中药药理与临床2025，Vol.41Issue(4)：2-9,8.
理中汤干预MAPK通路治疗脾胃虚寒型胃溃疡大鼠的机制研究
Pharmacodynamic Mechanism of Lizhong(理中)Decoction in Treatment of Gastric Ulcer Due to Piweixuhan(脾胃虚寒)in Rats via MAPK Signaling Pathway
摘要
Abstract
Objective:To investigate the pharmacodynamic effect and molecular mechanism of Lizhong(理中)Decoction(LZD)in the treatment of gastric ulcer(GU)due to Piweixuhan(脾胃虚寒)in rats via the mitogen-activated protein kinase(MAPK)pathway.Methods:Sixty male SD rats were assigned into normal,model,esomeprazole(ESO,4 mg/kg),and LZD(3.75 g/kg and 7.5 g/kg)groups.In 15 days,the rat model of GU due to Piweixuhan was established by the Kuhanxiexia(苦寒泻下)+imbalanced diet+overwork+indomethacin method.The overall state and the nasolabial,tongue,and paw toe conditions of rats were observed.The ulcer index(UI)and curative index(CI)was as-sessed.Hematoxylin-eosin staining was used to reveal and score the pathological changes of the gastric mucosa.The enzyme-linked immu-nosorbent assay was used to measure the levels of interleukin-17(IL-17),tumor necrosis factor-α(TNF-α),malondialdehyde(MDA),and reduced glutathione(GSH)in the serum and the activity of pepsin in the gastric tissue.The protein and mRNA levels of MAPK15,P38 MAPK,matrix metalloproteinase 3(MMP3),and cysteinyl aspartate-specific proteinase 3(CASP3)in the MAPK signaling pathway in the gastric tissue were determined by immunofluorescence assay and droplet digital PCR,respectively.Results:LZD improved the gastric mucosa in the GU rats with Piweixuhan syndrome.Compared with the normal group,the model group showed increased UI(P<0.01),serious edema,detachment,and extensive inflammatory infiltration of epithelium cells(P<0.01),elevated levels of IL-17,TNF-α,and MDA,increased activ-ity of pepsin(P<0.01),decreased GSH content(P<0.01),up-regulated protein and mRNA levels of MAPK15,p38 MAPK,and MMP3(P<0.01),and down-regulated protein and mRNA levels of CASP3(P<0.01).Compared with the model group,LZD decreased UI(P<0.05),and the CI reached 86.95%in the LZD 7.5 g/kg group.Furthermore,LZD decreased the pathological score(P<0.05),lowered the serum levels of IL-17,TNF-α,and MDA,weakened the activity of pepsin(P<0.01),increased the GSH content(P<0.01),down-regulated the protein and mRNA levels of MAPK15,p38 MAPK,and MMP3(P<0.01),and up-regulated the protein and mRNA levels of CASP3(P<0.01).Conclusion:LZD demonstrates a definite effect on GU in the rats with Piweixuhan syndrome as well as the ability to heal ulcers.It may exert the therapeutic effect by regulating the MAPK signaling pathway,inhibiting oxidative stress,reducing inflammation,and promoting gastric mucosal repair.关键词
理中汤/胃溃疡/脾胃虚寒证/炎症反应/氧化应激/丝裂原活化蛋白激酶/基质金属蛋白酶 3/半胱氨酸-天冬氨酸蛋白酶3Key words
Lizhong(理中)Decoction/Gastric ulcer/Piweixuhan(脾胃虚寒)syndrome/Inflammatory response/Oxidative stress/Mitogen-activated protein kinase/Matrix metalloproteinase 3(MMP3)/Cysteinyl aspartate-specific protease 3(CASP3)引用本文复制引用
仇婧玥,宋厚盼,喻昶,熊萌,任保平,仲美琪,周顺华,王晓娟,高晴,曾梅艳..理中汤干预MAPK通路治疗脾胃虚寒型胃溃疡大鼠的机制研究[J].中药药理与临床,2025,41(4):2-9,8.基金项目
国家自然科学基金面上项目(编号:82374429) （编号:82374429）
湖湘青年科技创新人才项目(编号:2021RC3101) （编号:2021RC3101）
湖南省自然科学基金面上项目(编号:2023JJ30460) （编号:2023JJ30460）
"刘良院士工作站"指导项目(编号:22YS003). （编号:22YS003）
