AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang(TXYF) improves dysfunction in an irritable bowel syndrome(IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats(1...AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang(TXYF) improves dysfunction in an irritable bowel syndrome(IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats(1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine(5-HT) and substance P(SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity.in normal rats and 4.5 ± 1.58 in IBS model rats(P < 0.001). However, the defecation frequency was significantly decreased(3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time(in seconds) of colon transit function was significantly increased(256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. CONCLUSION: TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS.展开更多
BACKGROUND Tong Xie Yao Fang is a representative traditional Chinese prescription for the treatment of liver and spleen deficiency,abdominal pain and diarrhea.It has a unique function in the treatment of gastrointesti...BACKGROUND Tong Xie Yao Fang is a representative traditional Chinese prescription for the treatment of liver and spleen deficiency,abdominal pain and diarrhea.It has a unique function in the treatment of gastrointestinal dysfunction including irritable bowel syndrome(IBS),is a common functional bowel disease.Its main symptoms are recurrent abdominal pain,diarrhea,constipation or alternations between diarrhea and constipation.There are obvious differences in metabolites between TCM syndromes.By comparing the body fluid metabolism maps of model animals,metabolomics can discover disease biomarkers,analyze the differences in metabolic pathways and understand the pathological process and the metabolic pathways of substances in the body.Thus,the evaluation of animal models tends to be comprehensive and objective.This may provide further understanding between the interaction between Tong Xie Yao Fang and the IBS model.AIM To evaluate the effect of Tong Xie Yao Fang on IBS rats by using metabolomics method.METHODS Wistar rats were used to establish IBS models,and then randomly divided into four groups:A model control group and three Tong Xie Yao Fang treatment groups(high,medium and low doses).A normal,non-IBS group was established.The rats were treated for 2 wk.On days 0 and 14 of the experimental model,urine was collected for 12 h and was analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry.Nine potential biomarkers were identified,and six major metabolic pathways were found to be related to IBS.RESULTS In the study of metabonomics,nine potential biomarkers including L-serine,4-methylgallic acid,L-threonine,succinylacetone,prolyl-hydroxyproline,valylserine,acetyl citrate,marmesin rutinoside and 5-hydroxy-L-tryptophan were identified in urine,which were assigned to amino acids,organic acids,succinyl and glycosides.Furthermore,the metabolic pathway of L-serine,L-threonine and 5-hydroxy-L-tryptophan was found in the Kyoto Encyclopedia of Genes and Genomes,which mainly involved the metabolism of cysteine and methionine,vitamin B6 metabolism,serotonin synapse,tryptophan metabolism,sphingolipid metabolism,digestion,absorption of protein and amino acid metabolism.These pathways are related to intestinal dysfunction,inflammatory syndrome,nervous system dysfunction and other diseases.CONCLUSION Tong Xie Yao Fang has pharmacological effects on IBS,and its mechanism may be related to the metabolism of the nine potential biomarkers identified above in urine.展开更多
AIM To explore the significance of corticotropin-releasing hormone(CRH)-receptor(R)2 in mucosal healing of dextran sulfate sodium(DSS)-induced colitis and the effect of Tong-Xie-Yao-Fang(TXYF) on CRH-R2 expression and...AIM To explore the significance of corticotropin-releasing hormone(CRH)-receptor(R)2 in mucosal healing of dextran sulfate sodium(DSS)-induced colitis and the effect of Tong-Xie-Yao-Fang(TXYF) on CRH-R2 expression and regulation.METHODS Ulcerative colitis was induced in mice by administration of 3%(w/v) DSS for 7 d. Once the model was established,mice were administered urocortin-2(30 μg/kg), a peptide which binds exclusively to CRH-R2, or various doses of aqueous TXYF extracts(2.8-11.2 g/kg), a CRH-R2 antagonist Astressin(Ast)2B(20 μg/kg), Ast2B + Ucn2, or Ast2B with various doses of aqueous TXYF extracts for 9 d. Colonic mucosal permeability was then evaluated by measuring the fluorescence intensity in serum. The colitis disease activity index(DAI), histology, body weight loss and colon length were assessed to evaluate the condition of colitis. Terminal deoxynucleotidyl transferase d UTP nick-end labeling was used to detect apoptosis of the intestinal epithelial cells. The expression level of Ki-67 represented the proliferation of colonic epithelial cells and was detected by immunohistochemistry. The expression levels of inflammation cytokines IL-6, TNF-α and CXCL-1 were examined in colon tissues using real-time PCR and ELISA kits.RESULTS Compared with the DSS group, mice treated with the CRH-R2 antagonist Ast2B showed greater loss of body weight, shorter colon lengths(4.90 ± 0.32 vs 6.21 ± 0.34 cm, P < 0.05), and higher DAI(3.61 ± 0.53 vs 2.42 ± 0.32, P < 0.05) and histological scores(11.50 ± 1.05 vs 8.33 ± 1.03, P < 0.05). Additionally, the Ast2B group showed increased intestinal permeability(2.76 ± 0.11 μg/mL vs 1.47 ± 0.11 μg/mL, P < 0.001), improved secretion of inflammatory cytokines in colon tissue, and reduced colonic epithelial cell proliferation(4.97 ± 4.25 vs 22.51 ± 8.22, P < 0.05). Increased apoptosis(1422.39 ± 90.71 vs 983.01 ± 98.17, P < 0.001) was also demonstrated. The Ucn2 group demonstrated lower DAI(0.87 ± 0.55 vs 2.42 ± 0.32, P < 0.001) and histological scores(4.33 ± 1.50 vs 8.33 ± 1.03, P < 0.05). Diminished weight loss, longer colon length(9.58 ± 0.62 vs 6.21 ± 0.34 cm, P < 0.001), reduced intestinal permeability(0.75 ± 0.07 vs 1.47 ± 0.11 μg/mL, P < 0.001), inhibited secretion of inflammatory cytokines in colon tissue and increased colonic epithelial cell proliferation(90.04 ± 15.50 vs 22.51 ± 8.22, P < 0.01) were all observed. Reduced apoptosis(149.55 ± 21.68 vs 983.01 ± 98.17, P < 0.05) was also observed. However, significant statistical differences in the results of the Ast2 B group and Ast2 B + Ucn2 group were observed. TXYF was also found to ameliorate symptoms of DSS-induced colitis in mice and to promote mucosal repair like Ucn2. There were significant differences between the Ast2B + TXYF groups and the TXYF groups.CONCLUSION CRH-R2 activates the intestinal mucosal antiinflammatory response by regulating migration, proliferation and apoptosis of intestinal epithelial cells in colitisinduced mice, and plays an important antiinflammatory role. TXYF promotes mucosal repair in colitis mice by regulating CRH-R2.展开更多
BACKGROUND Solitary rectal ulcer syndrome(SRUS)is a rare rectal disorder characterized by bloody mucus in the stool,difficulty in defecation,pain,and anal swelling.To date,the etiology of this syndrome remains not wel...BACKGROUND Solitary rectal ulcer syndrome(SRUS)is a rare rectal disorder characterized by bloody mucus in the stool,difficulty in defecation,pain,and anal swelling.To date,the etiology of this syndrome remains not well understood and the diagnosis is frequently confused with other disorders,making treatment a clinical challenge.CASE SUMMARY A 50-year-old woman presented to our hospital with a 40-d history of bloody mucus in the stool and anal swelling.SRUS was suspected.Rectoscopy revealed a large,severe ulcerous lesion.Histologically,the lesion was characterized as chronic ulcer without clear tumor cells,and the final diagnosis of SRUS was made.The patient was treated with Chinese medicine therapy,with administration of Tong Xie Yao Fang.After 3 wk of treatment,the symptoms improved significantly.At 2-mo follow-up,rectoscopy in a local hospital showed healed ulcer scars without obvious protrusion 3 cm from the anal verge.CONCLUSION Chinese medicine therapy represents a potential treatment of SRUS with predominant rectal bleeding,mucinous discharge,and anal swelling pain.展开更多
背景肠易激综合征(IBS)是临床常见的肠道疾病,使用痛泻要方治疗确有疗效,但分析方剂中主要显效药物的相关研究较少。目的观察痛泻要方拆方对腹泻型肠易激综合征(IBS-D)大鼠结肠、海马体组织脑源性神经营养因子(BDNF)、P物质(SP)表达的...背景肠易激综合征(IBS)是临床常见的肠道疾病,使用痛泻要方治疗确有疗效,但分析方剂中主要显效药物的相关研究较少。目的观察痛泻要方拆方对腹泻型肠易激综合征(IBS-D)大鼠结肠、海马体组织脑源性神经营养因子(BDNF)、P物质(SP)表达的影响。方法于2020年7月选取6周龄SPF级雄性Wistar大鼠共32只,采用抽签法随机分为空白组、模型组、白芍防风组(B-F组)和陈皮白术组(C-B组),每组8只。除空白组外,其余各组均使用结直肠扩张+慢性束缚应激法建立内脏敏感型IBS-D大鼠模型。造模后B-F组采用白芍防风中药浸膏(4 ml/kg)灌胃治疗,C-B组采用陈皮白术中药浸膏(4 ml/kg)灌胃治疗,空白组和模型组采用蒸馏水灌胃,治疗周期为14 d。比较造模后、治疗后四组大鼠体质量及增长情况、布里斯托大便分类法评分、不同压力梯度下腹部撤退反射(AWR)、结肠及海马体组织中BDNF和SP表达水平的差异。结果建立IBS-D模型大鼠成功,所有大鼠存活。B-F组、C-B组大鼠造模后体质量增长量小于空白组,治疗后体质量增长量大于模型组(P<0.05)。模型组大鼠治疗后布里斯托大便分类法评分高于空白组(P<0.05);B-F组和C-B组大鼠治疗后布里斯托大便分类法评分低于模型组(P<0.05)。治疗后在气囊压力为60 mm Hg时:模型组大鼠AWR评分均高于空白组(P<0.05)。治疗后在气囊压力为60、80 mm Hg时:B-F组大鼠AWR评分低于模型组、C-B组(P<0.05)。模型组、C-B组大鼠治疗后结肠组织BDNF、SP表达水平高于空白组(P<0.05);B-F组大鼠治疗后结肠组织BDNF、SP表达水平低于模型组和C-B组(P<0.05)。模型组大鼠治疗后海马组织BDNF表达水平低于空白组(P<0.05);模型组、C-B组大鼠治疗后海马组织SP表达水平高于空白组(P<0.05);B-F组大鼠治疗后海马组织BDNF表达水平高于模型组,SP表达水平低于模型组(P<0.05)。结论痛泻要方中白芍防风药对、陈皮白术药对均能明显增加IBS-D大鼠体质量、改善腹泻情况。相较于陈皮白术药对,白芍防风药对可明显缓解IBS-D大鼠肠道高敏感,更好地下调海马组织SP和结肠组织BDNF、SP的表达,上调海马组织BDNF的表达,调节相关脑肠肽的平衡。展开更多
基金Supported by National Education Department"ChunHui Plan"Research Projects,No.Z2010021China Postdoctoral Science Foundation Project,No.2013M531079+2 种基金Heilongjiang Postdoctoral Funding Project,No.LBH-Z12246Heilongjiang Education Department Scientific Research Project,No.12521502excellent Innovative Talents Support Program Funding of Heilongjiang University of Chinese Medicine(Outstanding Young Academic Leaders),No.051217
文摘AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang(TXYF) improves dysfunction in an irritable bowel syndrome(IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats(1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine(5-HT) and substance P(SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity.in normal rats and 4.5 ± 1.58 in IBS model rats(P < 0.001). However, the defecation frequency was significantly decreased(3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time(in seconds) of colon transit function was significantly increased(256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. CONCLUSION: TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS.
基金Supported by the National Natural Science Foundation of China,No.81573870the Eighth Special Subsidy Project of China Post Doctoral Science Foundation,No.2015T80376+4 种基金Postdoctoral Science Research Developmental Foundation of China,No.2013M531079National Science Foundation of Heilongjiang Province,No.H2015020Heilongjiang University of Traditional Chinese Medicine Outstanding Innovative Talents Support Project(Outstanding Young Academic Leaders),Postdoctoral Science-Research Developmental Foundation of Heilongjiang Province,No.LBHQ12009Youth Academic Backbone Fund of Heilongjiang Province Education Department,No.1253G053Youth Science and Technology Project of Traditional Chinese Medicine Department of Heilongjiang Province,No.ZQG-034
文摘BACKGROUND Tong Xie Yao Fang is a representative traditional Chinese prescription for the treatment of liver and spleen deficiency,abdominal pain and diarrhea.It has a unique function in the treatment of gastrointestinal dysfunction including irritable bowel syndrome(IBS),is a common functional bowel disease.Its main symptoms are recurrent abdominal pain,diarrhea,constipation or alternations between diarrhea and constipation.There are obvious differences in metabolites between TCM syndromes.By comparing the body fluid metabolism maps of model animals,metabolomics can discover disease biomarkers,analyze the differences in metabolic pathways and understand the pathological process and the metabolic pathways of substances in the body.Thus,the evaluation of animal models tends to be comprehensive and objective.This may provide further understanding between the interaction between Tong Xie Yao Fang and the IBS model.AIM To evaluate the effect of Tong Xie Yao Fang on IBS rats by using metabolomics method.METHODS Wistar rats were used to establish IBS models,and then randomly divided into four groups:A model control group and three Tong Xie Yao Fang treatment groups(high,medium and low doses).A normal,non-IBS group was established.The rats were treated for 2 wk.On days 0 and 14 of the experimental model,urine was collected for 12 h and was analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry.Nine potential biomarkers were identified,and six major metabolic pathways were found to be related to IBS.RESULTS In the study of metabonomics,nine potential biomarkers including L-serine,4-methylgallic acid,L-threonine,succinylacetone,prolyl-hydroxyproline,valylserine,acetyl citrate,marmesin rutinoside and 5-hydroxy-L-tryptophan were identified in urine,which were assigned to amino acids,organic acids,succinyl and glycosides.Furthermore,the metabolic pathway of L-serine,L-threonine and 5-hydroxy-L-tryptophan was found in the Kyoto Encyclopedia of Genes and Genomes,which mainly involved the metabolism of cysteine and methionine,vitamin B6 metabolism,serotonin synapse,tryptophan metabolism,sphingolipid metabolism,digestion,absorption of protein and amino acid metabolism.These pathways are related to intestinal dysfunction,inflammatory syndrome,nervous system dysfunction and other diseases.CONCLUSION Tong Xie Yao Fang has pharmacological effects on IBS,and its mechanism may be related to the metabolism of the nine potential biomarkers identified above in urine.
基金Supported by National Natural Science Foundation of China,No.81473506Natural Science Foundation of Zhejiang Province,No.LY13H030011 and No.LY17H290009+2 种基金State Administration of Traditional Chinese Medicine of Zhejiang Province,No.2013ZB050Department of Zhejiang Province to Build Funded Project,No.WKJ-ZJ-1531Zhejiang TCM Science and Technology Project,No.2016ZB047,No.2017ZA056 and No.2018ZB046
文摘AIM To explore the significance of corticotropin-releasing hormone(CRH)-receptor(R)2 in mucosal healing of dextran sulfate sodium(DSS)-induced colitis and the effect of Tong-Xie-Yao-Fang(TXYF) on CRH-R2 expression and regulation.METHODS Ulcerative colitis was induced in mice by administration of 3%(w/v) DSS for 7 d. Once the model was established,mice were administered urocortin-2(30 μg/kg), a peptide which binds exclusively to CRH-R2, or various doses of aqueous TXYF extracts(2.8-11.2 g/kg), a CRH-R2 antagonist Astressin(Ast)2B(20 μg/kg), Ast2B + Ucn2, or Ast2B with various doses of aqueous TXYF extracts for 9 d. Colonic mucosal permeability was then evaluated by measuring the fluorescence intensity in serum. The colitis disease activity index(DAI), histology, body weight loss and colon length were assessed to evaluate the condition of colitis. Terminal deoxynucleotidyl transferase d UTP nick-end labeling was used to detect apoptosis of the intestinal epithelial cells. The expression level of Ki-67 represented the proliferation of colonic epithelial cells and was detected by immunohistochemistry. The expression levels of inflammation cytokines IL-6, TNF-α and CXCL-1 were examined in colon tissues using real-time PCR and ELISA kits.RESULTS Compared with the DSS group, mice treated with the CRH-R2 antagonist Ast2B showed greater loss of body weight, shorter colon lengths(4.90 ± 0.32 vs 6.21 ± 0.34 cm, P < 0.05), and higher DAI(3.61 ± 0.53 vs 2.42 ± 0.32, P < 0.05) and histological scores(11.50 ± 1.05 vs 8.33 ± 1.03, P < 0.05). Additionally, the Ast2B group showed increased intestinal permeability(2.76 ± 0.11 μg/mL vs 1.47 ± 0.11 μg/mL, P < 0.001), improved secretion of inflammatory cytokines in colon tissue, and reduced colonic epithelial cell proliferation(4.97 ± 4.25 vs 22.51 ± 8.22, P < 0.05). Increased apoptosis(1422.39 ± 90.71 vs 983.01 ± 98.17, P < 0.001) was also demonstrated. The Ucn2 group demonstrated lower DAI(0.87 ± 0.55 vs 2.42 ± 0.32, P < 0.001) and histological scores(4.33 ± 1.50 vs 8.33 ± 1.03, P < 0.05). Diminished weight loss, longer colon length(9.58 ± 0.62 vs 6.21 ± 0.34 cm, P < 0.001), reduced intestinal permeability(0.75 ± 0.07 vs 1.47 ± 0.11 μg/mL, P < 0.001), inhibited secretion of inflammatory cytokines in colon tissue and increased colonic epithelial cell proliferation(90.04 ± 15.50 vs 22.51 ± 8.22, P < 0.01) were all observed. Reduced apoptosis(149.55 ± 21.68 vs 983.01 ± 98.17, P < 0.05) was also observed. However, significant statistical differences in the results of the Ast2 B group and Ast2 B + Ucn2 group were observed. TXYF was also found to ameliorate symptoms of DSS-induced colitis in mice and to promote mucosal repair like Ucn2. There were significant differences between the Ast2B + TXYF groups and the TXYF groups.CONCLUSION CRH-R2 activates the intestinal mucosal antiinflammatory response by regulating migration, proliferation and apoptosis of intestinal epithelial cells in colitisinduced mice, and plays an important antiinflammatory role. TXYF promotes mucosal repair in colitis mice by regulating CRH-R2.
基金Supported by the Start-up Fund from Beijing University of Chinese Medicine,No.1000061020044
文摘BACKGROUND Solitary rectal ulcer syndrome(SRUS)is a rare rectal disorder characterized by bloody mucus in the stool,difficulty in defecation,pain,and anal swelling.To date,the etiology of this syndrome remains not well understood and the diagnosis is frequently confused with other disorders,making treatment a clinical challenge.CASE SUMMARY A 50-year-old woman presented to our hospital with a 40-d history of bloody mucus in the stool and anal swelling.SRUS was suspected.Rectoscopy revealed a large,severe ulcerous lesion.Histologically,the lesion was characterized as chronic ulcer without clear tumor cells,and the final diagnosis of SRUS was made.The patient was treated with Chinese medicine therapy,with administration of Tong Xie Yao Fang.After 3 wk of treatment,the symptoms improved significantly.At 2-mo follow-up,rectoscopy in a local hospital showed healed ulcer scars without obvious protrusion 3 cm from the anal verge.CONCLUSION Chinese medicine therapy represents a potential treatment of SRUS with predominant rectal bleeding,mucinous discharge,and anal swelling pain.
文摘背景肠易激综合征(IBS)是临床常见的肠道疾病,使用痛泻要方治疗确有疗效,但分析方剂中主要显效药物的相关研究较少。目的观察痛泻要方拆方对腹泻型肠易激综合征(IBS-D)大鼠结肠、海马体组织脑源性神经营养因子(BDNF)、P物质(SP)表达的影响。方法于2020年7月选取6周龄SPF级雄性Wistar大鼠共32只,采用抽签法随机分为空白组、模型组、白芍防风组(B-F组)和陈皮白术组(C-B组),每组8只。除空白组外,其余各组均使用结直肠扩张+慢性束缚应激法建立内脏敏感型IBS-D大鼠模型。造模后B-F组采用白芍防风中药浸膏(4 ml/kg)灌胃治疗,C-B组采用陈皮白术中药浸膏(4 ml/kg)灌胃治疗,空白组和模型组采用蒸馏水灌胃,治疗周期为14 d。比较造模后、治疗后四组大鼠体质量及增长情况、布里斯托大便分类法评分、不同压力梯度下腹部撤退反射(AWR)、结肠及海马体组织中BDNF和SP表达水平的差异。结果建立IBS-D模型大鼠成功,所有大鼠存活。B-F组、C-B组大鼠造模后体质量增长量小于空白组,治疗后体质量增长量大于模型组(P<0.05)。模型组大鼠治疗后布里斯托大便分类法评分高于空白组(P<0.05);B-F组和C-B组大鼠治疗后布里斯托大便分类法评分低于模型组(P<0.05)。治疗后在气囊压力为60 mm Hg时:模型组大鼠AWR评分均高于空白组(P<0.05)。治疗后在气囊压力为60、80 mm Hg时:B-F组大鼠AWR评分低于模型组、C-B组(P<0.05)。模型组、C-B组大鼠治疗后结肠组织BDNF、SP表达水平高于空白组(P<0.05);B-F组大鼠治疗后结肠组织BDNF、SP表达水平低于模型组和C-B组(P<0.05)。模型组大鼠治疗后海马组织BDNF表达水平低于空白组(P<0.05);模型组、C-B组大鼠治疗后海马组织SP表达水平高于空白组(P<0.05);B-F组大鼠治疗后海马组织BDNF表达水平高于模型组,SP表达水平低于模型组(P<0.05)。结论痛泻要方中白芍防风药对、陈皮白术药对均能明显增加IBS-D大鼠体质量、改善腹泻情况。相较于陈皮白术药对,白芍防风药对可明显缓解IBS-D大鼠肠道高敏感,更好地下调海马组织SP和结肠组织BDNF、SP的表达,上调海马组织BDNF的表达,调节相关脑肠肽的平衡。
