雷公藤多苷对TNBS/乙醇溃疡性结肠炎大鼠脂质过氧化损伤的保护作用  

Protective effect of Tripterygium wilfordii polycoride(TWP) on lipid peroxidation injury in TNBS/ethanol inducing ulcerative colitis(UC) rat

作　　者：周毅骏 钦丹萍[2,3] 杨强 徐晓栋 张春丽 代群[5] 王耀东[3] 

机构地区：[1]杭州市西溪医院,杭州310023 [2]浙江中医药大学附属第一医院消化内科,杭州310006 [3]浙江中医药大学第一临床医学院,杭州310053 [4]浙江中医药大学附属第一医院病理科,杭州310006 [5]浙江中医药大学附属第一医院胃肠研究实验室,杭州310006

出　　处：《中药药理与临床》2017年第5期77-82,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金资助项目(项目批准号:81273903和81673798)

摘　　要：目的:研究雷公藤多苷对2,4,6-三硝基苯磺酸(TNBS)/乙醇溃疡性结肠炎大鼠脂质过氧化损伤的保护作用。方法:通过TNBS联合乙醇灌肠的方法,建立TNBS/乙醇溃疡性结肠炎大鼠模型。造模成功后,90只雄性Wistar大鼠随机分为6组,每组15只,分别为正常对照组、模型对照组、雷公藤多苷3mg/kg、6mg/kg、12mg/kg、硫唑嘌呤6mg/kg,每组各自给予相应药物灌胃治疗,连续14天。每3天进行一次大鼠疾病活动指数(DAI)评分,所有大鼠在14天后均被解剖,相应结肠组织被留取,对各组大鼠结肠组织进行大体及镜下病理评分;同时,进行心脏取血,离心后取上清液,用ELISA法检测血清中MDA、SOD、GSH-Px、IL-1β和TNF-α含量。结果:DAI评分,大体及镜下表现和评分均提示TNBS/乙醇大鼠模型是研究溃疡性结肠炎的极佳模型,雷公藤多苷可显著改善溃疡性结肠炎大鼠临床症状及促进高质量的黏膜愈合,即镜下黏膜愈合,该作用与硫唑嘌呤6mg/kg相当或强于硫唑嘌呤6mg/kg。脂质过氧化反应相关因子ELISA结果提示:与正常对照组相比,模型对照组大鼠体内MDA水平显著升高,SOD、GSH-Px水平显著降低。与模型组相比,雷公藤多苷呈现剂量依赖性地抑制大鼠血清中MDA水平,增加大鼠血清中SOD、GSH-Px水平,其中雷公藤多苷12mg/kg组能显著抑制MDA、促进SOD、GSH-Px释放。同时,硫唑嘌呤6mg/kg的作用略好于雷公藤多苷12mg/kg,但无统计学差异。炎症因子ELISA结果提示雷公藤多苷呈剂量依赖性地抑制血清中IL-1β及TNF-α的表达,其中雷公藤多苷6mg/kg、12mg/kg、硫唑嘌呤6mg/kg与模型对照组相较抑制炎症因子释放更显著;雷公藤多苷12mg/kg与硫唑嘌呤6mg/kg对炎症因子IL-1β及TNF-α的抑制作用相当,但差异无统计学意义。结论:雷公藤多苷可显著减少TNBS/乙醇溃疡性结肠炎大鼠结肠黏膜镜下炎性细胞浸润,最终达到镜下黏膜愈合的目的,其机制之一是通过减少Objectives：To study the protective effect of Tripterygium wilfordii polycoride（TWP）on lipid peroxidation injury in TNBS/ethanol inducing ulcerative colitis（UC）rat.Methods：TNBS and ethanol enema were adopted to build TNBS/ethanol UC rat model.After 90 male Wistar rat models were made,they were divided into 6 groups,including control,model,TWP with 3mg/kg,6 mg/kg,12 mg/kg and azathioprine（AZA）groups,and 15 rats in each group.All rats in each group were administrated by corresponding medicines for 14 days.After14 days administration,corresponding colon tissues were taken to undergo general and microscopic evaluation.Blood samples were taken from hearts and serum was separated by the centrifuge.ELISA was adopted to test levels of MDA,SOD,GSH-Px,IL-1βand TNF-αin serum.Results：DAI,general and microscopic evaluations all showed that TNBS/ethanol UC rat model was successful.TWP improved UC-related clinical manifestation and promoted the colonic mucosa healing procedure and such effect was equal to AZA.ELISA result about lipid peroxidation reaction indicated that compared with the control group,the MDA level was significantly increased,whereas levels of SOD and GSH-Px were significantly decreased（P〈0.01）.Compared with the model group,TWP decreased the MDA level and increased levels of SOD and GSH-Px in a dose-dependent manner.TWP with 12 mg/kg strongly decreased the MDA level and increased levels of SOD and GSH-Px（P〈0.01）.In the meanwhile,AZA also manifested the same effect of TWP and was slightly superior to TWP and difference was no statistical significant（P〉0.05）.ELISA result about inflammatory cytokines indicated that TWP inhibited expressions of IL-1βand TNF-αin a dose-dependent manner in serum,among which TWP with 6mg/kg,12 mg/kg and AZA group significantly inhibited expressions of IL-1βand TNF-αin serum（P〉0.05）.The inhibitory effect against IL-1βand TNF-αbetween TWP with 12mg/kg and AZA group was equal without statistical differences.Conclusion：TWP can significant

关 键 词：雷公藤多苷 溃疡性结肠炎 黏膜愈合 脂质过氧化损伤 

分 类 号：R285.5[医药卫生—中药学]