BACKGROUND About one-third of refractory irritable bowel syndrome(IBS)cases are caused by gastrointestinal(GI)infection/inflammation,known as post-infectious/postinflammatory IBS(PI-IBS).Although it is known that inte...BACKGROUND About one-third of refractory irritable bowel syndrome(IBS)cases are caused by gastrointestinal(GI)infection/inflammation,known as post-infectious/postinflammatory IBS(PI-IBS).Although it is known that intestinal microbiota and host NOD-like receptor family pyrin domain containing 6(NLRP6)inflammsome signaling are closely related to PI-IBS and moxibustion has a therapeutic effect on PI-IBS,whether moxibustion regulates the intestinal flora and host NLRP6 events in PI-IBS remains unclear.AIM To examine the regulatory effect of moxibustion on intestinal microbiota and host NLRP6 inflammatory signaling in PI-IBS.METHODS Sprague-Dawley rats were divided into a normal control group,a model control group,a mild moxibustion group,and a sham mild moxibustion group.PI-IBS rats in the mild moxibustion group were treated with moxibusiton at bilateral Tianshu(ST 25)and Zusanli(ST36)for 7 consecutive days for 10 min each time.The sham group rats were given the same treatment as the mild moxibustion group except the moxa stick was not ignited.Abdominal withdrawal reflex(AWR)score was measured to assess the visceral sensitivity,and colon histopathology and ultrastructure,colonic myeloperoxidase(MPO)activity,and serum C-reactive protein(CRP)level were measured to evaluate low-grade colonic inflammation in rats.The relative abundance of selected intestinal bacteria in rat feces was detected by 16S rDNA PCR and the NLRP6 inflammsome signaling in the colon was detected by immunofluorescence,qRTPCR,and Western blot.RESULTS The AWR score was significantly decreased and the low-grade intestinal inflammation reflected by serum CRP and colonic MPO levels was inhibited in the mild moxibustion group compared with the sham group.Mild moxibustion remarkably increased the relative DNA abundances of Lactobacillus,Bifidobacterium,and Faecalibacterium prausnitzii but decreased that of Escherichia coli in the gut of PI-IBS rats.Additionally,mild moxibustion induced mRNA and protein expression of intestine lectin 1 but inhibited the ex展开更多
Chemerin is present in various inflammatory sites and is closely involved in tissue inflammation. Recent studies have demonstrated that chemerin treatment can cause either anti-inflammatory or pro-inflammatory effects...Chemerin is present in various inflammatory sites and is closely involved in tissue inflammation. Recent studies have demonstrated that chemerin treatment can cause either anti-inflammatory or pro-inflammatory effects according to the disease model being investigated. Elevated circulating chemerin was recently found in patients with inflammatory bowel disease （IBD）; however, the role of chemerin in intestinal inflammation remains unknown. In this study, we demonstrated that the administration of exogenous chemerin （aa 17-156） aggravated the severity of dextran sulfate sodium （DSS）-induced colitis, which was characterized by higher clinical scores, extensive mucosal damage and significantly increased local and systemic production of pro-inflammatory cytokines, including IL-6, TNF-a and interferon （IFN-7）. Interestingly, chemerin did not appear to influence the magnitudes of inflammatory infiltrates in the colons, but did result in significantly decreased colonic expression of M2 macrophage-associated genes, including Arginase 1 （Arg-1）, Yml, FIZZ1 and IL-IO, following DSS exposure, suggesting an impaired M2 macrophage skewing in vivo. Furthermore, an in vitro experiment showed that the addition of chemerin directly suppressed M2 macrophage-associated gene expression and STAT6 phosphorylation in IL-4-stimulated macrophages. Significantly elevated chemerin levels were found in colons from DSS-exposed mice and from ulcerative colitis （UC） patients and appeared to positively correlate with disease severity. Moreover, the in vivo administration of neutralizing anti-chemerin antibody significantly improved intestinal inflammation following DSS exposure. Taken together, our findings reveal a pro-inflammatory role for chemerin in DSS-induced colitis and the ability of chemerin to suppress the anti-inflammatory M2 macrophage response. Our study also suggests that upregulated chemerin in inflamed colons may contribute to the pathogenesis of IBD.展开更多
Although the incidence of Crohn's disease(CD) in China is not as high as that in European and American countries, there has been a clear increasing trend in recent years. Little is known about its pathogenesis, ca...Although the incidence of Crohn's disease(CD) in China is not as high as that in European and American countries, there has been a clear increasing trend in recent years. Little is known about its pathogenesis, cause of deferment, and the range of complications associated with the disease. Local and international scholars have presented many hypotheses about CD pathogenesis based on experimental and clinical studies, including genetic susceptibility, immune function defects, intestinal microflora disorders, delayed hypersensitivity, and food antigen stimulation. However, the specific mechanism leading to this immune imbalance, which causes persistent intestinal mucosal damage, and the source of the inflammatory cascade reaction are still unclear. So far, the results of research studies differ locally and internationally. This paper presents the most current research on immune factors in the pathogenesis of CD.展开更多
目的:探讨抑郁焦虑情绪与肠道炎症疾病之间存在的交互作用及其可能的机制。方法:建立大鼠慢性应激模型(应激组)、肠道炎症模型(肠道炎症组)、应激加肠道炎症模型(应激+肠道炎症组),并设正常组。采用强迫游泳实验和大理石掩埋实验评估动...目的:探讨抑郁焦虑情绪与肠道炎症疾病之间存在的交互作用及其可能的机制。方法:建立大鼠慢性应激模型(应激组)、肠道炎症模型(肠道炎症组)、应激加肠道炎症模型(应激+肠道炎症组),并设正常组。采用强迫游泳实验和大理石掩埋实验评估动物抑郁焦虑样行为;采用排便颗粒数及腹壁撤退反射(AWR)评估动物肠道动力情况与内脏敏感性;采用Western blot法分析大鼠脑内及肠道内蛋白表达情况。结果:应激+肠道炎症组游泳不动时间抑制率为108.4%,远大于应激组的50.2%;应激+肠道炎症组的大理石掩埋颗粒数抑制率为211.6%,远大于应激组的112.3%。应激+肠道炎症组排便颗粒数增加的抑制率为131.4%,远大于肠道炎症组的97.1%;在内脏敏感性实验中,无论在60 mm Hg还是在80 mm Hg时,应激+肠道炎症组的AWR抑制率均大于肠道炎症组。应激+肠道炎症组大鼠海马及额叶皮层内脑源性神经营养因子(BDNF)、磷酸化环磷腺苷效应元件结合蛋白(p-CREB)表达降低较应激组更为显著;应激+肠道炎症组回肠及结肠内炎症因子IL-1β、IL-6表达升高均较肠道炎症组更为显著。结论:抑郁焦虑等情绪可通过调节肠内IL-1β及IL-6表达加重肠道功能紊乱,而肠道功能的紊乱又可通过调节脑内BDNF水平及降低环磷腺苷效应元件结合蛋白(CREB)的磷酸化加重抑郁焦虑等情绪,即抑郁焦虑情绪和肠道炎症两者之间具有一定程度的交互作用。展开更多
肠道是营养物质消化吸收的主要部位,但易受外界环境刺激引起病理变化。动物肠道疾病的多发严重影响着动物的生长发育过程,增加动物的饲养成本,对养殖业的经济效益造成巨大冲击。虽然抗生素是缓解肠道疾病发生发展的有效策略,但因其耐药...肠道是营养物质消化吸收的主要部位,但易受外界环境刺激引起病理变化。动物肠道疾病的多发严重影响着动物的生长发育过程,增加动物的饲养成本,对养殖业的经济效益造成巨大冲击。虽然抗生素是缓解肠道疾病发生发展的有效策略,但因其耐药性以及药物残留等问题让人们不得不开发新的环境友好型替代产品。植物多糖广泛存在于自然界的植物中,具有高效、无毒副作用、无残留等特点。植物多糖作为绿色饲料添加剂,在保护动物肠道健康、提高动物生长性能方面发挥重要作用,其主要通过调控核因子-κB(nuclear factor kappaB,NF-κB)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)、Janus激酶/信号转导和转录激活因子(Janus kinase/signal transducer and activator of transcription,JAK/STAT)、转化生长因子-β(transforming growth factor-β,TGF-β)、磷脂酰肌醇-3-激酶/蛋白激酶B(phosphatidylinositol-3-kinase/protein kinase B,PI3K/Akt)等信号通路来充分发挥肠道各屏障的生理功能以及加强各屏障之间的相互联系,预防动物肠道疾病发生,调节肠道炎症水平,维持肠道微生物区系平衡,提升机体抗氧化能力,增强动物机体免疫性能,进而在一定程度上改善畜产品品质,提升动物创造的经济价值。作者综述了植物多糖对动物肠道的保护作用及其分子机制,并阐述了其在动物生产实践中的应用及取得的效果,旨在为植物多糖在动物生产中的应用提供参考。展开更多
基金Supported by the National Natural Science Foundation of China,No.81503656the National Key Basic Research Program of China(973 Program),No.2015CB554501 and No.2009CB522900
文摘BACKGROUND About one-third of refractory irritable bowel syndrome(IBS)cases are caused by gastrointestinal(GI)infection/inflammation,known as post-infectious/postinflammatory IBS(PI-IBS).Although it is known that intestinal microbiota and host NOD-like receptor family pyrin domain containing 6(NLRP6)inflammsome signaling are closely related to PI-IBS and moxibustion has a therapeutic effect on PI-IBS,whether moxibustion regulates the intestinal flora and host NLRP6 events in PI-IBS remains unclear.AIM To examine the regulatory effect of moxibustion on intestinal microbiota and host NLRP6 inflammatory signaling in PI-IBS.METHODS Sprague-Dawley rats were divided into a normal control group,a model control group,a mild moxibustion group,and a sham mild moxibustion group.PI-IBS rats in the mild moxibustion group were treated with moxibusiton at bilateral Tianshu(ST 25)and Zusanli(ST36)for 7 consecutive days for 10 min each time.The sham group rats were given the same treatment as the mild moxibustion group except the moxa stick was not ignited.Abdominal withdrawal reflex(AWR)score was measured to assess the visceral sensitivity,and colon histopathology and ultrastructure,colonic myeloperoxidase(MPO)activity,and serum C-reactive protein(CRP)level were measured to evaluate low-grade colonic inflammation in rats.The relative abundance of selected intestinal bacteria in rat feces was detected by 16S rDNA PCR and the NLRP6 inflammsome signaling in the colon was detected by immunofluorescence,qRTPCR,and Western blot.RESULTS The AWR score was significantly decreased and the low-grade intestinal inflammation reflected by serum CRP and colonic MPO levels was inhibited in the mild moxibustion group compared with the sham group.Mild moxibustion remarkably increased the relative DNA abundances of Lactobacillus,Bifidobacterium,and Faecalibacterium prausnitzii but decreased that of Escherichia coli in the gut of PI-IBS rats.Additionally,mild moxibustion induced mRNA and protein expression of intestine lectin 1 but inhibited the ex
基金ACKNOWLEDGEMENTS We thank Dr Hongguang Zhu from the Department of Pathology, Fudan University for his useful advice on the histological analysis. This work was supported by the National Natural Science Foundation of China Grant 81172797 （to RH） and the Program of Shanghai Pujiang Talent 11PJ1400400 （to RH）.
文摘Chemerin is present in various inflammatory sites and is closely involved in tissue inflammation. Recent studies have demonstrated that chemerin treatment can cause either anti-inflammatory or pro-inflammatory effects according to the disease model being investigated. Elevated circulating chemerin was recently found in patients with inflammatory bowel disease （IBD）; however, the role of chemerin in intestinal inflammation remains unknown. In this study, we demonstrated that the administration of exogenous chemerin （aa 17-156） aggravated the severity of dextran sulfate sodium （DSS）-induced colitis, which was characterized by higher clinical scores, extensive mucosal damage and significantly increased local and systemic production of pro-inflammatory cytokines, including IL-6, TNF-a and interferon （IFN-7）. Interestingly, chemerin did not appear to influence the magnitudes of inflammatory infiltrates in the colons, but did result in significantly decreased colonic expression of M2 macrophage-associated genes, including Arginase 1 （Arg-1）, Yml, FIZZ1 and IL-IO, following DSS exposure, suggesting an impaired M2 macrophage skewing in vivo. Furthermore, an in vitro experiment showed that the addition of chemerin directly suppressed M2 macrophage-associated gene expression and STAT6 phosphorylation in IL-4-stimulated macrophages. Significantly elevated chemerin levels were found in colons from DSS-exposed mice and from ulcerative colitis （UC） patients and appeared to positively correlate with disease severity. Moreover, the in vivo administration of neutralizing anti-chemerin antibody significantly improved intestinal inflammation following DSS exposure. Taken together, our findings reveal a pro-inflammatory role for chemerin in DSS-induced colitis and the ability of chemerin to suppress the anti-inflammatory M2 macrophage response. Our study also suggests that upregulated chemerin in inflamed colons may contribute to the pathogenesis of IBD.
基金Supported by the National Natural Science Foundation of China,No.81570503
文摘Although the incidence of Crohn's disease(CD) in China is not as high as that in European and American countries, there has been a clear increasing trend in recent years. Little is known about its pathogenesis, cause of deferment, and the range of complications associated with the disease. Local and international scholars have presented many hypotheses about CD pathogenesis based on experimental and clinical studies, including genetic susceptibility, immune function defects, intestinal microflora disorders, delayed hypersensitivity, and food antigen stimulation. However, the specific mechanism leading to this immune imbalance, which causes persistent intestinal mucosal damage, and the source of the inflammatory cascade reaction are still unclear. So far, the results of research studies differ locally and internationally. This paper presents the most current research on immune factors in the pathogenesis of CD.
文摘目的:探讨抑郁焦虑情绪与肠道炎症疾病之间存在的交互作用及其可能的机制。方法:建立大鼠慢性应激模型(应激组)、肠道炎症模型(肠道炎症组)、应激加肠道炎症模型(应激+肠道炎症组),并设正常组。采用强迫游泳实验和大理石掩埋实验评估动物抑郁焦虑样行为;采用排便颗粒数及腹壁撤退反射(AWR)评估动物肠道动力情况与内脏敏感性;采用Western blot法分析大鼠脑内及肠道内蛋白表达情况。结果:应激+肠道炎症组游泳不动时间抑制率为108.4%,远大于应激组的50.2%;应激+肠道炎症组的大理石掩埋颗粒数抑制率为211.6%,远大于应激组的112.3%。应激+肠道炎症组排便颗粒数增加的抑制率为131.4%,远大于肠道炎症组的97.1%;在内脏敏感性实验中,无论在60 mm Hg还是在80 mm Hg时,应激+肠道炎症组的AWR抑制率均大于肠道炎症组。应激+肠道炎症组大鼠海马及额叶皮层内脑源性神经营养因子(BDNF)、磷酸化环磷腺苷效应元件结合蛋白(p-CREB)表达降低较应激组更为显著;应激+肠道炎症组回肠及结肠内炎症因子IL-1β、IL-6表达升高均较肠道炎症组更为显著。结论:抑郁焦虑等情绪可通过调节肠内IL-1β及IL-6表达加重肠道功能紊乱,而肠道功能的紊乱又可通过调节脑内BDNF水平及降低环磷腺苷效应元件结合蛋白(CREB)的磷酸化加重抑郁焦虑等情绪,即抑郁焦虑情绪和肠道炎症两者之间具有一定程度的交互作用。
文摘肠道是营养物质消化吸收的主要部位,但易受外界环境刺激引起病理变化。动物肠道疾病的多发严重影响着动物的生长发育过程,增加动物的饲养成本,对养殖业的经济效益造成巨大冲击。虽然抗生素是缓解肠道疾病发生发展的有效策略,但因其耐药性以及药物残留等问题让人们不得不开发新的环境友好型替代产品。植物多糖广泛存在于自然界的植物中,具有高效、无毒副作用、无残留等特点。植物多糖作为绿色饲料添加剂,在保护动物肠道健康、提高动物生长性能方面发挥重要作用,其主要通过调控核因子-κB(nuclear factor kappaB,NF-κB)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)、Janus激酶/信号转导和转录激活因子(Janus kinase/signal transducer and activator of transcription,JAK/STAT)、转化生长因子-β(transforming growth factor-β,TGF-β)、磷脂酰肌醇-3-激酶/蛋白激酶B(phosphatidylinositol-3-kinase/protein kinase B,PI3K/Akt)等信号通路来充分发挥肠道各屏障的生理功能以及加强各屏障之间的相互联系,预防动物肠道疾病发生,调节肠道炎症水平,维持肠道微生物区系平衡,提升机体抗氧化能力,增强动物机体免疫性能,进而在一定程度上改善畜产品品质,提升动物创造的经济价值。作者综述了植物多糖对动物肠道的保护作用及其分子机制,并阐述了其在动物生产实践中的应用及取得的效果,旨在为植物多糖在动物生产中的应用提供参考。
