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OBJECTIVE To investigate the improvement effects of Runchang granules on the constipation in mice and its potential mechanism. METHODS The mice were randomly divided into normal control group， model group， Runchang granules low-dose and high-dose groups （5， 10 g/kg）， mosapride group （0.003 g/kg， positive control）， with 6 mice in each group. The latter 4 groups were given loperamide intragastrically （0.004 g/kg）， twice a day， for 3 consecutive days. Normal control group and model group were given purified water intragastrically， and administration groups were given relevant medicine intragastrically for 7 consecutive days. After the last medication， fecal moisture content and intestinal motility of mice were determined， while the structures of colon and ileum， and the secretion of colonic mucus were observed. Protein expressions of tyrosine kinase receptor （c-kit）， mucin 2 （MUC2） and stem cell factor （SCF） were determined in colon； meanwhile， the mRNA expression levels of inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， inducible nitric oxide synthase （iNOS）] as well as factors related to promoting intestinal motility [neuronal nitric oxide synthase （nNOS）， smooth muscle myosin light chain kinase （smMLCK）， 5-hydroxytryptamine 4 receptor （5-HT4R）， MUC2， SCF， c-kit] were determined. RESULTS Compared with model group， the fecal water content， intestinal propulsion rate， protein expression of c-kit in colon， relative expressions of MUC2 and SCF protein， and mRNA expressions of factors related to promoting intestinal motility （except for nNOS and SCF in Runchang granules low-dose group） were all increased significantly in Runchang granules low-dose and high-dose groups， and mosapride group （P＜0.05 or P＜0.01）. mRNA expression levels of inflammatory factors were decreased significantly（P＜0.05 or P＜0.01）. Both colon and ileum injuries improved， and the secretion of colon mucus was increased significantly in Runchang granules high-dose group （P＜0.01）. CONCLUSIONS Runchang granules have laxative effect and can improve constipation in mice， and its mechanism may be related to the promotion of the secretion of colon mucus and MUC2 expression， and the activation of SCF/c-kit signaling pathway.
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Mucin 2 (MUC2) is a kind of heavily glycosylated protein secreted by intestinal goblet cells. As the main component of intestinal mucus, MUC2 plays an important role in preventing the pathogenic microorganism from invasion as well as in assisting the colonization of intestinal probiotics. Intestinal flora is involved in many physiological functions of the human body. It modulates the synthesis, secretion and degradation of MUC2 through different mechanisms to affect the quality and quantity of MUC2. This article reviewed the effect and mechanism of intestinal flora on MUC2.
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AIM:To investigate the protective effect of mucin 2(MUC2)on intestinal mucosa of colitis model mice,and to explore the correlation between the expression of anti-CBir1 flagellin antibody and MUC2.METHODS:The mice were randomly divided into normal control group,2,4,6-trinitrobenzenesulfonic acid(TNBS)group,lipopolysaccha-ride(LPS)+ovalalbumin(OVA)+TNBS group and ketotifen+TNBS group.The expression of MUC2 in colon tissue was determined by PAS staining and immunohistochemistry, and the anti-CBir1 antibody level in the serum of mice in each group was measured by ELISA.RESULTS:The scores of disease activity index and histological index in TNBS group were higher than those in normal control group(P<0.05).The scores in LPS +OVA+TNBS group were much higher than those in TNBS group(P<0.05).However, the values in ketotifen +TNBS group were lower than those in TNBS group (P<0.05).PAS staining showed a decrease in goblet cells in TNBS group.Compared with TNBS group,the colonic mu-cosa integrity in LPS+OVA+TNBS group was destroyed, and the number of goblet cells in ketotifen +TNBS group in-creased significantly.Immunohistochemical staining showed that the expression of MUC 2 in the intestinal tract of each mo-del group was basically consistent with the results of PAS staining.The serum anti-CBir1 antibody level in TNBS group was higher than that in normal control group(P<0.05), and that in LPS+OVA+TNBS group was significantly higher than that in TNBS group(P<0.05),whereas that in ketotifen +TNBS group was decreased slightly(P<0.05).CONCLU-SION:MUC2 plays a protective role in the pathogenesis of colitis in mice,and there is a negative correlation between the expression of MUC2 and the bacterial flagellin in the intestinal mucosa of mice with colitis.
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Objective To investigate the function of mucin 2,mucin 4 on formation of lithogenic bile in patients with calculus of intrahepatic duct.Methods Bile duct mucosa,bile duct wall,bile and plasma were collected from 56 patients with calculus of intrahepatic duct (CID group) and 17 individuals without calculus of intrahepatic duct (control group).The bile duct wall was stained with mucin 2 (MUC2) and mucin 4 (MUC4).Reverse-transcription polymerase chain reaction (RT-PCR) was applied to study the mRNA expressions of MUC2 and MUC4 in the bile duct mucosa.The correlation of the bile duct and serum lipid index was analyzed.Results Serum lipid index in the CID group was significantly higher than control group (all P＜0.05).Biliary total bile acids and bile acids mol percentage were lower in the CID group than control group (both P＜0.05).The expressions of MUC2 was not increased significantly in CID group than the control group (all P＞0.05).The expressions of MUC4 were more significantly increased in CID group than the control group (P＜0.05).The mRNA of MUC4 in the CID group was also more significantly increased than in control group (P＜0.01).There were no correlations between MUC4 expression and the level of biliary total bile acid in the CID group (r=-0.374,P＜0.05).Conclusion The expression of MUC4 in patients with CID was enhanced,which promoted the absorption of bile acid by the mucosal epithelium of the bile duct,and caused a large amount of mucin to be secreted into bile,which may be related to the formation of stony bile.
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ABSTRACT Background: The effects of topical application of sucralfate (SCF) on the tissue content of MUC-2 protein have not yet been evaluated in experimental models of diversion colitis. Aim: To measure the tissue content of MUC-2 protein in the colonic mucosa diverted from fecal stream submitted to the SCF intervention. Methods: Thirty-six rats underwent derivation of intestinal transit through proximal colostomy and distal mucous fistula. The animals were divided into three groups which were submitted application of enemas with saline, SCF 1 g/kg/day and SCF 2 g/kg/day. Each group was divided into two subgroups, according to euthanasia was done after two or four weeks. The colitis diagnosis was established by histopathological study and the inflammatory intensity was evaluated by previously validated scale. The MUC-2 protein was identified by immunohistochemistry and the tissue content was measured computerized morphometry). Results: The application of enemas with SCF in the concentration of 2 g/kg/day reduced inflammatory score of the segments that were diverted from fecal stream. The content of MUC-2 in diverted colon of the animals submitted to the intervention with SCF, independently of intervention period and the used concentration, was significantly greater than animals submitted to the application of enemas containing saline (p< 0.01). The content of MUC-2 after the intervention with SCF in the concentration of 2 g/kg/day was significantly higher when compared to the animals submitted to the application containing SCF at concentration of 1.0 g/kg/day (p<0.01). The tissue content of MUC-2 reached the highest values after intervention with SCF in the concentration of 2 g/kg/day for four weeks (p<0.01). Conclusion: The preventive application of enemas containing SCF reduces the inflammatory score and avoids the reduction of tissue content of MUC-2, suggesting that the substance is a valid therapeutic strategy to preserve the mucus layer that covers the intestinal epithelium.
RESUMO Racional: Os efeitos da aplicação tópica de sucralfato (SCF) no conteúdo tecidual da proteína mucina-2 (MUC-2) ainda não foram avaliados em modelos experimentais de colite de exclusão. Objetivo: Mensurar o conteúdo tecidual da proteína MUC-2 na mucosa cólica sem trânsito intestinal submetida à intervenção com SCF. Método: Trinta e seis ratos foram submetidos à derivação intestinal por colostomia proximal terminal e fístula mucosa distal. Foram divididos em três grupos segundo recebessem clisteres contendo solução fisiológica (SF), SCF 1 g/kg/dia e SCF 2 g/kg/dia. Cada grupo foi dividido em dois subgrupos, segundo a eutanásia ser realizada após duas ou quatro semanas. O diagnóstico de colite foi estabelecido por estudo histopatológico e a intensidade inflamatória foi avaliada por escala validada. A expressão tecidual da MUC-2 foi identificada por imunoistoquímica e seu conteúdo mensurado por morfometria computadorizada. Resultados: A aplicação de clisteres com SCF na concentração de 2 g/kg/dia reduziu a intensidade inflamatória no cólon sem trânsito fecal. O conteúdo tecidual de MUC-2 no cólon sem trânsito dos animais submetidos à intervenção com SCF, independente do tempo de intervenção e da concentração utilizada, foi maior quando comparado aos animais tratados com SF (p<0,01). O conteúdo de MUC-2 após a intervenção com SCF na concentração de 2 g/kg/dia foi maior quando comparado aos animais submetidos à intervenção com concentração menor (p<0,01). O conteúdo de MUC-2 foi maior após intervenção com SCF na concentração de 2 g/kg/dia por quatro semanas (p<0,01). Conclusão: A aplicação preventiva de clisteres com SCF reduz o grau de inflamação e preserva o conteúdo tecidual de MUC-2, em segmentos desprovidos de trânsito intestinal, mostrando-se uma estratégia terapêutica válida para preservar a camada de muco que recobre o epitélio intestinal.
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ABSTRACT Background: The effects of topical application of sucralfate (SCF) on the tissue content of MUC-2 protein have not yet been evaluated in experimental models of diversion colitis. Aim: To measure the tissue content of MUC-2 protein in the colonic mucosa diverted from fecal stream submitted to the SCF intervention. Methods: Thirty-six rats underwent derivation of intestinal transit through proximal colostomy and distal mucous fistula. The animals were divided into three groups which were submitted application of enemas with saline, SCF 1 g/kg/day and SCF 2 g/kg/day. Each group was divided into two subgroups, according to euthanasia was done after two or four weeks. The colitis diagnosis was established by histopathological study and the inflammatory intensity was evaluated by previously validated scale. The MUC-2 protein was identified by immunohistochemistry and the tissue content was measured computerized morphometry). Results: The application of enemas with SCF in the concentration of 2 g/kg/day reduced inflammatory score of the segments that were diverted from fecal stream. The content of MUC-2 in diverted colon of the animals submitted to the intervention with SCF, independently of intervention period and the used concentration, was significantly greater than animals submitted to the application of enemas containing saline (p< 0.01). The content of MUC-2 after the intervention with SCF in the concentration of 2 g/kg/day was significantly higher when compared to the animals submitted to the application containing SCF at concentration of 1.0 g/kg/day (p<0.01). The tissue content of MUC-2 reached the highest values after intervention with SCF in the concentration of 2 g/kg/day for four weeks (p<0.01). Conclusion: The preventive application of enemas containing SCF reduces the inflammatory score and avoids the reduction of tissue content of MUC-2, suggesting that the substance is a valid therapeutic strategy to preserve the mucus layer that covers the intestinal epithelium.
RESUMO Racional: Os efeitos da aplicação tópica de sucralfato (SCF) no conteúdo tecidual da proteína mucina-2 (MUC-2) ainda não foram avaliados em modelos experimentais de colite de exclusão. Objetivo: Mensurar o conteúdo tecidual da proteína MUC-2 na mucosa cólica sem trânsito intestinal submetida à intervenção com SCF. Método: Trinta e seis ratos foram submetidos à derivação intestinal por colostomia proximal terminal e fístula mucosa distal. Foram divididos em três grupos segundo recebessem clisteres contendo solução fisiológica (SF), SCF 1 g/kg/dia e SCF 2 g/kg/dia. Cada grupo foi dividido em dois subgrupos, segundo a eutanásia ser realizada após duas ou quatro semanas. O diagnóstico de colite foi estabelecido por estudo histopatológico e a intensidade inflamatória foi avaliada por escala validada. A expressão tecidual da MUC-2 foi identificada por imunoistoquímica e seu conteúdo mensurado por morfometria computadorizada. Resultados: A aplicação de clisteres com SCF na concentração de 2 g/kg/dia reduziu a intensidade inflamatória no cólon sem trânsito fecal. O conteúdo tecidual de MUC-2 no cólon sem trânsito dos animais submetidos à intervenção com SCF, independente do tempo de intervenção e da concentração utilizada, foi maior quando comparado aos animais tratados com SF (p<0,01). O conteúdo de MUC-2 após a intervenção com SCF na concentração de 2 g/kg/dia foi maior quando comparado aos animais submetidos à intervenção com concentração menor (p<0,01). O conteúdo de MUC-2 foi maior após intervenção com SCF na concentração de 2 g/kg/dia por quatro semanas (p<0,01). Conclusão: A aplicação preventiva de clisteres com SCF reduz o grau de inflamação e preserva o conteúdo tecidual de MUC-2, em segmentos desprovidos de trânsito intestinal, mostrando-se uma estratégia terapêutica válida para preservar a camada de muco que recobre o epitélio intestinal.
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ABSTRACT Background: The effects of topical application of sucralfate (SCF) on the tissue content of MUC-2 protein have not yet been evaluated in experimental models of diversion colitis. Aim: To measure the tissue content of MUC-2 protein in the colonic mucosa diverted from fecal stream submitted to the SCF intervention. Methods: Thirty-six rats underwent derivation of intestinal transit through proximal colostomy and distal mucous fistula. The animals were divided into three groups which were submitted application of enemas with saline, SCF 1 g/kg/day and SCF 2 g/kg/day. Each group was divided into two subgroups, according to euthanasia was done after two or four weeks. The colitis diagnosis was established by histopathological study and the inflammatory intensity was evaluated by previously validated scale. The MUC-2 protein was identified by immunohistochemistry and the tissue content was measured computerized morphometry). Results: The application of enemas with SCF in the concentration of 2 g/kg/day reduced inflammatory score of the segments that were diverted from fecal stream. The content of MUC-2 in diverted colon of the animals submitted to the intervention with SCF, independently of intervention period and the used concentration, was significantly greater than animals submitted to the application of enemas containing saline (p< 0.01). The content of MUC-2 after the intervention with SCF in the concentration of 2 g/kg/day was significantly higher when compared to the animals submitted to the application containing SCF at concentration of 1.0 g/kg/day (p<0.01). The tissue content of MUC-2 reached the highest values after intervention with SCF in the concentration of 2 g/kg/day for four weeks (p<0.01). Conclusion: The preventive application of enemas containing SCF reduces the inflammatory score and avoids the reduction of tissue content of MUC-2, suggesting that the substance is a valid therapeutic strategy to preserve the mucus layer that covers the intestinal epithelium.
RESUMO Racional: Os efeitos da aplicação tópica de sucralfato (SCF) no conteúdo tecidual da proteína mucina-2 (MUC-2) ainda não foram avaliados em modelos experimentais de colite de exclusão. Objetivo: Mensurar o conteúdo tecidual da proteína MUC-2 na mucosa cólica sem trânsito intestinal submetida à intervenção com SCF. Método : Trinta e seis ratos foram submetidos à derivação intestinal por colostomia proximal terminal e fístula mucosa distal. Foram divididos em três grupos segundo recebessem clisteres contendo solução fisiológica (SF), SCF 1 g/kg/dia e SCF 2 g/kg/dia. Cada grupo foi dividido em dois subgrupos, segundo a eutanásia ser realizada após duas ou quatro semanas. O diagnóstico de colite foi estabelecido por estudo histopatológico e a intensidade inflamatória foi avaliada por escala validada. A expressão tecidual da MUC-2 foi identificada por imunoistoquímica e seu conteúdo mensurado por morfometria computadorizada. Resultados: A aplicação de clisteres com SCF na concentração de 2 g/kg/dia reduziu a intensidade inflamatória no cólon sem trânsito fecal. O conteúdo tecidual de MUC-2 no cólon sem trânsito dos animais submetidos à intervenção com SCF, independente do tempo de intervenção e da concentração utilizada, foi maior quando comparado aos animais tratados com SF (p<0,01). O conteúdo de MUC-2 após a intervenção com SCF na concentração de 2 g/kg/dia foi maior quando comparado aos animais submetidos à intervenção com concentração menor (p<0,01). O conteúdo de MUC-2 foi maior após intervenção com SCF na concentração de 2 g/kg/dia por quatro semanas (p<0,01). Conclusão: A aplicação preventiva de clisteres com SCF reduz o grau de inflamação e preserva o conteúdo tecidual de MUC-2, em segmentos desprovidos de trânsito intestinal, mostrando-se uma estratégia terapêutica válida para preservar a camada de muco que recobre o epitélio intestinal.
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Animals , Male , Rats , Sucralfate , Colitis/metabolism , Colon/chemistry , Enema , Mucin-2/analysis , Intestinal Mucosa/chemistry , Rats, WistarABSTRACT
Background:Acute pancreatitis can induce intestinal barrier dysfunction in its early phase,which is closely related with the progression and prognosis of the disease. Intestinal mucus layer not only serves as a physical barrier between pathogens and epithelium,but also plays a critical role in the maintenance of intestinal barrier function. Aims:To investigate the expression and role of mucin 2 (MUC2)in injured intestinal barrier in rats with acute necrotizing pancreatitis (ANP). Methods:Forty-two male Sprague-Dawley rats were randomly divided into two groups:the sham operation (SO)group and ANP group,which were induced via a retrograde injection of 3. 5% sodium taurocholate into biliopancreatic duct. Blood,pancreas and colon samples were obtained 6,12 and 24 hours after establishing the ANP model for determination of serum amylase and D-lactate (an indicator of intestinal permeability)and histopathological examination. PAS/ AB staining was used to observe the colon mucus layer and goblet cells,and the expressions of MUC2 and inflammatory cytokines in colonic tissue were detected by real-time PCR. Results:ANP models were successfully established. In ANP group,obvious colonic injury,increased intestinal permeability,thinner colon mucus layer,reduced mucin-containing goblet cells,down-regulated MUC2 mRNA and up-regulated tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β)and interferon-γ (IFN-γ)mRNAs were observed at each time point as compared with those in SO group (P < 0. 05). Spearman correlation coefficient revealed that MUC2 expression was negatively correlated with the intestinal permeability and expression of inflammatory cytokines in ANP group (P < 0. 05). Conclusions:Transcription of MUC2 is significantly down-regulated in colonic tissue of ANP rats,and might be associated with increased intestinal permeability and excessive expression of inflammatory cytokines in early phase of ANP.
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Background:TLR4 can mediate immune and inflammatory responses,TFF3,MUC2 are the intestinal mucosa protection factor and can maintain the intestinal barrier function. Aims:To investigate the effect of Anchang Yuyang decoction on colon tissue TFF3,MUC2 and TLR4 gene expressions in rats with ulcerative colitis. Methods:TNBS was used to establish ulcerative colitis model in rats. Ninety Wistar rats were randomly divided into normal control group,model group,low,moderate and high dose Anchang Yuyang decoction groups and mesalazine group,and distilled water,different concentrations of Anchang Yuyang decoction and mesalazine were given respectively. All the rats were sacrificed after 21 days. Colonic histopathological score was assessed,and RT-PCR was used to detect gene expressions of colon tissue TFF3, MUC2 and TLR4. Results:Compared with model group,histopathological score and TLR4 expression were significantly decreased in moderate,high dose Anchang Yuyang decoction groups and mesalazine group(P < 0. 05),expressions of TFF3 and MUC2 were significantly increased( P < 0. 05). Compared with moderate dose Anchang Yuyang decoction group,histopathological score in high dose Anchang Yuyang decoction group and mesalazine group was significantly decreased(P < 0. 05),and TFF3 expression was significantly increased( P < 0. 01). Compared with moderate dose Anchang Yuyang decoction group and mesalazine group,MUC2 expression in high dose Anchang Yuyang decoction group was significantly increased(P < 0. 01),and TLR4 expression was significantly decreased( P < 0. 01). Conclusions:Anchang Yuyang decoction can promote the repair of colonic mucosa in rats with ulcerative colitis,and its mechanism may be related to the increase of TFF3 and MUC2 gene expressions and down regulation of TLR4 gene expression.
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Objective To study the significance of Helicobacter pylori (Hp) infection and the expression of caudal-related homeobox transcription factor 2 (CDX2),mucin 2 (MUC2) proteins in gastric cancer,and elucidate the prognostic significance of CDX2,MUC2 proteins in gastric cancer.Methods Ninety cases of gastric cancer were available for the study.Hp was studied by Warthin-Starry bacterium stain and CDX2 and MUC2 proteins were studied by immunohistochemical stain.Results There was no Hp infection and no expression of CDX2 and MUC2 proteins in normal gastric mucosa.The positive rate in the cases of intestinal-type gastric cancer was 67.86%(38/56) for Hp,75.00% (42/56) for CDX2,and 66.07%(37/56) for MUC2,respectively,and it was higher than that in the cases of diffuse-type gastric cancer,which was 35.29%(12/34),41.18%(14/34) and 38.24%(13/34) respectively (P<0.01 or < 0.05).In intestinaltype gastric cancer,the positive rate of CDX2 and MUC2 proteins was also higher in Hp positive cases than that in Hp negative cases,and it was the same as CDX2 protein in diffuse-type gastric cancer.Higher positive rates of CDX2 and MUC2 proteins were observed in the cases of early gastric cancer than those in the cases of advanced gastric cancer (P < 0.01 or < 0.05),also it was observed in the cases of no lymph node metastasis than in the cases of lymph node metastasis (P < 0.01 or < 0.05).Moreover,the positive rate of CDX2 protein in the cases of stage Ⅰ～Ⅱwas higher than that in the cases of stage Ⅲ～Ⅳ (P < 0.05).Conclusions Hp infection and the expression of CDX2 and MUC2 proteins are related with gastric cancer,and has close relationship with intestinal-type gastric cancer.The expressions of CDX2 and MUC2 proteins may inhibit the infiltration and metastasis of gastric cancer.