Abstract: Objective To investigate the roles of three Tiao-Bu Fei-Shen Traditional Chinese Medicine ( TCM) therapies in improving airway mucus hypersecretion in rats with stable chronic obstructive pulmonary disease ( COPD). Methods Ninety rats were divided randomly into nine groups: control (Control) group, model (COPD) group, Bu-Fei Jian-Pi Formula (BJF) group, Bu-Fei Yi-Shen Formula (BYF) group, Yi-Qi Zi-Shen Formula (YZF) group, ERK1 / 2 inhibitor (PD98059) group, Bu-Fei Jian-Pi combined with inhibitor (BJF + PD98059) group, Bu-Fei Yi-Shen combined with inhibitor (BYF + PD98059) group, and Yi-Qi Zi-Shen combined with inhibitor (YZF + PD98059) group. A rat model of COPD was established by exposing rats to cigarette smoke followed by repeated bacterial infection from weeks 1 ~8. From weeks 9 ~ 16, rats in the control and COPD groups were given 2 mL normal saline, rats in the BJF, BYF, and YZF groups were given the three Tiao-Bu Fei-Shen formulas by gavage, and rats in the PD98059, BJF + PD98059, BYF +PD98059, and YZF + PD98059 groups were given PD98059 by intraperitoneal injection for 7 days at the 16th week. Lung function tests were conducted after 16 weeks and lung tissue morphology, lung water content, inflammatory cell count in bronchoalveolar lavage fluid, and serum levels of inflammatory factors were also assessed. Goblet cell proportion was determined by Alcian blue-periodic acid-Schiff staining, and Muc5AC and Muc5B expression levels were detected by immunohistochemistry. mRNA expression levels of ERK1, ERK2, ENaC, CFTR, and AQP5 were detected by polymerase chain reaction and protein expression levels of ERK1 / 2 and P-ERK1 / 2 in lung tissue were determined by Western Blot. Results TV, MV, FVC, FEV0. 1 , FEV0. 1/ FVC were significantly decreased (P< 0. 01) in COPD rats compared with those in the control group. Lung pathology revealed alveolar disorder, massive fracture of the alveolar wall, and severe shrinkage / thickening of the airway wall accompanied by extensive infiltration of inflammatory cells. Lung tissue water content was significantly increased in COPD rats ( P< 0. 01), while the proportion of macrophages in BALF was significantly reduced (P< 0. 01) and the proportions of neutrophils and lymphocytes were significantly increased (P<0. 01). Serum levels of TNF-α and IL-1β were significantly increased in COPD rats ( P< 0. 05, P< 0. 01). The percentage of goblet cells and expression levels of Muc5AC and Muc5B in airway epithelial cells were significantly increased (P< 0. 01), mRNA expression levels of ERK1, ERK2, and ENaC in lung tissue were significantly elevated (P< 0. 01),while mRNA expression levels of CFTR and AQP5 were significantly decreased (P< 0. 01) in COPD rats compared with levels in the control group. The expression of P-ERK1 / 2, ERK1 / 2 in lung tissue was significantly increased (P< 0. 01) Rats in the treatment groups demonstrated improvements in the above indicators (P< 0. 05, P< 0. 01) compared with the COPD group, the groups receiving the three Tiao-Bu Fei-Shen formulas combined with PD98059 showing superior efficacy compared with the single treatment groups ( P< 0. 05, P< 0. 01). Conclusions The three tested Tiao-Bu Fei-Shen therapies can ameliorate airway mucus hypersecretion in COPD rats by inhibiting the ERK1 / 2 signaling pathway.

Abstract: Objective To establish a dynamic model of lipopolysaccharide-induced acute lung injury in mice based on the NLRP3 / Caspase-1/ gasdermin D (GSDMD) pyroptosis pathway, and observe the result ing lung injury at different time points. We aimed to identify the optimal time for modelling according to the injury at different time points and the expression of pyroptosis pathway-related proteins, to lay the foundation for animal models for subsequent experiments. Methods Fifty-four 6 ~ 8 weeks old male SPF BALB/ c mice were divided randomly into nine groups, including Con group and model groups at 1, 3, 6, 12, 18, 24, 48, and 72 h. Body weight and lung tissue were detected by general and pathological observations and semi-quantitative scoring, including lung index, lung water content, and wet and dry weight ratio. The white blood cell count and concentrations of tumor necrosis factor-α, interleukin ( IL)-6, IL-1β, IL-18, and BCA protein were detected in bronchoalveolar lavage fluid ( BALF). The classic pyroptosis pathway-related proteins NLRP3, pro-Caspase 1, Caspase 1, and GSDMD were detected by Western Blot. Results Body weight decreased in all experimental groups, with the most significant weight loss in the 24 and 48 h groups. Gross observation and pathological examination of lung tissue showed that the most severe lung injury occurred at 24 ~ 72 h, with significant differences between each group and the control group. The lung index, lung water content, and wet / dry weight ratio were also significantly increased at 24 ~ 72 h. White blood cells in BALF started to increase from 6 h after model initiation, 48 h can reach a peak, 72 h all keep increasing. IL-18 in BALF began to increase at 24 h and continued to increase at 72 h. The inflammatory factors tumor necrosis factor-α, IL-1β, IL-6 were highest at 6 h and significantly reduced at 48 h. Protein concentrations in BALF were significantly increased within 24, 48, and 72 h compared with those in the control group. The pyroptosis pathway proteins NLRP3, pro-Caspase-1, Caspase-1, and GSDMD were significantly enhanced in each time series, and channel protein expression was significantly enhanced at 24 ~ 72 h compared with that in the Con group. Conclusions Comprehensive analysis of experimental indicators, inflammatory factors, and pathway proteins at different times showed that the mechanism of pyroptosis was closely related to the occurrence and progression of acute lung injury. Expression of the pyroptosis pathway was most obvious and lung injury was most serious at 24 ~ 48 h. This study provides a model reference and experimental basis for subsequent studies of the specific mechanism and intervention targets of acute lung injury.

Abstract: Objective To construct models of viral transfection and hypoxia / reoxygenation induced cellular injury in adult mouse cardiomyocytes (AMCMs) isolated using a non-Langendorff method. Methods AMCMs were isolated,extracted, sedimented, and plated using a non-Langendorff method. The morphology and survival rate of the isolated cells were evaluated 2, 24, 48 and 72 h after plating, and their integrity was observed by immunofluorescence staining for αactinin. The isolated AMCMs were infected with adenoviruses carrying an RFP-expressing vector and fluorescence images were obtained at 36 and 48 h post-infection and used to calculate transfection efficiency. The cells were cultured under hypoxic conditions for 45 min, reoxygenated for 24 h, and then stained with propidium iodide (PI) to verify establishment of the hypoxia / reoxygenation injury model. Results The survival rates of AMCMs at 2, 24 and 48 h after plating were comparable, but survival was significantly reduced at 72 h. The integrity of the AMCMs was good and > 80% of the cells were transfected with adenovirus at 48 h. After hypoxia / reoxygenation treatment, 42% of cells were stained by PI, suggesting successful establishment of the AMCM injury model. Conclusions In this study, we developed a nonLangendorff method for the fast and easy isolation of AMCMs with high cell viability. The isolated cells can be efficiently infected with adenovirus and respond to hypoxia / reoxygenation injury. These findings provide a systematic method for isolating AMCMs and for applying gene modification and hypoxia / reoxygenation injury in these cells.

Abstract: Objective To establish a macrophage-specific KLF2 gene knockout mouse model, and explore the regulatory effect of KLF2 on the macrophage inflammatory response. Methods KLF2 flox / + mice were constructed using CRISPR/ Cas9 gene editing technology. Target genotype mice were obtained by breeding with Lyz2-Cre + / + mice and screening genotypes through polymerase chain reaction, and KLF2 knockout efficiency was verified using genotyping, qRTPCR, and Western Blot. Bone marrow-derived macrophages (BMDMs) were isolated and cultivated and mRNA levels of inflammation-related factors in lipopolysaccharide-induced BMDMs were detected. Results A KLF2 flox / flox / Lyz2-Cre+ mouse model was established. KLF2 mRNA and protein levels in mouse bone marrow and BMDMs were significantly lower in KLF2 knockout mice compared with the findings in control mice, while expression levels of KLF2 in the heart, liver, and kidney showed no significant changes compared with levels in the control group. There were no significant differences in body weight, diet, drinking water, and appearance between the two groups. The group receiving lipopolysaccharide stimulation showed significantly reduced interleukin (IL)-6 mRNA expression and significantly increased IL-1, iNOS, and CD86 mRNA expression in KLF2-deficient BMDMs compared with the control group. Conclusions We constructed a macrophage-specific KLF2 knockout mouse model, thus laying the foundation for further research on the regulatory effect and mechanism of macrophage KLF2 in clinical inflammatory-related diseases.

Abstract: Objective To investigate the effects of Jianpi Huatan Fang on lipid metabolism and expression levels of FOXO1 and PDK4 in rats with polycystic ovary syndrome (PCOS) and insulin resistance (IR). Methods Forty female rats were divided randomly into a blank control group (n = 10) and a model group (n = 30). A PCOS-IR rat model was established using a high-fat diet (8 weeks) combined with letrozole (added at weeks 4 ~ 8). Thirty successfully modeled rats were then divided randomly into a model control group, a Jianpi Huatan Fang group (11. 07 g / kg), and a metformin group (0. 2 g / kg) ( n = 10 rats per group). Drug intervention was given for 4 weeks. The general status, Traditional Chinese medicine syndrome score, and weight changes were observed in each group. Histopathological changes in the ovary were detected by hematoxylin and eosin staining. Fasting blood glucose and blood lipids were measured using a blood biochemical analyzer. Levels of sex hormones including follicle-stimulating hormone (FSH), luteinizing hormone (LH),testosterone(T), estradiol(E2 ), and insulin were determined by enzyme linked immunosorbent assay and changes in the expression of FOXO1 and PDK4 in the ovaries were determined by Western Blot and real-time fluorescence quantitative polymerase chain reaction. Results Rats in the model control group exhibited symptoms of spleen deficiency and phlegmdampness and showed significant weight gain, sex hormone disorders, polycystic ovarian changes, and dysregulation of glucose and lipid metabolism, compared with rats in the blank control group (P< 0. 01). In addition, weight increase was slower in rats in the Jianpi Huatan Fang group and the metformin group compared with that in the model control group, and follicle development was improved. Serum LH, T, LH/ FSH, fasting blood glucose, insulin, homeostatic model assessment for IR, cholesterol, triglycerides, and low-density lipoprotein cholesterol decreased, estradiol and FSH increased, and ovarian FOXO1 and PDK4 mRNA and protein expression levels were down regulated in the Jianpi Huatan Fang group compared with the findings in the model control group (P< 0. 05, P< 0. 01). Serum high-density lipoprotein cholesterol content was also increased, but the difference was not significant (P> 0. 05). Conclusions Jianpi Huatan Fang can effectively regulate sex hormone secretion, improve ovarian reproductive function, and regulate glucose and lipid metabolism in obese PCOS-IR rats, possibly via inhibiting the FOXO1 / PDK4 pathway.

Abstract: Objective To establish a palmitic acid (PA)-induced model of lipotoxic bone formation inhibition in zebrafish. Methods AB strain zebrafish embryos were divided randomly into a blank control group, PA group, and simvastatin (SIM) group. Embryos in the PA and SIM groups received PA from 3 days post-fertilization ( dpf), and embryos in the SIM group received SIM continuously for 4 days from 5 dpf. Establishment of the model was confirmed at 9 dpf by calcein staining, Nile red staining, triglyceride and total cholesterol content determination, and q-PCR. Results PA significantly decreased the number of vertebrae, promoted lipid accumulation, increased triglyceride and total cholesterol contents, promoted the expression of lipid-related genes PPARγ、 c / EBPα, and inhibited the expression of osteogenic genes ALP and RUNX2. SIM improved the inhibitory effect of PA on bone formation in zebrafish. Conclusions PA can successfully create a lipotoxic model of bone-formation inhibition, similar to the pathological process of osteoporosis, using a simple, sensitive, and controllable method. This model can then be used for drug screening for osteoporosis and related diseases.

Abstract: Objective Polymorphic microsatellite markers developed for Apodemus peninsulae can enrich its genetic data and lay a foundation for genetic quality control and gene mapping. Methods Microsatellite loci were screened based on the genome sequence of Apodemus peninsulae, and microsatellite primers were identified. The genetic diversity of the population was analyzed by multiplex PCR. Results Thirty microsatellite markers were successfully developed and evaluated using 60 samples of Apodemus peninsulae. A total of 152 alleles were detected, with an average of 5. 067 alleles per locus. The average observed heterozygosity was 0. 592. The average Shannon index was 1. 265. The average polymorphism information content was 0. 598. Conclusions Based on the microsatellite loci developed in this study, the genetic diversity of Apodemus peninsulae can be effectively analyzed, laying a foundation for establishing genetic quality standards and detection method.

Abstract: Objective To use metabolomics method to study the metabolic profiles of amino acids and lysophosphatidylcholine (LPC) in the serum of rats with nonalcoholic fatty liver disease (NAFLD), to identify biomarkers for NAFLD, and to speculate on the possible mechanism responsible for its occurrence. Methods NAFLD rats were prepared by feeding a high-fat diet and intraperitoneal injection of carbon tetrachloride. Levels of 15 LPCs and 18 amino acids in the serum were determined in control and NAFLD rats by liquid chromatography-mass spectrometry. Changes in serum LPC and amino acid metabolic profiles in NAFLD rats were analyzed by principal component analysis and orthogonal partial least squares discriminant analysis. Correlations between biomarkers and NAFLD were analyzed by Pearson’ s correlation analysis. Results The metabolic profiles of serum LPC and amino acids differed significantly between the NAFLD group and the control group and were completely distinct. LPC ( 20 ∶ 1), arginine, and glutamic acid had significant contributions to NAFLD and were identified as biomarkers. Furthermore, LPC ( 20 ∶ 1) and arginine were significantly correlated with serum biochemical indicators such as aspartate transaminase, alanine transaminase, low-density lipoprotein, and total bilirubin. Conclusions The metabolic profiles of serum LPC and amino acids may be closely related to NALFD.

Abstract: Objective To establish an animal model of lung adenoma in BALB/ c mice based on dynamic characterization by micro-computed tomography (CT). Methods Eighty female SPF-grade BALB/ c mice were divided randomly into four groups: model low dose group ( 1 mg / g urethane, iP, once), model medium dose group ( 1 mg / g urethane, ip, once a week, followed by 2 weeks), model high dose group (1 mg / g urethane, ip, once a week, followed by 4 weeks), and blank group (equal volume of saline). Growth of lung nodules in the mice was monitored regularly using Micro-CT. Three-dimensional images of the lungs were drawn using the Analyze 12. 0 system, and lung tissues were taken for histopathological examination (hematoxylin and eosin). Results Lung nodules with round high-density shadows were observed at week 11 in all model groups compared with the findings in the blank group. The rate of nodule formation increased with increasing modeling weeks, with rates of nodule formation in the model high, medium, and low dose groups of 93. 8%, 93. 8%, and 87. 5%, respectively, at week 21. Most mice had two to four, followed by one, and one to two nodules, respectively. The average maximum diameter of the lung nodules in the low dose group was significantly higher than the diameters in the medium- and high-dose groups (P< 0. 05), but there was no significant difference in lung nodule volume among the three groups. Regarding pathological type, hematoxylin and eosin staining revealed that the tumors in all the model groups were lung adenomas. Conclusions Lung adenomas were successfully induced in all urethane dose groups of mice and growth of the lung nodules could be characterized by micro-CT. The rate of nodule formation was highest in the medium dose group, which developed a moderate number of lung adenomas and provided a stable model, and was thus considered the most suitable model for the study of lung adenomas in mice.

Abstract: Objective To establish a liver-specific Rbp4 gene knockout mouse model and to explore the effect of liver Rbp4 gene deletion on glucose metabolism. Methods Cre-LoxP technology was used to construct a liver-specific Rbp4 gene knockout mouse model using C57 / BL6J and Alb-Cre mice. The genotype of the mice was identified by polymerase chain reaction and agarose gel electrophoresis. Ten 18 week old C57 / BL6J male mice were included in the WT group, 10 flox homozygous and Alb-Cre negative mice of the same age were included in the experimental control group(Rbp4 flox / flox: Cre-), and 10 flox homozygous and Alb-Cre positive mice of the same age were included in the experimental group (Rbp4 flox / flox: Cr e+). Expression levels of RBP4 protein and mRNA in the liver were verified by Western Blot and quantitative reverse transcription-polymerase chain reaction ( qRT-PCR), respectively, and expression levels of Rbp4 mRNA in other tissues were detected by qRT-PCR. Morphological changes in liver tissue were detected by hematoxylin and eosin staining. Blood glucose values were detected in mouse tail vein blood samples using a blood glucose meter, and glucose tolerance and insulin tolerance were determined. Expression levels of the liver glucose metabolism genes phosphoenolpyruvate carboxylase ( Pepck) and glucose-6-phosphatase ( G6pase) were detected by qRT-PCR. Results Liver-specific Rbp4 knockout mice were successfully bred and identified. RBP4 protein and mRNA levels were significantly decreased in the liver of Rbp4flox / flox: Cre + mice ( P< 0. 05), but there was no significant difference in the relative expression levels of Rbp4 mRNA in fat, kidney, pancreas, spleen, heart, or muscle tissues among the three groups (P>0. 05). Liver-specific Rbp4 knockout had no significant effect on liver morphology, glucose tolerance, or insulin tolerance (P> 0. 05). Pepck mRNA levels in the liver differed significantly among the three groups (P< 0. 05), and pairwise comparison showed that liver Pepck mRNA levels were significantly lower in Rbp4 flox / flox: Cre + mice compared with levels in Rbp4 flox / flox: Cre - mice (P< 0. 05). There was no significant difference in liver glucose-6-phosphatase (G6pase) mRNA expression among the three groups (P> 0. 05). Conclusions We successfully constructed a liver-specific Rbp4 knockout mouse model. Deletion of Rbp4 in the liver inhibited expression of Pepck mRNA in the liver, thus providing a basis for further exploration of the role of this gene in glucose metabolism in mice.

Abstract: Objective Utilizing transcriptomic sequencing, this study aimed to monitor the expression alterations of GIMAP8 and SEC14L5 throughout the progression of pulmonary fibrosis, thereby providing insights into the underlying mechanisms of its pathogenesis and evolution. Methods C57BL/ 6 male mice were assigned in a randomized manner to either the Silica or PBS group. The Silica group underwent non-exposed endotracheal intubation on days 0 and 14 with 50 μL 100 mg / mL silica suspension, while the control group received 50 μL phosphate-buffered saline solution. On day 28,lung function was detected and the mice were sacrificed, and lung morphology, fibrosis, and mRNA levels were observed. Results When contrasted with individuals in good health, a differential expression analysis of mRNA in patients with pneumoconiosis identified a total of 584 mRNAs with significant expression differences. Among these, the expression of 242 mRNA was observed to be markedly elevated, while that of 342 mRNA was found to be considerably diminished. The enrichment analysis indicated that the primarily affected mRNAs with altered expression were associated with pathways such as p53, nuclear factor-κB, tumor necrosis factor, AMP-activated protein kinase, and other signaling pathways. In the Silica mice, the alveolar structures were compromised, characterized by the presence of collagen fiber accumulation and the formation of fibrous masses. In contrast, the PBS mice maintained a normal pulmonary architecture. GIMAP8 expression was up-regulated whereas SEC14L5 expression was down-regulated in lung tissues in the Silica mice, and mice in the Silica group had poorer lung function. Conclusions The onset and progression of pulmonary fibrosis may be significantly influenced by GIMAP8 and SEC14L5 expression in patients with pneumoconiosis and in silicosis animal models. This association could serve as a foundational molecular insight, paving the way for the development of preventative and therapeutic strategies against these conditions.

Abstract: Objective To investigate the modeling of Henoch-Sch?nlein purpura nephritis based on data mining,and to provide a reference for the preparation of a standardized Henoch-Sch?nlein purpura nephritis animal model. Methods We searched the CNKI, Wanfang Data, VIP, China Biomedical Literature Database, and PubMed ChineseEnglish Database by computer to obtain studies of animal experiments relating to Henoch-Sch?nlein purpura nephritis in the past 20 years. The species, modeling method, dosage, dosing cycle, modeling standards, and detection indexes were screened manually, and a database was established by using Microsoft Excel 2021 software for statistical analysis. The association rules of high-frequency indicators were analyzed using SPSS Modeler 18. 0, and Cytoscape 3. 6. 1 was used to visually upgrade the association network diagram. Results A total of 106 articles that met the inclusion criteria were summarized. SD rats and KM mice were the mostly commonly used animal models of Henoch-Sch?nlein purpura nephritis and most studies used drug-induced models. Bovine serum albumin ( BSA) + lipopolysaccharide ( LPS ) + carbon tetrachloride(CCl 4 ) + castor oil, ovalbumin(OVA) + Freund’ s complete adjuvant, gliadin + Indian ink, and BSA + staphylococcal enterotoxin B(SEB) were used to produce the animal models, generally with cycles of 5 ~ 14 weeks. The standard of modeling was skin purpura and increased numbers of urine red blood cells. Proteinuria, glomerular mesangial hyperplasia in kidney tissue, and immune complex mainly composed of immunoglobulin A (IgA) deposited in small blood vessels indicated successful modeling. There were 36 medical indexes, including 23 indexes related to the kidney and urine and nine indexes related to blood. Among these, 10 indexes, such as 24 h urine protein quantification, interleukin, renal pathology, urine red blood cell count, IgA, circulating immune complex and creatinine were used in ≥ 10% of cases. Cluster analysis of high-frequency indicators showed that the comprehensive evaluation model of 24 h urinary protein quantification + interleukin + renal pathology + urinary red blood cell count + IgA was mostly used. Conclusions Most existing animal models of Henoch-Sch?nlein purpura nephritis have used male SD rats or female Kunming mice, and most models were induced by drugs. Among these, the method of stasis-heat syndrome combined with IgA nephropathy (diseasesyndrome combination method ) has the advantages of good repeatability and a high modeling rate, and may thus provide a reference for the selection of animal experimental models of Henoch-Sch?nlein purpura nephritis.

Abstract:Hemophilic arthritis (HA), caused by recurrent bleeding, can seriously affect patient quality of life and consumes extensive social and medical resources. There is thus a need to establish an animal model of HA for research; however, this is limited by ethical requirements. Here we review the recent literature and summarize research progress into animal models of HA at home and abroad, from the aspects of species selection, modeling method,histopathology, and imaging evaluation method. Species selection includes rodents such as mice, New Zealand rabbits, beagles, miniature pigs, and crab-eating macaques. Modeling method comprise gene knockout trauma models, gene knockout spontaneous models, and injection models. Among these, the gene knockout spontaneous model closely mimics the pathological process of spontaneous bleeding and concurrent arthritis in human HA, making it more relevant to human HA. However, due to high modeling costs, phenotypic instability, and low survival rates, this model is not the preferred choice for animal experimental studies. In contrast, gene knockout trauma models exhibit characteristics such as short modeling time, strong stability, and high success rates, thus being widely utilized in animal experimental research.Evaluation of HA models involves various imaging method including MRI, micro-CT, MSKUS / PD, in addition to various gross scoring method. By reviewing the progress of HA model research, more experimental evidence is provided for investigating the pathogenesis and validating the efficacy of HA treatments, thereby compensating for the lack of clinical data, particularly in the field of traditional Chinese medicine therapy.

Abstract:Population aging in China has led to an increase in the incidence of abdominal aortic aneurysm(AAA). AAA rupture is one of the most severe life-threatening diseases, with high mortality. The main histopathological features of AAA include elastin degradation, smooth muscle cell depletion, extracellular matrix digestion, and mural leukocyte accumulation. Clinically, drug therapy is still lacking, and open / endovascular repair remains the most effective treatment strategy for AAA management. Notably however, the detailed molecular mechanism of AAA remains unclear,representing an important bottleneck affecting the development of potential drug targets. Animal models are the most powerful tools for clarifying the pathogenesis of AAA, and although some medium-to-large laboratory animal models (e. g. ,rabbits, guinea pigs, dogs, pigs) have been established for AAA studies, rodent models (mice and rats) are still the main models used in this field. Current method of inducing AAA include intra-infrarenal aortic infusion of elastase, subcutaneous infusion of angiotensin Ⅱ, periaortic calcium chloride painting, and decellularized aortic xenografting; however, AAA tends to stabilize in most models after ceasing pre-induced stimulation (medical or surgical), and there remains a need for ideal animal models that maintain continuous aortic dilation and even rupture. AAA animal models are helpful for elucidating the pathogenesis of AAA, screening new drug targets, and promoting clinical translation. This review aims to discuss the application of current AAA modeling method and their translational relevance.

Abstract:The intestine is the largest immune and metabolic site in the body and is thus important for animal health. The integrity of the mucosal barrier and function are fundamental factors protecting the health of the intestine. Stress has been reported to have profound effects on the gastrointestinal tract, including altering gut permeability, the intestinal barrier, and homeostasis. Tryptophan is a functional essential amino acid that alters the gut microbiota and regulates intestine structural and functional change, thus contributing to host physiology and metabolism. Changes in tryptophan metabolism and its metabolites in brain and intestinal tissues during stress suggest that tryptophan may play an important role in the stress response. We therefore review the literature on the mechanisms underlying stress-related diseases and the role of tryptophan metabolism in the regulation of gut homeostasis, with particular focus on functional bowel disorders and their relationship to stress, to provide a theoretical foundation for targeting tryptophan in stress-related intestine diseases.