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摩罗丹浓缩丸治疗慢性萎缩性胃炎的药效及作用机制

Morodan Concentrated Pills for the Treatment of Chronic Atrophic Gastritis and Its Mechanism of Action

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【作者】 殷苗苗睢建亮王梦蕾刘会云刘齐超吴一峰王珍

【Author】 YIN Miaomiao;SUI Jianliang;WANG Menglei;LIU Huiyun;LIU Qichao;WU Yifeng;WANG Zhen;Key Laboratory of Innovative Research on Traditional Chinese Medicine for Stomach Medicine in Hebei Province;Affiliated Hospital of Hebei Engineering University School of Medicine;Handan Pharmaceutical Co.,Ltd.;Biomedical Research Institute of Fudan University;

【通讯作者】 王珍;

【机构】 河北省中成胃药创新研究重点实验室河北工程大学医学院附属医院邯郸制药股份有限公司复旦大学生物医学研究院

【摘要】 目的 探讨摩罗丹浓缩丸对患慢性萎缩性胃炎(chronic atrophic gastritis, CAG)大鼠的治疗效果及可能的作用机制。方法 采用五因素造模法成功建立CAG大鼠模型,随机分成模型组、维酶素组和摩罗丹浓缩丸组,连续给药8 w,正常组和模型组灌胃等体积生理盐水。比较各组大鼠状态和体重变化,记录各组胃液pH,通过HE染色对各组胃组织做病理学评分,并用ELISA试剂盒检测各组胃泌素(GAS-17)、生长抑素(SS)、胃蛋白酶原Ⅰ(PGⅠ)/胃蛋白酶原Ⅱ(PGⅡ)、白介素6(IL-6)和肿瘤坏死因子α(TNF-α)水平。结果 造模16 w后,形成稳定的CAG大鼠模型,与正常组比较,模型组大鼠状态萎靡,体重极显著降低,胃液pH显著上升,萎缩积分显著升高(P<0.01);模型组黏膜层可见少量上皮细胞脱落,固有层底部可见少量的壁细胞数量减少,伴有轻度结缔组织增生,固有层与黏膜下层可见少量淋巴细胞浸润,组织中可见中度出血;AB-PAS染色分析可以看出,黏膜层可见分泌细胞数量明显增多;血清中GAS-17和PGⅠ/PGⅡ均显著降低,而SS、IL-6和TNF-α均显著上升。与模型组相比,维酶素组和摩罗丹浓缩丸组均可显著改善上述指标的变化,但在IL-6和TNF-α水平上,摩罗丹浓缩丸具有更显著的抗炎效果。从HE染色结果可以看出摩罗丹浓缩丸组黏膜层胃上皮结构完整,胃小凹结构清晰,上皮细胞排列紧密,固有层胃腺丰富,主细胞、壁细胞形态结构正常,并且未见明显炎症,维酶素组黏膜层局部可见少量上皮细胞坏死,核碎裂,黏膜下层局部可见明显水肿,结缔组织排列疏松。由此可见,摩罗丹浓缩丸对于改善CAG的效果更优。免疫组化结果显示,给药8 w后,维酶素组和摩罗丹浓缩丸组可使CAG模型大鼠的G、D细胞数量极显著的上升,大鼠胃黏膜萎缩得到好转。结论 摩罗丹浓缩丸可显著减轻CAG大鼠胃萎缩程度,通过调节血清GAS-17、SS、PGⅠ/PGⅡ水平,降低炎症因子IL-6和TNF-α水平,从而起到治疗CAG的作用。

【Abstract】 Objective To explore the therapeutic effect and possible mechanism of Morodan concentrated pills on rats with chronic atrophic gastritis(CAG).Methods The method used a five factor modeling method to successfully establish a CAG rat model, which was randomly divided into a model group, a vitamin enzyme group, and a Morodan concentrated pill group.The drug was continuously administered for 8 weeks, while the normal group and model group were given an equal volume of physiological saline by gavage.Compare the status and weight changes of rats in each group, record the pH of gastric juice in each group, perform pathological scoring on gastric tissue in each group through HE staining, and detect the levels of gastrin(GAS-17),somatostatin(SS),pepsinogen Ⅰ(PG Ⅰ)/pepsinogen Ⅱ(PG Ⅱ),interleukin-6(IL-6),and tumor necrosis factor α(TNF-α) in each group using an ELISA kit.Results After 16 weeks of modeling, a stable CAG rat model was formed.Compared with the normal group, the model group rats showed signs of lethargy, significantly reduced body weight, significantly increased gastric pH,and significantly increased atrophy score(P<0.01);A small amount of epithelial cells can be seen shedding in the mucosal layer of the model group, and a small number of parietal cells can be seen decreasing at the bottom of the lamina propria, accompanied by mild connective tissue proliferation.A small amount of lymphocyte infiltration can be seen in the lamina propria and submucosa, and moderate bleeding can be seen in the tissue; AB-PAS staining analysis showed a significant increase in the number of secretory cells in the mucosal layer; The levels of GAS-17 and PG Ⅰ/PG Ⅱ in serum were significantly reduced, while SS,IL-6,and TNF-α were significantly increased.Compared with the model group, both the vitamin enzyme group and the Morodan concentrated pill group significantly improved the changes in the above indicators.However, at the levels of IL-6 and TNF-α,Morodan concentrated pills have a more significant anti-inflammatory effect.From the HE staining results, it can be seen that the mucosal layer of the Morodan concentrated pill group has a complete gastric epithelial structure, clear gastric pits, tightly arranged epithelial cells, abundant gastric glands in the lamina propria, normal morphology and structure of main cells and parietal cells, and no obvious inflammation.In the vitamin group, a small amount of epithelial cell necrosis and nuclear fragmentation can be seen locally in the mucosal layer, and obvious edema and loose arrangement of connective tissue can be seen locally in the submucosal layer.It can be seen that Morodan concentrated pills have a better effect on improving CAG.The immunohistochemical results showed that after 8 weeks of administration, the vitamin A group and the Morodan concentrated pill group significantly increased the number of G and D cells in the CAG model rats, and improved the atrophy of the gastric mucosa in the rats.Conclusion Morodan Concentrated Pills can significantly alleviate the degree of gastric atrophy in CAG rats, by regulating serum levels of GAS-17,SS,PG Ⅰ/PG Ⅱ,and reducing levels of inflammatory factors IL-6 and TNF-α,thus playing a therapeutic role in CAG.

【基金】 国家自然基金青年项目(32100569);河北省自然科学基金青年项目(C2019402141);河北省高等学校科学技术研究项目(QN2019215);邯郸市科学技术研究与发展计划项目(1727201061,21112093033);河北省生物医药联合基金(H2021402005);河北省重点研发计划项目(21372507D)
  • 【文献出处】 现代中医药 ,Modern Chinese Medicine , 编辑部邮箱 ,2024年02期
  • 【分类号】R285.5
  • 【下载频次】72
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