志》2024年第6期761-767,共7页Chinese Journal of Neuroanatomy

基　　金：吕梁市社会发展领域重点研发项目(2022SHFZ24)。

摘　　要：目的:探讨紫檀芪(PTE)防治大鼠脑缺血再灌注损伤(CIRI)后神经炎症的作用机制。方法:90只雄性SD大鼠随机分为假手术组(sham)、模型组(MCAO/R)、PTE低剂量组(PTE-L)、PTE中剂量组(PTE-M)、PTE高剂量组(PTE-H)。阻塞大脑中动脉(MCAO/R)制备大鼠CIRI模型,Zea Longa评分法评估大鼠神经功能缺损,TTC染色检测脑梗死体积变化,HE染色观察缺血区皮质的形态变化,RT-qPCR及Western Blot检测环氧合酶-2(COX-2)、前列腺素D_(2)受体(DP_(2))、前列腺素D_(1)受体(DP_(1))的表达,ELISA检测前列腺素D_(2)(PGD_(2))、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)的表达。结果:与sham组比较,MCAO/R组神经功能评分显著升高(P<0.05),脑梗死体积显著增加(P<0.05),缺血区皮质损伤加重,COX-2、DP_(2) mRNA和蛋白的表达显著增加(P<0.05),PGD_(2)、IL-1β和TNF-α的表达显著升高(P<0.05);与MCAO/R组比较,PTE-L组、PTE-M组及PTE-H组神经功能评分显著下降(P<0.05),脑梗死体积显著缩小(P<0.05),缺血区皮质损伤明显减轻,COX-2、DP_(2) mRNA和蛋白的表达显著减少(P<0.05),PGD_(2)、IL-1β和TNF-α的表达显著下降(P<0.05),且PTE对脑组织的保护作用呈现量效关系(P<0.05);而各组之间DP_(1) mRNA和蛋白的表达变化无显著性差异(P>0.05)。结论:PTE可通过抑制COX-2/PGD_(2)/DP_(2)信号通路减轻CIRI大鼠的神经炎症。Objective:To explore the mechanism of pterostilbene(PTE)in preventing and treating neuroinflammation after cerebral ischemia-reperfusion injury(CIRI)in rats.Methods:Ninety male SD rats were randomly divided into a sham group,a model group(MCAO/R),a low-dose PTE group(PTE-L),a medium-dose PTE group(PTE-M),and a high-dose PTE group(PTE-H).CIRI model was prepared by middle cerebral artery occlusion reperfusion(MCAO/R)in rats.The neurological deficit in rats was evaluated by Zea Longa score.The volume of cerebral infarction was detected by TTC staining.The morphological changes of ischemic cortex was observed HE staining.The expressions of cyclooxygenase-2(COX-2),prostaglandin D2 receptor(DP_(2))and prostaglandin D1 receptor(DP_(1))were detected by RT-qPCR and Western Blot.The expressions of prostaglandin D2(PGD_(2)),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)were detected by ELISA.Results:Compared with the sham group,the MCAO/R group showed a significant increase in neurological scores(P<0.05),a significant increase in cerebral infarction volume(P<0.05),and aggravated cortical damage in the ischemic area.Additionally,there were significant increase in the expressions of COX-2,DP_(2) mRNA and protein(P<0.05),along with increased expressions of PGD_(2),IL-1βand TNF-α(P<0.05).Compared with the MCAO/R group,the PTE-L,PTE-M,and PTE-H groups showed a significant decrease in neurological scores(P<0.05),a significant decrease in cerebral infarction volume(P<0.05),and markedly alleviated cortical damage in the ischemic region.Additionally,there were significant decrease in the expressions of COX-2,DP_(2) mRNA and protein(P<0.05),along with decreased expressions of PGD_(2),IL-1βand TNF-α(P<0.05).Furthermore,a dose-effect relationship was observed for the neuroprotective effects of PTE on brain tissue(P<0.05).However,there were no significant differences in the expressions of DP_(1) mRNA and protein among all groups(P>0.05).Conclusion:PTE can attenuate the neuroinflammation of CIRI in rats by inhibiting COX

关 键 词：脑缺血/再灌注损伤 紫檀芪 COX-2/PGD_(2)/DP通路 神经炎症 大鼠 

分 类 号：R285.5[医药卫生—中药学]