圣草酚通过调控PPARδ表达对大鼠脑缺血/再灌注损伤的保护作用  

Protective effect of Eriodictyol on cerebral ischemia/reperfusion injury in rats by regulating PPARδexpression

作　　者：李咏 刘立[1] LI Yong;LIU Li(Department of Pharmacy,Wuhan No.4 Hospital,Wuhan 430033,China)

机构地区：[1]武汉市第四医院药学部,武汉430033

出　　处：《中国免疫学杂志》2024年第9期1827-1832,共6页Chinese Journal of Immunology

基　　金：武汉市卫生健康委医学科研项目(WX20B05)。

摘　　要：目的:研究圣草酚预处理对大鼠脑缺血/再灌注(I/R)损伤的保护作用及其作用机制。方法:90只SD大鼠随机分为假手术组、模型组、圣草酚低剂量组(17.5 mg/kg)、圣草酚中剂量组(35 mg/kg)、圣草酚高剂量组(70 mg/kg)和圣草酚高剂量+过氧化物酶体增殖物激活受体δ(PPARδ)拮抗剂GSK3787组(70 mg/kg圣草酚+300μg/kg GSK3787),每组15只。采用双侧颈总动脉夹闭合并低血压法建立大鼠脑I/R模型,造模前使用不同剂量的圣草酚或GSK3787干预大鼠。I/R 24 h后,进行神经功能缺失体征评分;TTC染色观察大鼠脑梗死面积;HE染色观察大脑皮层病理学变化;生化法检测大脑皮层MDA含量及SOD活性;ELISA检测大脑皮层中IL-1β、IL-6及TNF-α水平;Western blot检测大脑皮层中PPARδ、PPARγ辅助活化因子1α(PGC-1α)和NF-κB p65蛋白表达水平。结果:与假手术组比较,模型组大鼠脑组织病理损伤严重,神经功能缺失体征评分、脑梗死面积及大脑皮层中MDA、IL-1β、IL-6和TNF-α含量显著升高(P<0.05),而大脑皮层中SOD活性及PPARδ和PGC-1α表达显著降低(P<0.05),同时NF-κB p65表达显著升高(P<0.05)。与模型组比较,圣草酚各剂量组大鼠脑组织病理损伤减轻,神经功能缺失体征评分、脑梗死面积及大脑皮层中MDA、IL-1β、IL-6和TNF-α含量显著降低(P<0.05),而大脑皮层中SOD活性及PPARδ和PGC-1α表达水平显著升高(P<0.05),NF-κB p65表达水平显著降低(P<0.05)。与圣草酚高剂量组比较,GSK3787联合干预可显著降低圣草酚对大鼠脑I/R损伤的保护作用(P<0.05)。结论:圣草酚预处理对脑I/R损伤具有较好的保护作用,其机制可能与激活PPARδ/PGC-1α信号通路有关。Objective:To study the protective effect of Eriodictyol preconditioning on cerebral ischemia/reperfusion(I/R)injury in rats and its mechanism.Methods:Ninety SD rats were randomly divided into sham operation group,model group,Eriodictyol lowdose group(17.5 mg/kg),Eriodictyol medium-dose group(35 mg/kg),Eriodictyol high-dose group(70 mg/kg)and high-dose group+peroxisome proliferator-activated receptorsδ(PPARδ)antagonist GSK3787 group(70 mg/kg Eriodictyol+300μg/kg GSK3787),with 15 rats in each group.Rat model of cerebral I/R was established by bilateral common carotid artery occlusion combined with hypotension.Before modeling,different doses of Eriodictyol or GSK3787 were used to intervene rats.After 24 hours of I/R,the signs of neurological deficit were scored;the area of cerebral infarction in rats were observed by TTC staining;pathological changes of cerebral cortex was observed by HE staining;content of MDA and activity of SOD in cerebral cortex were detected by biochemical method;levels of IL-1β,IL-6 and TNF-αin cerebral cortex were detected by ELISA;protein expression levels of PPARδ,PPARγcoactivator-1α(PGC-1α)and NF-κB p65 in cerebral cortex were detected by Western blot.Results:Compared with sham operation group,pathological injury of brain tissue was serious,the sign score of neurological deficit,the area of cerebral infarction and contents of MDA,IL-1β,IL-6 and TNF-αin model group were increased significantly(P<0.05),while activity of SOD and protein expression levels of PPARδand PGC-1αwere decreased significantly(P<0.05),meanwhile,protein expression level of NF-κB p65 was increased significantly(P<0.05).Compared with model group,pathological injury of brain tissue was reduced,the sign score of neurological deficit,cerebral infarcition area and contents of MDA,IL-1β,IL-6 and TNF-αin cerebral cortex of rats in different concentrations of Eriodictyol groups were decreased significantly(P<0.05),activity of SOD and protein expression levels of PPARδand PGC-1αwere increased significantly(P<0.

关 键 词：脑缺血/再灌注损伤 圣草酚 过氧化物酶体增殖物激活受体Δ 炎症反应 氧化应激 

分 类 号：R285.5[医药卫生—中药学]