BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,...BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,has been shown to significantly improve clinical symptoms in patients with CAG,as demonstrated by a multicenter cohort study(overall effective rate:82.5%,P<0.01).However,the unclear molecular mechanisms and therapeutic targets of AWD limit its international acceptance.AIM To investigate the therapeutic mechanisms of AWD against CAG from an integrated perspective.METHODS In this study,N-methyl-N’-nitro-N-nitrosoguanidine was used to establish a CAG rat model.Serum-derived constituents transferred from AWD were first identified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry.The concentrations of inflammatory cytokines in serum samples were determined by enzyme-linked immunosorbent assay.Moreover,gastric mucosal tissues were analyzed by quantitative realtime polymerase chain reaction to measure messenger RNA(mRNA)levels of the NLRP3 inflammasome.Western blotting was used to detect the protein expression of NLRP3,caspase-1,and interleukin(IL)-1β.To elucidate the regulatory mechanisms underlying AWD treatment,structural alterations of the gut microbiota(GM)and associated metabolites were analyzed using integrated high-throughput sequencing(16S rRNA)and liquid chromatography-mass spectrometry based untargeted metabolomics.This comprehensive approach systematically clarified AWD’s multi-target therapeutic mechanisms against CAG.RESULTS AWD notably reduced serum levels of pro-inflammatory cytokines,such as IL-1β,IL-18,tumor necrosis factor-α,and lipopolysaccharide,demonstrating significant statistical differences(all P<0.01).Additionally,AWD substantially inhibited NLRP3 mRNA expression in gastric mucosal tissue(P<0.01)and concurrently decreased the protein abundance of NLRP3,IL-1β,and caspase-1(all P<0.01),thereby suppressing inflammasome signaling activation.GM analysis indicated that AWD intervention significantly increased the relative abundance of beneficial bacteria.Associated microbial metabolites likely inhibited the NLRP3 inflammasome pathway by modulating immune cell function.Non-targeted metabolomics further indicated that AWD exerted anti-inflammatory effects by regulating critical metabolic pathways,including the Kaposi’s sarcoma-associated herpesvirus infection pathway,autophagy processes,and glycosylphosphatidylinositol-anchor biosynthesis.CONCLUSION AWD alleviates the pathological progression of CAG through multi-target synergistic mechanisms.On one hand,AWD directly suppresses gastric mucosal inflammation by inhibiting NLRP3 inflammasome activation.On the other hand,AWD remodels intestinal microbiota-metabolite homeostasis,enhances intestinal barrier function,and regulates mucosal immune responses.展开更多
Objective: To explore the effects of Anwei decoction (AD) on the protein expression of TFF in rats with chronic atrophic gastritis(CAG). Methods: Forty-eight healthy rats were randomly divided into 4 groups: normal co...Objective: To explore the effects of Anwei decoction (AD) on the protein expression of TFF in rats with chronic atrophic gastritis(CAG). Methods: Forty-eight healthy rats were randomly divided into 4 groups: normal control group, pathologic model group, Anwei Decoction group, and Weifuchun group. CAG was induced in rats with N-methy-N-nitro-N-nitrogua-nidine (MNNG). The protein expression of TFF in rats’ gastric mucosa was determined by immunohistochemistry. Results: Compared with that in the normal control group, the protein expression of TFF1 was significantly enhanced in the pathologic model, Anwei Decoction and Weifuchun groups (both P TFF1 was significantly higher in the Anwei Decoction group than in the Weifuchun group (P < 0.01). Compared with the normal control group, the protein expression of TFF2 was significantly enhanced in the pathologic model, Anwei Decoction and Weifuchun groups (both P < 0.01). The protein expression level of TFF2 was significantly higher in the Anwei Decoction group than in the Weifuchun group (P < 0.01). In comparison with the pathologic model group, the protein expression of TFF3 was remarkably reduced in Anwei Decoction and Weifuchun groups (both P < 0.01). but there was no difference between the group of Anwei decoction and the group of Weifuchun (P > 0.05). Conclusion: Anwei decoction may be effective in the treatment of CAG by enhancing the protein expression of TFF1, TFF2 while reducing that of TFF3 in gastric mucosas.展开更多
目的探讨安胃汤对实验性慢性萎缩性胃炎大鼠模型的TFF1 mRNA表达的影响。方法采用甲基硝基亚硝基胍(MNNG)慢性萎缩性胃炎大鼠模型,48只清洁级健康雄性Wistar大鼠随机分为空白组、病理模型组、安胃汤组、胃复春对照组共4组。光学显微镜...目的探讨安胃汤对实验性慢性萎缩性胃炎大鼠模型的TFF1 mRNA表达的影响。方法采用甲基硝基亚硝基胍(MNNG)慢性萎缩性胃炎大鼠模型,48只清洁级健康雄性Wistar大鼠随机分为空白组、病理模型组、安胃汤组、胃复春对照组共4组。光学显微镜观察胃黏膜病理变化,实时定量PCR方法观察安胃汤对实验性慢性萎缩性胃炎大鼠模型胃黏膜TFF1 mRNA表达的影响。结果安胃汤与胃复春均能改善胃黏膜的病理形态,但以安胃汤效果为佳。与病理模型组相比,安胃汤组和胃复春对照组均显著提高TFF1 mRNA/-βactin相对表达量比值(0.86±0.13 vs 0.54±0.10and 0.83±0.10 vs 0.54±0.10,P<0.01),安胃汤组优于胃复春对照组(0.86±0.13 vs 0.83±0.10,P<0.01)。结论安胃汤能够改善慢性萎缩性胃炎大鼠模型胃黏膜的病理形态,可能通过增加胃黏膜TFF1 mRNA表达而起到治疗CAG作用。展开更多
基金Supported by the National Natural Science Foundation of China,No.81860843Guangxi Administration of Traditional Chinese Medicine Project,No.GZSY23-36 and No.GXZYA20240150。
文摘BACKGROUND Chronic atrophic gastritis(CAG)is a clinically refractory gastric disease often characterized by high recurrence rates and adverse drug reactions.Anwei decoction(AWD),a traditional Chinese medicine formula,has been shown to significantly improve clinical symptoms in patients with CAG,as demonstrated by a multicenter cohort study(overall effective rate:82.5%,P<0.01).However,the unclear molecular mechanisms and therapeutic targets of AWD limit its international acceptance.AIM To investigate the therapeutic mechanisms of AWD against CAG from an integrated perspective.METHODS In this study,N-methyl-N’-nitro-N-nitrosoguanidine was used to establish a CAG rat model.Serum-derived constituents transferred from AWD were first identified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry.The concentrations of inflammatory cytokines in serum samples were determined by enzyme-linked immunosorbent assay.Moreover,gastric mucosal tissues were analyzed by quantitative realtime polymerase chain reaction to measure messenger RNA(mRNA)levels of the NLRP3 inflammasome.Western blotting was used to detect the protein expression of NLRP3,caspase-1,and interleukin(IL)-1β.To elucidate the regulatory mechanisms underlying AWD treatment,structural alterations of the gut microbiota(GM)and associated metabolites were analyzed using integrated high-throughput sequencing(16S rRNA)and liquid chromatography-mass spectrometry based untargeted metabolomics.This comprehensive approach systematically clarified AWD’s multi-target therapeutic mechanisms against CAG.RESULTS AWD notably reduced serum levels of pro-inflammatory cytokines,such as IL-1β,IL-18,tumor necrosis factor-α,and lipopolysaccharide,demonstrating significant statistical differences(all P<0.01).Additionally,AWD substantially inhibited NLRP3 mRNA expression in gastric mucosal tissue(P<0.01)and concurrently decreased the protein abundance of NLRP3,IL-1β,and caspase-1(all P<0.01),thereby suppressing inflammasome signaling activation.GM analysis indicated that AWD intervention significantly increased the relative abundance of beneficial bacteria.Associated microbial metabolites likely inhibited the NLRP3 inflammasome pathway by modulating immune cell function.Non-targeted metabolomics further indicated that AWD exerted anti-inflammatory effects by regulating critical metabolic pathways,including the Kaposi’s sarcoma-associated herpesvirus infection pathway,autophagy processes,and glycosylphosphatidylinositol-anchor biosynthesis.CONCLUSION AWD alleviates the pathological progression of CAG through multi-target synergistic mechanisms.On one hand,AWD directly suppresses gastric mucosal inflammation by inhibiting NLRP3 inflammasome activation.On the other hand,AWD remodels intestinal microbiota-metabolite homeostasis,enhances intestinal barrier function,and regulates mucosal immune responses.
文摘Objective: To explore the effects of Anwei decoction (AD) on the protein expression of TFF in rats with chronic atrophic gastritis(CAG). Methods: Forty-eight healthy rats were randomly divided into 4 groups: normal control group, pathologic model group, Anwei Decoction group, and Weifuchun group. CAG was induced in rats with N-methy-N-nitro-N-nitrogua-nidine (MNNG). The protein expression of TFF in rats’ gastric mucosa was determined by immunohistochemistry. Results: Compared with that in the normal control group, the protein expression of TFF1 was significantly enhanced in the pathologic model, Anwei Decoction and Weifuchun groups (both P TFF1 was significantly higher in the Anwei Decoction group than in the Weifuchun group (P < 0.01). Compared with the normal control group, the protein expression of TFF2 was significantly enhanced in the pathologic model, Anwei Decoction and Weifuchun groups (both P < 0.01). The protein expression level of TFF2 was significantly higher in the Anwei Decoction group than in the Weifuchun group (P < 0.01). In comparison with the pathologic model group, the protein expression of TFF3 was remarkably reduced in Anwei Decoction and Weifuchun groups (both P < 0.01). but there was no difference between the group of Anwei decoction and the group of Weifuchun (P > 0.05). Conclusion: Anwei decoction may be effective in the treatment of CAG by enhancing the protein expression of TFF1, TFF2 while reducing that of TFF3 in gastric mucosas.
文摘目的探讨安胃汤对实验性慢性萎缩性胃炎大鼠模型的TFF1 mRNA表达的影响。方法采用甲基硝基亚硝基胍(MNNG)慢性萎缩性胃炎大鼠模型,48只清洁级健康雄性Wistar大鼠随机分为空白组、病理模型组、安胃汤组、胃复春对照组共4组。光学显微镜观察胃黏膜病理变化,实时定量PCR方法观察安胃汤对实验性慢性萎缩性胃炎大鼠模型胃黏膜TFF1 mRNA表达的影响。结果安胃汤与胃复春均能改善胃黏膜的病理形态,但以安胃汤效果为佳。与病理模型组相比,安胃汤组和胃复春对照组均显著提高TFF1 mRNA/-βactin相对表达量比值(0.86±0.13 vs 0.54±0.10and 0.83±0.10 vs 0.54±0.10,P<0.01),安胃汤组优于胃复春对照组(0.86±0.13 vs 0.83±0.10,P<0.01)。结论安胃汤能够改善慢性萎缩性胃炎大鼠模型胃黏膜的病理形态,可能通过增加胃黏膜TFF1 mRNA表达而起到治疗CAG作用。
