摘要
目的:研究木瓜总三萜对非甾体抗炎药(NSAIDs)诱导小肠损伤模型大鼠内源性超氧化物歧化酶/谷胱甘肽过氧化物酶1/过氧化氢酶(SOD/GPX1/CAT)抗氧化系统、细胞外信号调节激酶/核因子2相关因子2/血红素氧合酶-1(ERK/Nrf2/HO-1)和线粒体凋亡信号通路的影响。方法:实验大鼠随机分为正常组、模型组、木瓜总三萜(25、50和100mg/kg)组和雷贝拉唑肠溶片100mg/kg组,各组大鼠灌胃给予相应的药物,每天1次,连续1周,末次给药后禁食,次日再次给药1次; 1小时后,除正常组外,其余各组灌胃给予吲哚美辛45mg/kg 1次。24小时后取血,进行血液中SOD、GSH-Px、CAT和MPO、MDA水平检测;取小肠组织进行溃疡指数和组织形态学分析;实时定量PCR检测小肠组织中SOD1、SOD2、SOD3、GPX1、CAT、Bcl-2、Bax、Caspase-3、Caspase-9基因表达; Western blot检测小肠组织中ERK1/2、p-ERK1/2、胞浆Nrf2、胞核Nrf2、Bcl-2和Bax蛋白表达。结果:木瓜总三萜(25、50和100mg/kg)可显著降低吲哚美辛诱导小肠黏膜损伤大鼠小肠溃疡指数、病理学评分,改善小肠黏膜溃疡、黏膜及黏膜下层肿胀和炎性浸润,显著升高血液中内源性抗氧化酶活性,显著上调受损小肠组织中SOD1、SOD2、SOD3、GPX1、CAT和p-ERK1/2、胞核Nrf2、HO-1、Bcl-2表达,显著下调Bax和Caspase-3、Caspase-9表达,且随着剂量的增加,其作用效果更明显。结论:木瓜总三萜对NSAIDs诱导大鼠小肠损伤具有较好的保护作用,调节内源性SOD/GPX1/CAT抗氧化系统功能及ERK/Nrf2/HO-1和线粒体凋亡信号通路可能是其作用机制之一。
Objective:To investigate effect of total triterpenoids of Chaenomeles speciosa(Sweet) Nakai on the endogenous superoxide dismutase/glutathione peroxidase 1/catalase(SOD/GPX1/CAT) antioxidant system,extracellular signal regulated kinase/nuclear factor 2 related factor2/heme oxygenase-1(ERK/Nrf2/HO-1) and mitochondrial apoptosis signaling pathway against small intestinal injury induced by indomethacin in rats.Methods:The experimental rats were randomly divided into normal group,model group,total triterpenoids of Chaenomeles speciosa(Sweet) Nakai group(25,50 and 100 mg/kg) and rabeprazole group(100 mg/kg).The rats in each group were administered intragastrically the corresponding drugs daily,for 7 days,and another administration the next day after fasting.After 1 hour,all the other groups were given indomethacin(45 mg/kg) for 1 time except the normal group.After 24 hours,the serum levels of SOD,GSH-Px,CAT,MPO,MDA were measured.Small intestinal ulcer index and colonic tissue morphology was analyzed.Real-time PCR was applied to detect the mRNA expressions of SOD1,SOD2,SOD3,GPX1,CAT,Bcl-2,Bax,Caspase-3 and Caspase-9.Protein expressions of ERK1/2、p-ERK1/2,cytoplasm Nrf2,nucleus Nrf2,Bcl-2 and Bax in intestinal tissue were detected by western blotting.Results:Total triterpenoids of Chaenomeles speciosa(Sweet) Nakai group(25,50 and 100 mg/kg) could significantly reduce the small intestinal ulcer index and pathological score of rats induced by indomethacin.It improved small intestinal mucosal ulcers,mucosal and submucosal swelling and inflammatory infiltration.It also up-regulated the expressions of SOD1,SOD2,SOD3,GPX1,CAT and p-ERK1/2,Nrf2,HO-1,Bcl-2 and down-regulated the expressions of Bax and Caspase-3 and Caspase-9 in the damaged small intestine,and there was dose-effect relationship between the three total triterpenoids of Chaenomeles speciosa(Sweet) Nakai pretreated groups.Conclusion:Total triterpenoids of Chaenomeles speciosa(Sweet) Nakai had a good protective effect on NSAIDs induced small intestinal injury in r
作者
李小妹
贺君宇
李爽
陈刚
张永峰
李小琴
石孟琼
杨文雁
张继红
Li Xiaomei;He Juny;Li Shuang;Chen Gang;Zhang Yongfeng;Li Xiaoqin;Shi Mengqiong;Yang Wenyan;Zhang Jihong(College of Biological and Pharmaceutical Sciences,China Three Gorges University;Class201618,No.1Senior High School of Yichang;Medical College of China Three Gorges University;Traditional Chinese Medicine Hospital of China Three Gorges University &Yichang Hospital of Traditional Chinese Medicine,Yichang 443002)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2018年第5期55-60,共6页
Pharmacology and Clinics of Chinese Materia Medica
基金
三峡大学硕士学位论文培优基金(No.2017YPY086、2018SSPY140).
