Objective： To study the effects of Weipixiao （胃痞消, WPX） on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions （GPL）. Methods： Sprague Dawley rats w...Objective： To study the effects of Weipixiao （胃痞消, WPX） on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions （GPL）. Methods： Sprague Dawley rats were randomly divided into control, model, vitacoenzyme （0.2 g·kg-l·day-1）, WPX high-dose （H-WPX, 15 g·kg-l·day-1）, WPX medium-dose （M-WPX, 7.5 g·kg-1·day-1） and WPX low-dose （L-WPX, 3.75 g·kg-l·day-1） groups. After successfully establishing the GPL model, the rats were consecutively administered WPX or vitacoenzyme by gastrogavage for 10 weeks. Differential expression of Leucine-rich repeat-containing G-protein- coupled receptor 5 （Lgr5）, matrix metalloproteinase-7 （MMP-7）, Wntl, Wnt3a, and 13 -catenin in gastric mucosal epithelial cells in all groups were immunohistochemically detected, and the images were taken and analyzed semiquantitatively by image pro plus 6.0 software. Results： Gastric epithelium in the model group showed significantly higher expression levels of Lgr5, MMP-7, Wntl, Wnt3a and 13 -catenin than those of the control group （P〈0.01）. Interestingly, we also observed Lgr5＋ cells, which generally located at the base of the gastric glandular unit, migrated to the luminal side of gastric epithelium with GPL. The expression levels of Lgr5, MMP-7, Wntl, and 13-catenin were all down-regulated in the L-WPX group as compared with those of both model and vitacoenzyme groups （P〈0.05）. A similar, but nonsignificant down-regulation in expression level of Wnt3a was noted in all WPX groups （P〉0.05）. Conclusion： Our findings suggested that the therapeutic mechanisms of WPX in treating GPL might be related with its inhibitory effects on the expressions of Lgr5, MMP-7, Wntl, β -catenin and the aberrant activation of Wnt/β -catenin pathway.展开更多
OBJECTIVE: To investigate the mechanism underlying the action of Weipixiao(WPX) in a rat's model with ameliorating gastric precancerous lesions(GPL).METHODS: HPLC analysis was performed to identify the chemical co...OBJECTIVE: To investigate the mechanism underlying the action of Weipixiao(WPX) in a rat's model with ameliorating gastric precancerous lesions(GPL).METHODS: HPLC analysis was performed to identify the chemical constituents of WPX preparation.Sprague-Dawley rats were randomly assigned into control group, model group, vitacoenzyme group,high-dose WPX group(H-WPX), medium-dose WPX group(M-WPX) and low-dose WPX group(L-WPX).After modeling, the treated rats were administrated WPX or vitacoenzyme intragastrically for consecutive 10 weeks. Gene and protein expressions ofGSK3β, C-myc, Cylin E were evaluated by quantitative real-time reverse transcription-polymerase chain reaction(RT-qPCR) and immunohistochemistry, respectively.RESULTS: WPX could efficiently attenuate the pathological alterations of "non-progressive GPL" in rats.As expected, mRNA and protein levels of C-myc and Cylin E were up-regulated in model rats, while GSK3β expression down-regulated(P < 0.01). WPX treatment, especially at low dose, could significantly down-regulate the m RNA as well as protein levels of C-myc, and could lead to remarkable up-regulation of mRNA and protein levels of GSK3β in GPL rats(P < 0.05). However, no significant changes were observed in WPX-treated rats.CONCLUSION: Our findings suggested that WPX-mediated attenuation of GPL pathological alterations might be due to its regulatory effect on the expressions of GSK3β and C-myc, and on the dysregulation of Wnt/GSK3β pathway.展开更多
基金Supported by the National Natural Science Foundation of China(No.81273739)
文摘Objective： To study the effects of Weipixiao （胃痞消, WPX） on Wnt pathway-associated proteins in gastric mucosal epithelial cells from rats with gastric precancerous lesions （GPL）. Methods： Sprague Dawley rats were randomly divided into control, model, vitacoenzyme （0.2 g·kg-l·day-1）, WPX high-dose （H-WPX, 15 g·kg-l·day-1）, WPX medium-dose （M-WPX, 7.5 g·kg-1·day-1） and WPX low-dose （L-WPX, 3.75 g·kg-l·day-1） groups. After successfully establishing the GPL model, the rats were consecutively administered WPX or vitacoenzyme by gastrogavage for 10 weeks. Differential expression of Leucine-rich repeat-containing G-protein- coupled receptor 5 （Lgr5）, matrix metalloproteinase-7 （MMP-7）, Wntl, Wnt3a, and 13 -catenin in gastric mucosal epithelial cells in all groups were immunohistochemically detected, and the images were taken and analyzed semiquantitatively by image pro plus 6.0 software. Results： Gastric epithelium in the model group showed significantly higher expression levels of Lgr5, MMP-7, Wntl, Wnt3a and 13 -catenin than those of the control group （P〈0.01）. Interestingly, we also observed Lgr5＋ cells, which generally located at the base of the gastric glandular unit, migrated to the luminal side of gastric epithelium with GPL. The expression levels of Lgr5, MMP-7, Wntl, and 13-catenin were all down-regulated in the L-WPX group as compared with those of both model and vitacoenzyme groups （P〈0.05）. A similar, but nonsignificant down-regulation in expression level of Wnt3a was noted in all WPX groups （P〉0.05）. Conclusion： Our findings suggested that the therapeutic mechanisms of WPX in treating GPL might be related with its inhibitory effects on the expressions of Lgr5, MMP-7, Wntl, β -catenin and the aberrant activation of Wnt/β -catenin pathway.
基金Supportted by the National Natural Science Foundation of China(No.81804066 No.81273739+1 种基金 No.81473620)the Research Project of Sichuan Provincial Administration of TCM(No.2018QN022)
文摘OBJECTIVE: To investigate the mechanism underlying the action of Weipixiao(WPX) in a rat's model with ameliorating gastric precancerous lesions(GPL).METHODS: HPLC analysis was performed to identify the chemical constituents of WPX preparation.Sprague-Dawley rats were randomly assigned into control group, model group, vitacoenzyme group,high-dose WPX group(H-WPX), medium-dose WPX group(M-WPX) and low-dose WPX group(L-WPX).After modeling, the treated rats were administrated WPX or vitacoenzyme intragastrically for consecutive 10 weeks. Gene and protein expressions ofGSK3β, C-myc, Cylin E were evaluated by quantitative real-time reverse transcription-polymerase chain reaction(RT-qPCR) and immunohistochemistry, respectively.RESULTS: WPX could efficiently attenuate the pathological alterations of "non-progressive GPL" in rats.As expected, mRNA and protein levels of C-myc and Cylin E were up-regulated in model rats, while GSK3β expression down-regulated(P < 0.01). WPX treatment, especially at low dose, could significantly down-regulate the m RNA as well as protein levels of C-myc, and could lead to remarkable up-regulation of mRNA and protein levels of GSK3β in GPL rats(P < 0.05). However, no significant changes were observed in WPX-treated rats.CONCLUSION: Our findings suggested that WPX-mediated attenuation of GPL pathological alterations might be due to its regulatory effect on the expressions of GSK3β and C-myc, and on the dysregulation of Wnt/GSK3β pathway.
