摘要
目的研究瑞巴派特在NSAID相关小肠黏膜损伤中的保护作用及其相关机制。方法选取21只C57BL/6小鼠,采用随机数字表法将其分为阴性对照组(0.9%氯化钠溶液连续灌胃4 d)、吲哚美辛建模组(20 mg/kg吲哚美辛连续灌胃4 d)和瑞巴派特干预组(20 mg/kg吲哚美辛灌胃4 h后,给予320 mg·kg^(-1)·d^(-1)瑞巴派特灌胃,连续4 d),每组7只。建模结束后,通过大体观察和病理学分析吲哚美辛建模组和瑞巴派特干预组小鼠小肠黏膜损伤情况,采用ELISA法检测小鼠血清IL-6、IL-10、三叶因子3、前列腺素E2和EGF的含量,采用实时荧光定量PCR技术检测小鼠小肠组织中IL-6、IL-10、三叶因子3、环氧合酶2和EGF的mRNA表达水平,采用蛋白质印迹法分析小鼠小肠组织中三叶因子3、环氧合酶2和EGF蛋白质相对表达量。采用Levent检验和独立样本t检验进行统计学分析。结果瑞巴派特干预组小鼠的小肠黏膜损伤大体评分和组织学评分均低于吲哚美辛建模组[(2.80±0.45)分比(4.60±1.14)分、(1.67±0.52)分比(3.00±0.71)分],差异均有统计学意义(t=2.667、3.618,P=0.029、0.006)。吲哚美辛建模组小鼠血清IL-6的含量和小肠组织中IL-6的mRNA表达水平均高于阴性对照组,而血清IL-10的含量低于阴性对照组[(48.83±5.40)ng/L比(40.96±5.92)ng/L、5.23±2.36比1.12±0.56、(168.50±10.57)ng/L比(186.30±7.77)ng/L],差异均有统计学意义(t=2.307、3.372、3.366,P=0.047、0.007、0.012);瑞巴派特组小鼠小肠组织中IL-6的mRNA表达水平低于吲哚美辛建模组(1.74±0.82比5.23±2.36),IL-10的mRNA表达水平高于吲哚美辛建模组(6.44±3.46比1.22±0.83),差异均有统计学意义(t=3.409、3.025,P=0.008、0.014)。吲哚美辛建模组小鼠血清三叶因子3、前列腺素E2和EGF的含量,小肠组织中三叶因子3的mRNA表达水平,小肠组织中环氧合酶2和EGF的蛋白质相对表达量均低于阴性对照组[(131.20±16.37)ng/L比(150.30±9.66)ng/L、(32.68±6.88)ng/L
Objective To explore the protective effect and related mechanism of rebamipide on non-steroid anti-inflammatory drug(NSAID)related small intestinal mucosal injury.Methods A total of 21 C57BL/6 mice were selected and by random number table method,they were divided into negative control group(0.9%NaCl gavage for four days),indomethacin modeling group(20 mg/kg indomethacin gavage for four days)and rebamipide intervention group(20 mg/kg indomethacin gavage for four hours and then 320 mg·kg^(-1)·d^(-1)rebamipide gavage for four days),seven mice in each group.After modeling,the injury of mice intestinal mucosa of indomethacin modeling group and rebamipide intervention group was evaluated by gross observation as well as pathological analysis.The serum levels of interleukin(IL)-6,IL-10,trefoil factor 3(TFF3),prostaglandin E2(PGE2)and epidermal growth factor(EGF)in mice were detected by enzyme-linked immunosorbent assay(ELISA).The expression of IL-6,IL-10,TFF3,cyclooxygenase 2(COX2)and EGF at mRNA level of mice small intestinal tissues were examined by real-time quantitative polymerase chain reaction(qRT-PCR).And the relative expression of TFF3,COX2 and EGF at protein level of mice small intestinal tissues were determined by Western blotting.Levene test and independent sample t test were used for statistical analysis.Results The scores of gross observation and histopathology of mice small intestinal mucosa injury of rebamipide intervention group were both lower than those of indomethacin modeling group(2.80±0.45 vs.4.60±1.14,1.67±0.52 vs.3.00±0.71),and the differences were statistically significant(t=2.667 and 3.618,P=0.029 and 0.006).The mouse serum level of IL-6 and the expression of IL-6 at mRNA level in intestinal tissues of indomethacin modeling group were both higher than those of the negative control group,however the serum level of IL-10 was lower than that of the negative control group((48.83±5.40)ng/L vs.(40.96±5.92)ng/L,5.23±2.36 vs.1.12±0.56,(168.50±10.57)ng/L vs.(186.30±7.77)ng/L),and the differen
作者
韩涛涛
陈楚岩
王静
李景南
Han Taotao;Chen Chuyan;Wang Jing;Li Jingnan(Department of Gastroenterology,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China)
出处
《中华消化杂志》
CAS
CSCD
北大核心
2021年第3期183-189,共7页
Chinese Journal of Digestion
基金
国家自然科学基金(81770559)。
