摘要
目的:探讨阴虚胃痛胶囊通过调控缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)/葡萄糖转运蛋白-1(glucose transporter-1,GLUT-1)通路治疗慢性萎缩性胃炎(chronic atrophic gastritis,CAG)大鼠的作用机制。方法:采用N-甲基-N’-硝基-N-亚硝基胍(MNNG)自由饮+灌胃,联合饥饱失常法复合因素干预制备CAG模型。成功建模后,随机将建模大鼠分为模型组及低、中、高剂量阴虚胃痛胶囊组和维酶素组,每组均10只。阴虚胃痛胶囊组按照不同剂量分别给予不同浓度的药液灌胃,维酶素组给予维酶素溶液灌胃,正常组和模型组则给予生理盐水灌胃,灌胃体积均为10 mL/kg,给药8周。利用苏木精-伊红染色法观察大鼠胃黏膜病理变化,使用qRT-PCR和Western blot法检测大鼠胃黏膜中HIF-1α、GLUT-1的mRNA和蛋白表达水平,采用Western blot法检测HK2、PFKM、PKM2、LDHA蛋白表达水平。结果:与正常组比较,模型组大鼠胃黏膜腺体明显减少,HIF-1α、GLUT-1mRNA及蛋白表达水平显著升高(P<0.01),HK2、PFKM、PKM2、LDHA蛋白表达水平显著升高(P<0.05)。经低、中、高剂量阴虚胃痛胶囊治疗后,大鼠胃黏膜腺体较前恢复,HIF-1α、GLUT-1mRNA及HIF-1α、GLUT-1、HK2、PKM2蛋白表达水平明显降低(P<0.05,P<0.01,P<0.001);经中、高剂量阴虚胃痛胶囊治疗后,PFKM、LDHA蛋白表达水平明显降低(P<0.01)。结论:阴虚胃痛胶囊可有效改善CAG大鼠胃黏膜病变,其作用机制可能与调控HIF-1α/GLUT-1通路相关。
Objective To investigate the mechanism of Yinxu Weitong capsule on chronic atrophic gastritis(CAG)rats by regulating hypoxia inducible factor-1α(HIF-1α);glucose transporter-1(GLUT-1)pathway.Methods CAG model was established by free drinking and gavage of N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)combined with compound factors intervention of disturbance of appetite and satiety.After successful modeling,rats in the modeling group were randomly divided into model group,Yinxu Weitong capsule low-dose,medium-dose,high-dose groups and vitamin E group,with 10 rats in each group.Yinxu Weitong capsule low-dose,medium-dose,high-dose groups were given corresponding doses of liquid gavage;positive drug group was given vitamin E suspension gavage,normal group and model group were given saline gavage.The gavage volume was 10 mL;kg,and the drug was given for 8 weeks.The pathological changes of gastric mucosa in each group of CAG rats were observed by HE staining.The mRNA and protein expression levels of HIF-1α,GLUT-1 in gastric mucosa of each group of CAG rats were detected by qRT-PCR and Western blot methods,and the protein expression levels of HK2,PFKM,PKM2 and LDHA were detected by Western blot method.Results Compared with the normal group,the gastric mucosal glands of rats in the model group were significantly reduced,the mRNA content and protein expression of HIF-1αand GLUT-1 were significantly increased(P<0.01),and the protein expression of HK2,PFKM,PKM2,LDHA were significantly increased(P<0.05).After treatment with low,medium and high dose Yinxu Weitong capsule,the gastric mucosal glands were recovered,the mRNA contents of HIF-1αand GLUT-1 and the protein expressions of HIF-1α,GLUT-1,HK2 and PKM2(P<0.05,P<0.01,P<0.001)were significantly decreased,and the protein levels of PFKM and LDHA were significantly decreased after treatment with medium and high dose Yinxu Weitong capsule(P<0.01).Conclusion Yinxu Weitong capsule can effectively improve gastric mucosal lesions in CAG rats,and its mechanism may be related to the regulation of HIF-1α;GLUT-1 pathway.
作者
李丹艳
张晨晨
丁宁
张卫茜
朱泠霏
张声生
LI Danyan;ZHANG Chenchen;DING Ning;ZHANG Weixi;ZHU Lingfei;ZHANG Shengsheng(Digestive Disease Center,Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing,100010,China;Beijing University of Chinese Medicine)
出处
《中国中西医结合消化杂志》
CAS
2024年第6期487-492,共6页
Chinese Journal of Integrated Traditional and Western Medicine on Digestion
基金
国家中医药管理局中医传承与创新“百千万”人才工程(岐黄学者)—国家中医药领军人才支撑计划项目[No:国中医药人教函(2021)203号]
国家自然科学基金青年科学基金项目(No:82004332)。
