AIM: To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. METHODS: Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A contr...AIM: To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. METHODS: Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A control group received the vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration. Intestinal permeability was evaluated by Evans blue and the FITC-dextran method. The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM). Mitochondrial function including mitochondrial swelling, mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were measured. Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. RESULTS: Compared with the control group, intestinal permeability was significantly increased in the diclofenac group, which was accompanied by broken tight junctions, and significant increases in MDA content and MPO activity. Rebamipide significantly reduced intestinal permeability, improved inter-cellular tight junctions, and was associated with decreases in intestinal MDA content and MPO activity. At the mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level and decreased mitochondrial swelling. CONCLUSION: Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.展开更多
BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients.However,they can also damage normal cells and cause serious intestinal toxicity,leading to gastrointestina...BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients.However,they can also damage normal cells and cause serious intestinal toxicity,leading to gastrointestinal mucositis[1].Traditional Chinese medicine is effective in improving the side effects of chemotherapy.Wumei pills(WMP)was originally documented in the Treatise on Exogenous Febrile Diseases.It has a significant effect on chronic diarrhea and other gastrointestinal diseases,but it is not clear whether it affects chemotherapy induced intestinal mucositis(CIM).AIM To explore the potential mechanism of WMP in the treatment of CIM through experimental research.METHODS We used an intraperitoneal injection of 5-fluorouracil(5-Fu)to establish a CIM mouse model and an oral gavage of WMP decoction(11325 and 22650 mg/kg)to evaluate the efficacy of WMP in CIM.We evaluated the effect of WMP on CIM by observing the general conditions of the mice(body weight,food intake,spleen weight,diarrhea score,and hematoxylin and eosin stained tissues).The expression of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,and myeloperoxidase(MPO),as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB(TLR4/MyD88/NF-κB)signaling pathway proteins and tight junction proteins(zonula occludens-1,claudin-1,E-cadherin,and mucin-2)was determined.Furthermore,intestinal permeability,intestinal flora,and the levels of short-chain fatty acids(SCFA)were also assessed.RESULTS WMP effectively improved the body weight,spleen weight,food intake,diarrhea score,and inflammatory status of the mice with intestinal mucositis,which preliminarily confirmed the efficacy of WMP in CIM.Further experiments showed that in addition to reducing the levels of TNF-α,IL-1β,IL-6,and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins,WMP also repaired the integrity of the mucosal barrier of mice,regulated the intestinal flora,and increased the levels of SCFA(such as butyric acid).CONCLUSION WMP展开更多
BACKGROUND The intestinal mucosal barrier is the first line of defense against numerous harmful substances,and it contributes to the maintenance of intestinal homeostasis.Recent studies reported that structural and fu...BACKGROUND The intestinal mucosal barrier is the first line of defense against numerous harmful substances,and it contributes to the maintenance of intestinal homeostasis.Recent studies reported that structural and functional changes in the intestinal mucosal barrier were involved in the pathogenesis of several intestinal diseases.However,no study thoroughly evaluated this barrier in patients with functional constipation(FC).AIM To investigate the intestinal mucosal barrier in FC,including the mucus barrier,intercellular junctions,mucosal immunity and gut permeability.METHODS Forty FC patients who fulfilled the Rome IV criteria and 24 healthy controls were recruited in the Department of Gastroenterology of China-Japan Friendship Hospital.The colonic mucus barrier,intercellular junctions in the colonic epithelium,mucosal immune state and gut permeability in FC patients were comprehensively examined.Goblet cells were stained with Alcian Blue/Periodic acid Schiff(AB/PAS)and counted.The ultrastructure of intercellular junctional complexes was observed under an electron microscope.Occludin and zonula occludens-1(ZO-1)in the colonic mucosa were located and quantified using immunohistochemistry and quantitative real-time polymerase chain reaction.Colonic CD3+intraepithelial lymphocytes(IELs)and CD3+lymphocytes in the lamina propria were identified and counted using immunofluorescence.The serum levels of D-lactic acid and zonulin were detected using enzyme-linked immunosorbent assay.RESULTS Compared to healthy controls,the staining of mucus secreted by goblet cells was darker in FC patients,and the number of goblet cells per upper crypt in the colonic mucosa was significantly increased in FC patients(control,18.67±2.99;FC,22.42±4.09;P=0.001).The intercellular junctional complexes in the colonic epithelium were integral in FC patients.The distribution of mucosal occludin and ZO-1 was not altered in FC patients.No significant differences were found in occludin(control,5.76E-2±1.62E-2;FC,5.17E-2±1.80E-2;P=0.240)and ZO-1展开更多
文摘AIM: To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. METHODS: Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A control group received the vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration. Intestinal permeability was evaluated by Evans blue and the FITC-dextran method. The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM). Mitochondrial function including mitochondrial swelling, mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were measured. Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. RESULTS: Compared with the control group, intestinal permeability was significantly increased in the diclofenac group, which was accompanied by broken tight junctions, and significant increases in MDA content and MPO activity. Rebamipide significantly reduced intestinal permeability, improved inter-cellular tight junctions, and was associated with decreases in intestinal MDA content and MPO activity. At the mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level and decreased mitochondrial swelling. CONCLUSION: Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.
基金Supported by the National Natural Science Foundation of China,No.81673795.
文摘BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients.However,they can also damage normal cells and cause serious intestinal toxicity,leading to gastrointestinal mucositis[1].Traditional Chinese medicine is effective in improving the side effects of chemotherapy.Wumei pills(WMP)was originally documented in the Treatise on Exogenous Febrile Diseases.It has a significant effect on chronic diarrhea and other gastrointestinal diseases,but it is not clear whether it affects chemotherapy induced intestinal mucositis(CIM).AIM To explore the potential mechanism of WMP in the treatment of CIM through experimental research.METHODS We used an intraperitoneal injection of 5-fluorouracil(5-Fu)to establish a CIM mouse model and an oral gavage of WMP decoction(11325 and 22650 mg/kg)to evaluate the efficacy of WMP in CIM.We evaluated the effect of WMP on CIM by observing the general conditions of the mice(body weight,food intake,spleen weight,diarrhea score,and hematoxylin and eosin stained tissues).The expression of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,and myeloperoxidase(MPO),as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB(TLR4/MyD88/NF-κB)signaling pathway proteins and tight junction proteins(zonula occludens-1,claudin-1,E-cadherin,and mucin-2)was determined.Furthermore,intestinal permeability,intestinal flora,and the levels of short-chain fatty acids(SCFA)were also assessed.RESULTS WMP effectively improved the body weight,spleen weight,food intake,diarrhea score,and inflammatory status of the mice with intestinal mucositis,which preliminarily confirmed the efficacy of WMP in CIM.Further experiments showed that in addition to reducing the levels of TNF-α,IL-1β,IL-6,and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins,WMP also repaired the integrity of the mucosal barrier of mice,regulated the intestinal flora,and increased the levels of SCFA(such as butyric acid).CONCLUSION WMP
基金the National Key Technology Support Program during“12th Five-Year Plan”Period of China,No.2014BAI08B00the Project“The role of the gut microbiota and metabolites in the pathogenesis of diarrheapredominant irritable bowel syndrome”of China-Japan Friendship Hospital,No.2019-64-K44.
文摘BACKGROUND The intestinal mucosal barrier is the first line of defense against numerous harmful substances,and it contributes to the maintenance of intestinal homeostasis.Recent studies reported that structural and functional changes in the intestinal mucosal barrier were involved in the pathogenesis of several intestinal diseases.However,no study thoroughly evaluated this barrier in patients with functional constipation(FC).AIM To investigate the intestinal mucosal barrier in FC,including the mucus barrier,intercellular junctions,mucosal immunity and gut permeability.METHODS Forty FC patients who fulfilled the Rome IV criteria and 24 healthy controls were recruited in the Department of Gastroenterology of China-Japan Friendship Hospital.The colonic mucus barrier,intercellular junctions in the colonic epithelium,mucosal immune state and gut permeability in FC patients were comprehensively examined.Goblet cells were stained with Alcian Blue/Periodic acid Schiff(AB/PAS)and counted.The ultrastructure of intercellular junctional complexes was observed under an electron microscope.Occludin and zonula occludens-1(ZO-1)in the colonic mucosa were located and quantified using immunohistochemistry and quantitative real-time polymerase chain reaction.Colonic CD3+intraepithelial lymphocytes(IELs)and CD3+lymphocytes in the lamina propria were identified and counted using immunofluorescence.The serum levels of D-lactic acid and zonulin were detected using enzyme-linked immunosorbent assay.RESULTS Compared to healthy controls,the staining of mucus secreted by goblet cells was darker in FC patients,and the number of goblet cells per upper crypt in the colonic mucosa was significantly increased in FC patients(control,18.67±2.99;FC,22.42±4.09;P=0.001).The intercellular junctional complexes in the colonic epithelium were integral in FC patients.The distribution of mucosal occludin and ZO-1 was not altered in FC patients.No significant differences were found in occludin(control,5.76E-2±1.62E-2;FC,5.17E-2±1.80E-2;P=0.240)and ZO-1
基金Research from the corresponding author’s laboratory was supported by grants from Merit-Review Award from US Department of Veterans Affairs and National Institutes of Health(NIH),USA(No.DK-57819,DK-61972,and DK-68491).
