摘要
目的基于转化生长因子-β_(1)(TGF-β_(1))/p38丝裂原活化蛋白激酶(p38MAPK)信号通路探讨祛瘀护膜剂对反流性食管炎(RE)模型大鼠食管黏膜的修复作用机制。方法取60只健康雄性SPF级大鼠,随机选择10只作为正常组,其余大鼠使用“4.2 mm幽门夹+2/3胃底结扎术”建立反流性食管炎大鼠模型,造模7 d后将大鼠随机分为模型组、西药组、祛瘀护膜剂低剂量组、祛瘀护膜剂中剂量组、祛瘀护膜剂高剂量组,每组10只。祛瘀护膜剂各组给予相应剂量祛瘀护膜剂灌胃,西药组给予铝镁加混悬液灌胃,正常组和模型组给予蒸馏水+淀粉灌胃,均连续灌胃14 d。观察灌胃过程中各组大鼠进食情况、行为状态、体重变化及死亡情况,灌胃结束后采用苏木素-伊红(HE)染色观察各组大鼠食管组织病理变化,运用ELISA法检测各组大鼠血清中TGF-β_(1)水平,采用Western blot法检测各组大鼠食管组织中p38MAPK、TGF-β_(1)蛋白表达情况。结果模型组和祛瘀护膜剂高剂量组各死亡1只,其余给药大鼠进食情况、行为状态均明显好于模型组,体重高于模型组。祛瘀护膜剂各组和西药组大鼠食管黏膜下层炎症明显较模型组轻,祛瘀护膜剂高剂量组黏膜上皮基本恢复。模型组大鼠血清TGF-β_(1)水平及食管组织中p38MAPK、TGF-β_(1)蛋白表达量均明显高于正常组(P均<0.05);祛瘀护膜剂各组和西药组血清TGF-β_(1)水平及食管组织中p38MAPK蛋白表达量均明显低于模型组(P均<0.05),且祛瘀护膜剂中、高剂量组均明显低于西药组和祛瘀护膜剂低剂量组(P均<0.05);祛瘀护膜剂各组和西药组食管组织中TGF-β_(1)蛋白表达量均明显高于模型组(P均<0.05),且祛瘀护膜剂低、中、高剂量组依次增高,各组间比较差异均有统计学意义(P均<0.05)。结论祛瘀护膜剂可能通过抑制TGF-β_(1)/p38MAPK信号通路的过度激活,在食管黏膜修复的过程中调控TGF-β_(1)的表达,从而促进大鼠反流性食管炎的黏膜愈合。
Objective It is to explore the mechanism of removing blood stasis and protecting membrane paste on esophageal mucosa repair in rats with reflux esophagitis(RE)based on transforming growth factor-β_(1)(TGF-β_(1))/p38 mitogen activated protein kinase(p38MAPK)signaling pathway.Methods Sixty healthy male SPF rats were selected,in which 10 rats were randomly selected as the normal group,the remaining rats were treated with“4.2 mm pyloric clamp+2/3 gastric fundus ligation”to establish RE rat models.After 7 days of modeling,the rats were randomly divided into model group,western medicine group,low-dose,middle-dose and high-dose groups of removing blood stasis and protecting membrane paste,10 animals in each group.Each group of removing blood stasis and protecting membrane paste was given corresponding dose of removing blood stasis and protecting membrane paste by gavage,the western medicine group was given aluminum-magnesium plus suspension by gavage,and the normal group and model group were given distilled water and starch by gavage,all the groups were continuously treated for 14 days.The changes in eating,behavior,weight and death of the rats in each group were observed during the gavage process.After the treatment,the pathological changes of the esophagus tissue of the rats in each group were observed by hematoxylin-eosin(HE)staining,the level of TGF-β_(1) in rat serum was detected by ELISA method,and the expression of p38MAPK and TGF-β_(1) protein in the esophagus tissue was detected by Western blot.Results One rat died in the model group and the high dose group of removing blood stasis and protecting membrane paste.The eating and behavior of the other rats treated were significantly better than those in the model group,and their body weight was higher than that in the model group.The inflammation of esophageal submucosa in removing blood stasis and protecting membrane paste group and western medicine group was significantly lighter than that in model group,and the mucosal epithelium in high-dose Chinese medicine group basically recovered.The level of serum TGF-β_(1) in the model group and the expression of p38 MAPK and TGF-β_(1) protein in esophageal tissue was significantly higher than that in the normal group(all P<0.05);the level of serum TGF-β_(1) and the expression of p38MAPK protein in esophageal tissue in each group of removing blood stasis and protecting membrane paste and western medicine group were significantly lower than those in the model group(all P<0.05),and the middle and high dose groups were significantly lower than those in the western medicine group and low dose group(all P<0.05);the expression of TGF-β_(1) in esophageal tissue of removing blood stasis and protecting membrane paste group and western medicine group was significantly higher than that in the model group(all P<0.05),and the levels of low,medium and high dose groups were increased in turn,the difference between the groups was statistically significant(all P<0.05).Conclusion Removing blood stasis and protecting membrane paste could regulate TGF-β_(1) in the process of esophageal mucosal repair maybe by inhibiting excessive activation of TGF-β_(1)/p38MAPK signaling pathway,so as to promote the mucosal healing of RE in rats.
作者
黄雪
杨欣
梁国强
徐心怡
朱惠萍
孙宏文
HUANG Xue;YANG Xin;LIANG Guoqiang;XU Xinyi;ZHU Huiping;SUN Hongwen(Nanjing University of Traditional Chinese Medicine,Nanjing 210023,Jiangsu,China;Suzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Traditional Chinese Medicine,Suzhou 215009,Jiangsu,China;Suzhou Science&Technology Town Hospital,Suzhou Jiangsu 215000,Jiangsu,China;Suzhou Academy of Wumen Chinese Medicine,Suzhou Hospital of Traditional Chinese Medicine,Suzhou 215009,Jiangsu,China)
出处
《现代中西医结合杂志》
CAS
2021年第32期3564-3569,共6页
Modern Journal of Integrated Traditional Chinese and Western Medicine
基金
苏州市科技发展计划(民生科技)关键技术项目(SS202082)
苏州市卫健委重点病种诊疗技术项目(LCZX201817)。
关键词
祛瘀护膜剂
大鼠
转化生长因子-β_(1)
P38丝裂原活化蛋白激酶
反流性食管炎
removing blood stasis and protecting membrane paste
rats
transforming growth factorβ_(1)
p38 mitogen activated protein kinase
reflux esophagitis
