白藜芦醇抑制脊髓损伤兔的NLRP3炎症小体活化  

Esveratrol inhibits NLRP3 inflammasome activation in rabbits with spinal cord injury

作　　者：蒋伟宇[1] 胡旭栋[1] 陈云琳[1] 阮超越 许楠健[1] 王扬[1] 徐顶立 张佳铭 李豪杰 马维虎[1] JIANG Weiyu;HU Xudong;CHEN Yunlin;RUAN Chaoyue;XU Nanjian;WANG Yang;XU Dingli;ZHANG Jiaming;LI Haojie;MA Weihu(Spinal Surgery,Ningbo NO.6 Hospital,Ningbo 315040,Zhejiang,China;Zhejiang Chinese Medical University,Hangzhou 310053,Zhejiang,China)

机构地区：[1]宁波市第六医院脊柱外科浙江省宁波市,浙江宁波315040 [2]浙江中医药大学,浙江杭州310053

出　　处：《中国临床药理学与治疗学》2020年第8期850-856,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：浙江省自然科学基金(LY18H060007);宁波市鄞州区农社类科技计划(2017-1-35)。

摘　　要：目的:研究白藜芦醇抑制NLRP3炎症小体活化保护兔脊髓损伤的机制。方法:将50只雄性日本大耳兔随机分成5组:空白对照组(CON组)、脊髓损伤模型组(SCI组)、白藜芦醇低剂量组(RSV(L)组)、白藜芦醇高剂量组(RSV(H)组),甲基强的松龙组(MP组),每组10只。除CON组外的其他4组均制备脊髓损伤模型。每日静脉给药,CON组和SCI组给予等量生理盐水,连续14 d。Tarlov法进行兔神经行为学评分,发色底物法测定脊髓组织MDA含量及SOD和GSH-Px活力,Western blot测定脊髓神经组织NLRP3、Caspase1 p20,IL-1β,Sirt1,NF-κB p65的蛋白表达,HE染色观察脊髓组织病理变化。结果:白藜芦醇增加脊髓损伤兔行为学评分,促进损伤组织的修复,降低脊髓组织MDA含量,增加SOD和GSH-Px活力,下调脊髓组织NF-κB p65的表达,上调Sirt1的表达,抑制炎症小体NLRP3的表达(脊髓组织NLRP3、Caspase1 p20、IL-1β的表达均降低)。结论:白藜芦醇可促进脊髓损伤兔恢复,其作用机制可能通过激活Sirt1、调节NF-κB通路和体内抗氧化水平,进一步抑制NLRP3炎症小体的活化来发挥作用。AIM:To study the mechanism of resveratrol inhibiting NLRP3 inflammasome activation in rabbits with spinal cord injury.METHODS:Fifty male Japanese big ear rabbits were randomly divided into 5 groups:blank control group(CON group),spinal cord injury model group(SCI group),low-dose resveratrol group(RSV(L)group),and resveratrol high-dose group(RSV(H)group),methylprednisolone group(MP group),10 rabbits in each group.Spinal cord injury models were prepared in all four groups except the CON group.All groups received iv administration daily,and the same amount of normal saline was given to the CON group and the SCI group for 14 consecutive days.The Tarlov method was used to evaluate the neurobehavioral score in rabbits.The chromogenic substrate method was used to determine the MDA content and the activity of SOD and GSH-Px in spinal cord tissues.Western blot was used to determine the proteins expression of NLRP3,Caspase1 p20,IL-1β,Sirt1,NF-κB p65 in spinal cord neural tissues,HE staining to observe the pathological changes of spinal cord tissue.RESULTS:Resveratrol increased the behavioral score of spinal cord injury rabbits,promoted the repair of injured tissues,reduced the MDA content,increased the activity of SOD and GSH-Px in spinal cord tissues,down-regulated the expression of NF-κB p65,up-regulated the expression of Sirt1 in spinal cord tissues,and inhibited expression of NLRP3 in inflammasome(reduction in expression of NLRP3,Caspase1 p20,and IL-1βin spinal cord tissues).CONCLUSION:Resveratrol can promote the recovery of spinal cord injury rabbits,and its mechanism may play a role by activating Sirt1,regulating NF-κB pathway and antioxidant level in vivo,and further inhibiting the activation of NLRP3 inflammasome.

关 键 词：白藜芦醇 脊髓损伤 NLRP3炎症小体 氧化系统 沉默信息调节因子1 

分 类 号：R965.2[医药卫生—药理学]