首页|基于HIF-1α/GLUT-1通路探讨阴虚胃痛胶囊治疗慢性萎缩性胃炎大鼠作用机制的研究

基于HIF-1α/GLUT-1通路探讨阴虚胃痛胶囊治疗慢性萎缩性胃炎大鼠作用机制的研究

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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。
Study on the mechanism of Yinxu Weitong capsule in the treatment of chronic atrophic gastritis rats based on HIF-1α/GLUT-1 pathway
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.Meth-ods: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,medi-um-dose,high-dose groups were given corresponding doses of liquid gavage;positive drug group was given vita-min 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 expres-sion 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-1α and GLUT-1 were significantly increased(P<0.01),and the protein ex-pression of HK2,PFKM,PKM2,LDHA were significantly increased(P<0.05).After treatment with low,me-dium and high dose Yinxu Weitong capsule,the gastric mucosal glands were recovered,the mRNA contents of HIF-1α and 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.

Yinxu Weitong capsulechronic atrophic gastritishypoxia inducible factor-1αglucose trans-porter-1signal pathway

李丹艳、张晨晨、丁宁、张卫茜、朱泠霏、张声生

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首都医科大学附属北京中医医院消化中心(北京,100010)

北京中医药大学

阴虚胃痛胶囊 慢性萎缩性胃炎 缺氧诱导因子-1α 葡萄糖转运蛋白-1 信号通路

国家中医药局中医传承与创新"百千万"人才工程(岐黄学者)国家中医药领军人才支撑计划国家自然科学基金青年科学基金

国中医药人教函2021203号82004332

2024

中国中西医结合消化杂志
华中科技大学同济医学院,中国中西医结合学会消化系统疾病专业委员会,中华中医药学会脾胃病专业委员会

中国中西医结合消化杂志

CSTPCD
影响因子:1.363
ISSN:1671-038X
年,卷(期):2024.32(6)
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