BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling p...BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.展开更多
功能性消化不良(FD)的胃肠动力障碍与Cajal间质细胞(ICC)网络损伤密切相关。文章系统阐述干细胞因子(SCF)/c-kit信号通路在FD发病中的核心作用,提出柴桂和胃方通过三重机制修复ICC网络:1) 柴胡皂苷激活c-kit受体促ICC增殖;2) 桂枝成分...功能性消化不良(FD)的胃肠动力障碍与Cajal间质细胞(ICC)网络损伤密切相关。文章系统阐述干细胞因子(SCF)/c-kit信号通路在FD发病中的核心作用,提出柴桂和胃方通过三重机制修复ICC网络:1) 柴胡皂苷激活c-kit受体促ICC增殖;2) 桂枝成分抑制肿瘤坏死因子-α (TNF-α)改善炎症微环境;3) 白芍苷调节5-羟色胺(5-HT)信号恢复脑肠轴平衡。基于“肝郁脾虚-ICC功能障碍”病机对应理论,构建中药复方多靶点修复胃肠起搏网络的新假说,为中西医结合治疗提供理论依据。Gastrointestinal dyskinesia in functional dyspepsia (FD) is closely related to the damage of Cajal interstitial cell (ICC) network. In this paper, the central role of the stem cell factor (SCF)/c-kit signaling pathway in the pathogenesis of FD was systematically elucidated, and it was proposed that the Chai Gui Hewei Decoction repaired the ICC network through a three-fold mechanism: 1) Bupleurum saponin activated the c-kit receptor to promote the proliferation of ICC;2) Cinnamomum cassiae ingredient inhibited the tumor necrosis factor-α (TNF-α) to improve the inflammation microenvironment;3) Paeonia lactiflora glucoside regulates 5-hydroxytryptamine (5-HT) signaling to restore the balance of brain-gut axis. Based on the theory of “liver depression and spleen deficiency-ICC dysfunction”, a new hypothesis of multi-target repair of gastrointestinal pacing network by traditional Chinese herbal medicine compound was constructed, which provides a theoretical basis for the combination of Chinese and Western medicine.展开更多
胃肠动力障碍性疾病(disorders of gastrointestinal motility,DGIM)是指因胃肠动力失常引起的以消化道症状为主要临床表现的疾病。DGIM的发病率有逐年升高的趋势,降低人们生活质量的同时,还增加了社会的医疗支出。DGIM的发病机制尚未...胃肠动力障碍性疾病(disorders of gastrointestinal motility,DGIM)是指因胃肠动力失常引起的以消化道症状为主要临床表现的疾病。DGIM的发病率有逐年升高的趋势,降低人们生活质量的同时,还增加了社会的医疗支出。DGIM的发病机制尚未完全阐明,多项研究表明其发生发展与胃肠道动力异常关系密切。胃肠动力与胃肠道Cajal间质细胞(ICC)密切相关。ICC是胃肠道产生慢波运动的特殊细胞,ICC数量和形态的保持又与SCF/c-kit信号通路密切相关。近年来的研究表明,SCF/c-kit信号通路的异常改变可导致DGIM的发生。目前,DGIM的西医治疗主要为促动力及抑酸等对症治疗,在一定程度上能够缓解DGIM的症状,但常伴有不良反应,使药物的应用范围受限,而大量研究证实,中药、中药单体或成分、复方、中医外治法均可通过调节SCF/c-kit信号通路,有效改善胃肠动力的同时,不良反应较小。虽然中医药通过调控SCF/c-kit信号通路干预DGIM具有西医难以取代的独特优势,但目前中医药调控SCF/c-kit信号通路治疗DGIM系统综述仍较少。文章就SCF/c-kit信号通路与DGIM之间的相关性、中医药调控SCF/c-kit信号通路干预DGIM的作用机制进行系统性总结,旨在为临床治疗DGIM及新药研发提供新思考。展开更多
Background:Huoxue Tongjiang decoction(HXTJD)is an effective prescription for treating reflux esophagitis(RE).We investigated the effects of HXTJD on esophageal motility and mucosal inflammation in a rat RE model.Metho...Background:Huoxue Tongjiang decoction(HXTJD)is an effective prescription for treating reflux esophagitis(RE).We investigated the effects of HXTJD on esophageal motility and mucosal inflammation in a rat RE model.Methods:Chemical composition of HXTJD was analyzed by ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry(MS).The change rates of mean contraction tension forces,mean amplitudes,and mean frequencies for the lower esophageal sphincter(LES)were recorded using the isolated tissue bath system,mechanical tension transducer,and PowerLab physiological recorder.After weighing the stomach,the phenol red labeling method was used to measure the gastric emptying rate.The LES ultrastructure was observed through transmission electron microscopy.Immunofluorescence and western blotting were used to detect the number of interstitial cells of Cajal(ICC)and the expression levels of c-kit protein,connexin43(Cx43),and stem cell factor(SCF).Flow cytometric analysis and enzyme-linked immunosorbent assay were conducted to detect the percentages of T helper 17(Th17)cells and regulatory T(Treg)cells and the serum concentrations of interleukin 6(IL-6),interleukin 17(IL-17),and interleukin 10(IL-10)in the rats.Results:We identified 28 chemical constituents in HXTJD.Regarding esophageal motility,we revealed that HXTJD increased the mean contraction tension forces,mean amplitudes,and mean frequency change rate of LES and the gastric emptying rate;decreased stomach weight;and improved the LES ultrastructure.Additionally,HXTJD increased the number of ICC-positive cells,and c-kit,Cx43,and SCF expression levels.Regarding esophageal inflammation,HXTJD significantly decreased the percentage of Th17 cells,and IL-6 and IL-17 concentrations,and increased the percentage of Treg cells and IL-10 concentration.Conclusion:HXTJD was found to be efficacious in the rat RE model.It may promote esophageal motility and alleviate the inflammatory response by activating the SCF/c-kit/ICC pathway and regulating the Th17/Treg cell balance.展开更多
文摘BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.
文摘功能性消化不良(FD)的胃肠动力障碍与Cajal间质细胞(ICC)网络损伤密切相关。文章系统阐述干细胞因子(SCF)/c-kit信号通路在FD发病中的核心作用,提出柴桂和胃方通过三重机制修复ICC网络:1) 柴胡皂苷激活c-kit受体促ICC增殖;2) 桂枝成分抑制肿瘤坏死因子-α (TNF-α)改善炎症微环境;3) 白芍苷调节5-羟色胺(5-HT)信号恢复脑肠轴平衡。基于“肝郁脾虚-ICC功能障碍”病机对应理论,构建中药复方多靶点修复胃肠起搏网络的新假说,为中西医结合治疗提供理论依据。Gastrointestinal dyskinesia in functional dyspepsia (FD) is closely related to the damage of Cajal interstitial cell (ICC) network. In this paper, the central role of the stem cell factor (SCF)/c-kit signaling pathway in the pathogenesis of FD was systematically elucidated, and it was proposed that the Chai Gui Hewei Decoction repaired the ICC network through a three-fold mechanism: 1) Bupleurum saponin activated the c-kit receptor to promote the proliferation of ICC;2) Cinnamomum cassiae ingredient inhibited the tumor necrosis factor-α (TNF-α) to improve the inflammation microenvironment;3) Paeonia lactiflora glucoside regulates 5-hydroxytryptamine (5-HT) signaling to restore the balance of brain-gut axis. Based on the theory of “liver depression and spleen deficiency-ICC dysfunction”, a new hypothesis of multi-target repair of gastrointestinal pacing network by traditional Chinese herbal medicine compound was constructed, which provides a theoretical basis for the combination of Chinese and Western medicine.
文摘胃肠动力障碍性疾病(disorders of gastrointestinal motility,DGIM)是指因胃肠动力失常引起的以消化道症状为主要临床表现的疾病。DGIM的发病率有逐年升高的趋势,降低人们生活质量的同时,还增加了社会的医疗支出。DGIM的发病机制尚未完全阐明,多项研究表明其发生发展与胃肠道动力异常关系密切。胃肠动力与胃肠道Cajal间质细胞(ICC)密切相关。ICC是胃肠道产生慢波运动的特殊细胞,ICC数量和形态的保持又与SCF/c-kit信号通路密切相关。近年来的研究表明,SCF/c-kit信号通路的异常改变可导致DGIM的发生。目前,DGIM的西医治疗主要为促动力及抑酸等对症治疗,在一定程度上能够缓解DGIM的症状,但常伴有不良反应,使药物的应用范围受限,而大量研究证实,中药、中药单体或成分、复方、中医外治法均可通过调节SCF/c-kit信号通路,有效改善胃肠动力的同时,不良反应较小。虽然中医药通过调控SCF/c-kit信号通路干预DGIM具有西医难以取代的独特优势,但目前中医药调控SCF/c-kit信号通路治疗DGIM系统综述仍较少。文章就SCF/c-kit信号通路与DGIM之间的相关性、中医药调控SCF/c-kit信号通路干预DGIM的作用机制进行系统性总结,旨在为临床治疗DGIM及新药研发提供新思考。
基金supported by the National Natural Science Foundation of China(No.81573737 and 82074213)the science foundation of Tianjin Municipal Health Bureau(No.2023169 and 2021045)the Tianjin Municipal Health Commission Science and Technology Project(No.TJWJ2022QN057).
文摘Background:Huoxue Tongjiang decoction(HXTJD)is an effective prescription for treating reflux esophagitis(RE).We investigated the effects of HXTJD on esophageal motility and mucosal inflammation in a rat RE model.Methods:Chemical composition of HXTJD was analyzed by ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry(MS).The change rates of mean contraction tension forces,mean amplitudes,and mean frequencies for the lower esophageal sphincter(LES)were recorded using the isolated tissue bath system,mechanical tension transducer,and PowerLab physiological recorder.After weighing the stomach,the phenol red labeling method was used to measure the gastric emptying rate.The LES ultrastructure was observed through transmission electron microscopy.Immunofluorescence and western blotting were used to detect the number of interstitial cells of Cajal(ICC)and the expression levels of c-kit protein,connexin43(Cx43),and stem cell factor(SCF).Flow cytometric analysis and enzyme-linked immunosorbent assay were conducted to detect the percentages of T helper 17(Th17)cells and regulatory T(Treg)cells and the serum concentrations of interleukin 6(IL-6),interleukin 17(IL-17),and interleukin 10(IL-10)in the rats.Results:We identified 28 chemical constituents in HXTJD.Regarding esophageal motility,we revealed that HXTJD increased the mean contraction tension forces,mean amplitudes,and mean frequency change rate of LES and the gastric emptying rate;decreased stomach weight;and improved the LES ultrastructure.Additionally,HXTJD increased the number of ICC-positive cells,and c-kit,Cx43,and SCF expression levels.Regarding esophageal inflammation,HXTJD significantly decreased the percentage of Th17 cells,and IL-6 and IL-17 concentrations,and increased the percentage of Treg cells and IL-10 concentration.Conclusion:HXTJD was found to be efficacious in the rat RE model.It may promote esophageal motility and alleviate the inflammatory response by activating the SCF/c-kit/ICC pathway and regulating the Th17/Treg cell balance.
