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木瓜三萜对吲哚美辛致胃黏膜损伤小鼠胃酸分泌及胃黏膜屏障的影响
贺海波,张永峰,李小妹,李小琴,覃慧林,刘呈雄,唐红波,汪鋆植,邹坤
1.三峡大学生物与制药学院天然产物研究与利用湖北省重点实验室;2.首都医科大学附属北京妇产医院药剂科
摘要:
观察木瓜三萜对吲哚美辛致胃黏膜损伤小鼠胃酸分泌及胃黏膜屏障的影响,在此基础上探讨其可能的机制。实验时,将小鼠随机分为正常组、模型组、木瓜三萜(50、100mg/kg)和奥美拉唑(20mg/kg)组。将给药组灌胃给予相应的药物,正常组和模型组灌胃给予0.5%羧甲基纤维素钠溶液,给药6小时后,除正常组外,灌胃给予20mg/kg的吲哚美辛,每天一次,连续7天。末次给药次日,小鼠用水合氯醛麻醉后,固定,剪开腹腔,进行胃黏膜血流量的测定,然后取胃检测胃液量、胃液酸度和胃结合黏液量;检测胃黏膜中表皮生长因子基因(EGF)和三叶因子1基因(TFF1)的mRNA和蛋白表达。研究发现:吲哚美辛致胃黏膜损伤模型组小鼠胃液分泌量,胃液酸度、胃黏膜血流量、胃结合黏液量及胃黏膜组织中EGF和TFF1的mRNA和蛋白表达明显降低,与正常组比较均具有统计学差异(P<0.01);用木瓜三萜预处理后,上述异常的变化均得到了有效逆转,与模型组比较具有显著性差异(P<0.05,P<0.01)。实验结果表明木瓜三萜(50、100mg/kg)对吲哚美辛致小鼠胃黏膜损伤具有较好的保护作用,通过上调EGF和TFF1的表达水平,增加胃液分泌量、胃液酸度、胃黏膜血流量、胃结合黏液量,恢复胃黏膜防御屏障的功能可能是其治疗吲哚美辛致胃黏膜损伤的机制之一。
关键词:  木瓜三萜  吲哚美辛  胃黏膜  表皮生长因子  三叶因子1
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Effect of triterpene fromChaenomeles speciosa(Sweet) Nakai on gastric acid secretion and gastric mucosal barrier function in indomethacin induced mice
HE Haibo,ZHANG Yongfeng,LI Xiaomei,LI Xiaoqin,QIN Huilin,LIU Chengxiong,TANG Hongbo,WANG Junzhi,ZOU Kun,Hubei Key Laboratory of Natural Products Research,Development,College of Biological,Pharmaceutical Sciences,China Three Gorges University
Hubei Key Laboratory of Natural Products Research and Development,College of Biological and Pharmaceutical Sciences,China Three Gorges University,Department of Pharmacy,Beijing Obstetrics and Gynecology Hospital Affiliated to Capital Medical University
Abstract:
To investigate the effect of triterpene fromChaenomeles speciosa(Sweet)Nakai on gastric acid secretion and gastric mucosal barrier function in indomethacin induced mice,and to explore its possible mechanism,the mice were randomly divided into normal,model,triterpene fromChaenomeles speciosa(Sweet)Nakai(50and 100mg/kg)and omeprazole(20mg/kg)groups.One time per day,the drug groups were administrated with corresponding drugs,normal and model groups were lavaged with 0.5%sodium carboxymethyl cellulose solution.Every 6hours after intragastric administration,the mice were orally given 20mg/kg indomethacin,1time per day for 7days,except normal group.The day after the last administration,the mice were anesthetized by intraperitoneal injection of chloral hydrate,and the abdominal cavity was cut open and the gastric body was exposed.The gastric mucosal blood flow,gastric mucus content of gastric juice volume,acidity and gastric binding,mRNA and protein expression of epidermal growth factor gene(EGF)and trefoil factor 1 gene(TFF1)in gastric mucosa were determinated.The result showed that in the model mice induced by indomethacin gastric mucosal blood flow,the gastric mucus content of gastric juice volume,acidity and gastric bind-ing,gastric mucosal mRNA and protein expression of EGFand TFF1 were decreased significantly compared with the normal group(P<0.01).After pretreatment with triterpene fromChaenomeles speciosa(Sweet)Nakai,the aforementioned abnormal changes were effectively reversed compared with the model group(P<0.05,P<0.01).Our study displayed that triterpene fromChaenomeles speciosa(Sweet)Nakai(50and 100mg/kg)had a good protective effect on indomethacin induced mice,by upregulating the expression of EGFand TFF1,increasing the gastric mucosal blood flow,gastric mucus content of gastric juice volume,acidity and gastric binding,and then recovering gastric mucosal barrier function.
Key words:  triterpene from Chaenomeles speciosa(Sweet)Nakai  indomethacin  gastric mucosa  epidermal growth factor  trefoil factor 1