Seroprevalence of Fusobacterium varium in ulcerative colitis patients in Japan

The etiology of ulcerative colitis (UC) is unknown, while an exacerbating factor of this disease is associated with infectious agents. Recently, Fusobacterium varium has been found in the mucosa of a significant number of patients with UC. The aim of this study was to estimate the prevalence of F. varium infection based on serology, evaluate the relationship between F. varium seropositivity and UC, and determine the clinical characteristics of infected UC individuals. Seropositive patients were determined by immunoblotting with F. varium ATCC 8501 antigen. We also identified cross-reactive protein spots by peptide mass mapping analysis. These protein spots showed putative caseinolytic protease protein, putative translation elongation factor G, and putative enolase. Immunoblotting with F. varium antigen revealed signals with sera from 45 (40.2%) of the 112 UC patients and 20 (15.6%) of the 128 healthy controls, respectively ( P <0.01). In terms of disease activity, seropositive UC patients were more likely to have clinically severe disease than seronegative UC patients. Disease location in seropositive patients was more extensive than the seronegative patients. In conclusion, F. varium is a predominant infection in the UC population and is a potential pathogen of UC.     

Serum paraoxonase 1 activity and malondialdehyde levels in patients with ulcerative colitis

This study was designed to evaluate the oxidative and antioxidative status in patients with ulcerative colitis by detecting antioxidant enzyme paraoxonase 1 activity together with the level of a well-known marker of oxidative stress, malondialdehyde. Serum paraoxonase 1 activity and malondialdehyde levels were analysed in 30 patients with ulcerative colitis and 30 controls using a spectrophotometric method; correlation analysis was made between these variables. Serum malondialdehyde levels were higher in the ulcerative colitis group (median: 2.5, range: 0.5-9.4 nmol ml(-1)) than among the controls (median:1.1, range: 0.5-2.3 nmol ml(-1); p < 0.001) whereas paraoxonase 1 activities were lower in the ulcerative colitis group (median: 158.4, range: 61.6-264.1 U l(-1)) than in the control group (median: 233.3, range: 114.4-431.0 U l(-1); p < 0.001). There was no correlation between serum malondialdehyde level, paraoxonase 1 activity and disease activity. (1) Increased reactive oxygen metabolites levels in ulcerative colitis may result in a pro-oxidation environment, which in turn could result in decreased antioxidant paraoxonase 1 activity and increased malondialdehyde levels, (2) increased cytokines may be a possible cause of decreased paraoxonase 1 activity and (3) decreased serum paraoxonase 1 activity may be a part of an inflammatory response.     

Colonic vasoactive intestinal polypeptide in ulcerative colitis

Vasoactive intestinal polypeptide (VIP) is a 28 amino acid peptide which is localised in both the central and peripheral nervous system. In the human colon VIP is found in all layers and the highest concentrations have been found in the myenteric plexus. It is known that VIP has various effects on intestinal functions: i) it is a potent stimulant of mucosal water and electrolyte secretion: ii) it is involved in the peristaltic reflex: and iii) plays an inhibitory role on immune cell function. Based on these biological effects it has been hypothesized that the intestinal mucosal immune system and inflammation may be influenced by alterations in the tissue concentrations of VIP. Some authors have demonstrated no changes in the VIP colonic content of patients with ulcerative colitis, whereas others have demonstrated a reduction. Our results, using specific radioimmunoassay, showed that there is a significant decrease of VIP in both rectal and colonic mucosa of patients with ulcerative colitis as compared to controls. The VIP decrease is selective since substance P and calcitonin gene-related peptide were unchanged in the mucosal tissue of ulcerative colitis patients and furthermore the VIP alteration is correlated to the degree of mucosal inflammation. These findings suggest that the reduction of VIP mucosal content, even if it represents a non-specific event, could influence local inflammatory response and the activity of the disease.     

New molecular mechanisms of the unexpectedly complex role of VEGF in ulcerative colitis

The effects of VEGF on endothelial cells are mediated by different intracellular signaling cascades (e.g., Erk1/2, Akt, Src). VEGF plays a recently recognized role in ulcerative colitis (UC) pathogenesis, mostly by increasing vascular permeability and promoting the infiltration of inflammatory cells. We hypothesized that the excessive activation of signal transduction pathways, which is responsible for VEGF/VEGFR-2-mediated endothelial permeability (Src, Akt), is a new element in the pathogenesis of chronic UC. We demonstrated increased expression of pro-angiogenic growth factor VEGF and its receptor VEGFR-2 in colonic tissue during acute 6% iodoacetamide-induced UC in rats and chronic spontaneously developed UC in IL-10 knockout mice (IL-10 KO). Development of acute 6% iodoacetamide-induced UC in rats was accompanied by activation of Erk1/2 and Src kinase, while expression of total proteins Erk1/2 and Src was unchanged. During chronic colitis phosphorylation (i.e., activation) of Erk1/2 was significantly decreased in IL-10 KO mice vs. wild-type mice. Levels of total Erk1/2 proteins were unchanged, but the expression of total Src protein as well as its phosphorylated form was significantly increased in IL-10 KO vs. wild-type mice. There were no changes in total Akt proteins, while levels of activated Akt (pAkt) were slightly increased in IL-10 KO vs. wild-type mice. We conclude that VEGF/VEGFR-2-associated signal transduction pathways, that mediate increased vascular permeability (Src, Akt), might play a central role in perpetuation of chronic experimental UC.     

Altered oligosaccharide expression in ulcerative colitis with increasing grades of inflammation

Ulcerative colitis is an idiopathic chronic inflammatory condition of the large bowel associated with åbnormalities of mucin synthesis and secretion. In the present study, glycans were identified in 45 formalin-fixed, paraffin-embedded tissue samples from patients with ulcerative colitis. The tissue samples represented a spectrum of inflammation from chronic quiescent disease to severe inflammation. Thirteen biotinylated lectins, directed against a range of sialyl, fucosyl andN-acetylgalactosaminyl sequences, were applied using an avidin-peroxidase revealing system. The results were assessed semiquantitatively for a number of cellular sites. The expression of all sialyl sequences was increased in absorptive cells and in goblet cells and the expression of 2–6-linked sialyl sequences was enhanced in proportion to the degree of inflammation, while 2–3-linked sialyl sequences were diminished in more severe inflammation. The binding ofN-acetylgalactosaminyl-directed lectins was increased in the Golgi apparatus, while there was a reduction in the expression of -fucosyl sequences in severe degrees of inflammation. This suggests that there is an increased biosynthetic rate for sialyl residues in all stages of disease with a reduction in 2–3-linked sialyl and fucosyl sequences in severe inflammation, and a shift from storedN-acetylgalactosaminyl sequences in goblet cells to an earlier form in the Golgi apparatus. The changes in sialyl sequences are a feature of ulcerative colitis even in quiescent disease and may be related to its aetiology and early pathogenesis, while most of the other changes reflect the severity of the disease and are probably part of its later pathogenesis or of induced reactive changes.     

Circulating memory B cells and plasmablasts are associated with the levels of serum immunoglobulin in patients with ulcerative colitis

Humoural immunity is crucial for the pathogenesis of ulcerative colitis (UC), but the precise perturbation of B cell immunity is poorly understood. This study is aimed at evaluating the numbers of different subsets of circulating memory B cells, plasmablasts, and the levels of serum immunoglobulin in UC patients. Total of 23 patients with active UC and 14 healthy controls (HC) were examined for the numbers of different subsets of circulating memory B cells and plasmablasts before and after treatment with mesalazine for 8–12 weeks by flow cytometry. Disease activity was evaluated by the Mayo clinic score. The levels of serum immunoglobulin, C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured in individual subjects. In comparison with that in HC, significantly reduced numbers of IgG⁺ IgD^? CD27⁺ CD19⁺ memory B cells, increased numbers of CD20^? CD19⁺ plasmablast subsets, and higher serum IgG levels were detected in UC patients. The concentrations of serum IgG, the numbers of CD138⁺ CD38⁺ CD20^? CD19⁺, and IgG⁺ CD38⁺ CD20^? CD19⁺ plasmablasts were negatively associated with the numbers of IgG⁺ IgD^? CD27⁺ CD19⁺ memory B cells. Furthermore, the values of Mayo clinic score, CRP, or ESR in UC patients were negatively correlated with the numbers of IgG⁺ IgD^? CD27⁺ CD19⁺ memory B cells, while positively correlated with the serum IgG levels and the numbers of plasmablast subsets. Following treatment with mesalazine, the numbers of circulating IgG⁺ IgD^? CD27⁺ CD19⁺ memory B cells were significantly increased, while the numbers of CD138⁺ CD38⁺ CD20^? CD19⁺ and IgG⁺ CD38⁺ CD20^? CD19⁺ plasmablasts were reduced in UC patients. These decreased IgG⁺ IgD^? CD27⁺ CD19⁺ memory B cells and increased plasmablasts may be involved in the pathogenic process of UC.     

Molecular mimicry may contribute to pathogenesis of ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with mucosal inflammation and ulceration of the colon. There seems to be no single etiological factor responsible for the onset of the disease. Autoimmunity has been emphasized in the pathogenesis of UC. Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) are common in UC, and recently two major species of proteins immunoreactive to pANCA were detected in bacteria from the anaerobic libraries. This implicates colonic bacterial protein as a possible trigger for the disease-associated immune response. Autoantibodies and T-cell response against human tropomyosin isoform 5 (hTM5), an isoform predominantly expressed in colon epithelial cells, were demonstrated in patients with UC but not in Crohn's colitis. We identified two bacterial protein sequences in NCBI database that have regions of significant sequence homology with hTM5. Our hypothesis is that molecular mimicry may be responsible for the pathogenesis of UC.     

Association of vitamin D receptor gene polymorphisms with the susceptibility to ulcerative colitis in patients from Southeast China

Abstract

The association studies from different ethnic groups showed that vitamin D receptor (VDR) gene polymorphisms might be connected with the susceptibility to ulcerative colitis (UC); however, the conclusions were less consistent. Our study aimed to analyze the associations of UC with common mutations of VDR in Chinese patients. A total of 382 UC patients and 489 healthy controls were recruited. The genotypes of VDR FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) were examined by SNaPshot assays. Haplotype analysis was performed in all study subjects. After Bonferroni correction, the mutant alleles and genotypes of VDR FokI, BsmI, ApaI and TaqI did not statistically differ between UC patients and the controls (all p?>?0.0125). However, the mutant allele C and genotype TC?+?CC of FokI gene were significantly increased in patients with mild and moderate UC compared to those with severe UC (C allele: 54.1% versus 39.3%, OR?=?1.83, 95% CI: 1.21–2.75, p?=?0.004; TC?+?CC genotype: 81.6% versus 57.1%, OR?=?3.32, 95% CI: 1.83–6.06, p?<?0.001, respectively). Haplotype analysis showed that the VDR BsmI, ApaI and TaqI polymorphic loci were in a strong linkage disequilibrium. Furthermore, the frequency of AAC haplotype was statistically lower in UC patients than that in the controls (3.8 versus 5.9%, OR?=?0.63, 95% CI: 0.39–1.01, p?=?0.039). In conclusion, the mutation of FokI gene influenced severity of the disease in UC patients. Moreover, the AAC haplotype formed by the VDR BsmI, ApaI and TaqI gene might engender a reduced risk of UC attack.     

Inflammation-associated DNA methylation patterns in epithelium of ulcerative colitis

Aberrant DNA methylation patterns have been reported in inflamed tissues and may play a role in disease. We studied DNA methylation and gene expression profiles of purified intestinal epithelial cells from ulcerative colitis patients, comparing inflamed and non-inflamed areas of the colon. We identified 577 differentially methylated sites (false discovery rate <0.2) mapping to 210 genes. From gene expression data from the same epithelial cells, we identified 62 differentially expressed genes with increased expression in the presence of inflammation at prostate cancer susceptibility genes PRAC1 and PRAC2. Four genes showed inverse correlation between methylation and gene expression; ROR1, GXYLT2, FOXA2, and, notably, RARB, a gene previously identified as a tumor suppressor in colorectal adenocarcinoma as well as breast, lung and prostate cancer. We highlight targeted and specific patterns of DNA methylation and gene expression in epithelial cells from inflamed colon, while challenging the importance of epithelial cells in the pathogenesis of chronic inflammation.     

溃疡性结肠炎患者肠道菌群分布的研究现状

溃疡性结肠炎(Ulcerative colitis,UC)的发病被认为是宿主遗传易感性、黏膜免疫与肠道菌群共同作用的结果。许多临床研究显示,与正常人相比,UC患者存在不同程度的菌群失调。艰难梭菌、致病性大肠埃希菌等致病微生物被怀疑与UC的发病相关,但目前还未找到充分证据证明它们与UC患者肠道炎症间的因果关系。就UC患者肠道菌群分布的研究现状、肠道菌群检测方法及未来研究进展进行了阐述。     

Oxidative stress in ulcerative colitis: an old concept but a new concern

Abstract

Ulcerative colitis is an idiopathic, chronic and relapsing inflammatory bowel disease, which elicits the risk of colorectal cancer, the third most common malignancy in humans. It has been known for a long time that oxidative stress is a major pathogenic factor in the inflamed tissue that can pave the way towards DNA damage and carcinogenesis. However, the DNA damage produced due to oxidative stress in the inflamed tissue is not limited to the local site but extends globally, thereby augmenting the risk of global carcinogenesis. Targeting oxidative stress may provide an exciting avenue to combat inflammation-associated local as well as global DNA damage and the subsequent carcinogenesis. The present review portrays the role of oxidative stress in the pathogenesis of ulcerative colitis and the associated local as well as global DNA damage, which may lead to carcinogenesis.     

Dietary glycated protein modulates the colonic microbiota towards a more detrimental composition in ulcerative colitis patients and non-ulcerative colitis subjects

Aim:  To investigate the effect of native, heated and glycated bovine serum albumin (BSA) on the ulcerative colitis (UC) and non-UC colonic microbiota in vitro .
Methods and Results:  Continuous flow culture (CFC) models of the human colonic microbiota inoculated with faeces from UC and non-UC volunteers were maintained on BSA as growth substrate. Changes in bacterial populations and short-chain fatty acids were determined. UC and non-UC microbiota differed significantly in microbial populations, with elevated numbers of sulfate-reducing bacteria (SRB) and clostridia in the microbiota from UC patients. Compared with native BSA, glycated BSA modulated the gut microbiota of UC patients in vitro towards a more detrimental community structure with significant increases in putatively harmful bacteria (clostridia, bacteroides and SRB; P  < 0·009) and decreases in dominant and putatively beneficial bacterial groups (eubacteria and bifidobacteria; P  < 0·0004). The levels of beneficial short-chain fatty acids were significantly decreased by heated or glycated BSA, but were increased significantly by native BSA.
Conclusion:  The UC colonic microbiota maintained in CFC was significantly modified by glycated BSA.
Significance and Impact of the Study:  Results suggest that dietary glycated protein may impact upon the composition and activity of the colonic microbiota, an important environmental variable in UC.     

鼠衣原体改善DSS诱导的小鼠溃疡性结肠炎的作用研究

【目的】探讨鼠衣原体(Chlamydia muridarum)对小鼠溃疡性结肠炎的作用。【方法】取15只雌性C57BL/6J小鼠随机分为3组,每组5只动物,分别为空白对照组(Control)、肠炎模型组(DSS)、实验组(CM+DSS)。选取CM+DSS组小鼠予以2×10⁵ IFU的鼠衣原体灌胃处理,并在其感染后第29天开始,给予DSS组和CM+DSS组的小鼠2%DSS饮水,持续5d,每天监测小鼠体重和肠炎疾病评分,实验结束后检测小鼠结肠长度和结肠组织炎性改变。【结果】肠炎模型组的小鼠均表现出典型的肠炎症状(包括体重减轻、肠炎疾病评分、结肠长度和组织炎性改变);而经鼠衣原体预处理的小鼠(CM+DSS组)肠炎症状显著减轻,表现在肠炎疾病评分降低,体重和结肠长度有所恢复,肠组织炎性损伤减轻。【结论】鼠衣原体对DSS诱导的小鼠溃疡性结肠炎具有改善作用。     

Colonic mucins in ulcerative colitis: evidence for loss of sulfation

Colonic tissue obtained at surgery from control individuals and patients with ulcerative colitis was used to isolate mucins and to prepare mucin glycopolypeptides by pronase digestion. These were compared with mucins labelled with [³⁵S] sulfate and [³H]-glucosamine after organ culture tissue samples from the same patients. A significant loss of mucin sulfation was detected in the colitis patients by both metabolic labelling and chemical analysis of the glycopolypeptides. A change in the size distribution of purified mucin oligosaccharides fractionated on BioGel P6 after release by -elimination was seen in both radiolabelled and non-labelled colitis mucins compared with controls. Amino acid analysis of the glycopolypeptides showed a close similarity to the expected ratio of serine:threonine:proline for MUC2 and did not vary between control and colitis groups. Analysis of the mucins confirmed >90% purity in the labelling experiments, characteristic behaviour on density gradient centrifugation and agarose gel electrophoresis in control and ulcerative colitis groups and differences in sulfation and turnover at various sites in the normal colon.Abbreviations WGA wheat germ agglutinin - UC ulcerative colitis - HRP horseradish peroxidase     

白藜芦醇对小鼠溃疡性结肠炎的影响*

目的:研究白藜芦醇通过调节Wnt/β-catenin信号通路抗溃疡性结肠炎的作用机制。方法:①葡聚糖硫酸钠盐(DSS)诱发溃疡性结肠炎实验:28只C57BL/6小鼠随机分为4组(n=7):control组、 DSS组、DSS+白藜芦醇(DSS+Res)组和Res组。实验周期为3周,小鼠饮用DSS水诱导溃疡性结肠炎并给予白藜芦醇灌胃。实验期间每天称小鼠体重并观察小鼠活动和粪便情况。处理结束后,安乐死小鼠,取小鼠脾脏称重,取小鼠结肠测量长度。苏木精-伊红染色法(H&E)染色观察小鼠结肠组织病理改变;实时荧光定量PCR(qPCR)检测小鼠结肠组织miRNA-31的表达;Western Blot检测小鼠结肠组织β-catenin、Cyclin D1蛋白的表达。②离体实验:以10 mg/ml浓度的白藜芦醇处理HCT 116细胞,检测HCT 116细胞β-catenin、低密度脂蛋白受体相关蛋白6(LRP-6)、卷曲蛋白3(FZD3)、c-Myc蛋白的表达;HCT 116细胞转染miRNA-31 mimic和inhibitor,检测β-catenin蛋白的表达。结果:①DSS组小鼠实验期间体重下降明显,精神萎靡,活动减少,出现血便;处理结束后小鼠的结肠长度缩短,脾脏增大。而给予白藜芦醇后小鼠的以上情况得到改善。②白藜芦醇抑制了溃疡性结肠炎小鼠结肠组织miRNA-31的表达及β-catenin、Cyclin D1蛋白的表达。③白藜芦醇下调HCT 116细胞β-catenin、LRP-6、FZD3、c-Myc蛋白的表达。转染miRNA-31 inhibitor后,HCT 116细胞中β-catenin蛋白表达减少。结论:白藜芦醇能够抑制DSS诱导的小鼠溃疡性结肠炎,这种作用与下调Wnt信号通路有关,其对Wnt 信号的下调作用与miRNA-31有关。     

Mast cells in ulcerative colitis

The changes in the number and ultrastruture of mast cells were studied in 37 colonoscopical biopsies from patients with ulcerative colitis. Changes in the active stage of the disease and during remission were compared. Cell counts were performed on semithin sections stained with Giemsa after osmium tetroxide fixation. This method overcome the uncertain staining found after formalin fixation. Accumulation of mast cells accompanied by intense degranulation was found to be significant in the active stage of the disease. Two forms of degranulation were observed: discharge of the individual granules and protrusion and detachment of the cytoplasmic processes containing granules. The latter was a sign of rapid degranulation, as described earlier in animal experiments. Mast cells were closely associated with capillary blood vessels, Schwann cells, neural fibres, myofibroblasts and collagenous fibres, and were also present between epithelial cells. It is assumed that close topographic contact may also imply a functional correlation.     

Phellodendrine promotes autophagy by regulating the AMPK/mTOR pathway and treats ulcerative colitis

To investigate the therapeutic effects of phellodendrine in ulcerative colitis (UC) through the AMPK/mTOR pathway. Volunteers were recruited to observe the therapeutic effects of Compound Cortex Phellodendri Liquid (Huangbai liniment). The main components of Compound Cortex Phellodendri Liquid were analysed via network pharmacology. The target of phellodendrine was further analysed. Caco-2 cells were cultured, and H₂O₂ was used to stimulate in vitro cell model. Expression levels of LC3, AMPK, p-AMPK, mTOR and p-mTOR were detected via Western blotting and through immunofluorescence experiments. The therapeutic effects of phellodendrine were analysed via expression spectrum chip sequencing. The sequencing of intestinal flora further elucidated the therapeutic effects of phellodendrine. Compared with the control group, Compound Cortex Phellodendri Liquid could substantially improve the healing of intestinal mucosa. Network pharmacology analysis revealed that phellodendrine is the main component of Compound Cortex Phellodendri Liquid. Moreover, this alkaloid targets the AMPK signalling pathway. Results of animal experiments showed that phellodendrine could reduce the intestinal damage of UC compared with the model group. Findings of cell experiments indicated that phellodendrine treatment could activate the p-AMPK /mTOR signalling pathway, as well as autophagy. Expression spectrum chip sequencing showed that treatment with phellodendrine could promote mucosal healing and reduce inflammatory responses. Results of intestinal flora detection demonstrated that treatment with phellodendrine could increase the abundance of flora and the content of beneficial bacteria. Phellodendrine may promote autophagy by regulating the AMPK-mTOR signalling pathway, thereby reducing intestinal injury due to UC.     

氯化两面针碱对小鼠溃疡性结肠炎的干预作用及其机制*

目的:探讨氯化两面针碱(NC)通过靶向miR-31对葡聚糖硫酸钠(DSS)诱发小鼠结肠炎的保护作用及其机制。方法:用1%DSS诱发小鼠溃疡性结肠炎(UC)。30只雄性C57BL/6小鼠随机分为正常对照组(Control)(n=7),DSS组(n=8),DSS+NC组(7.27 mg/kg)(n=8)和NC组(n=7),饮水给予DSS,灌胃给予氯化两面针碱。造模周期为3周,分别为Control组和NC组每天饮用无菌水,DSS组和DSS+NC组第一周饮用1% DSS水,第2周正常饮水,第3周1% DSS水。造模最后一周给予Control组和DSS组小鼠0.5% 羧甲基纤维素钠(CMC-Na)灌胃,DSS+NC组和NC组给予NC灌胃。造模完成后,观察小鼠结肠炎相关的疾病活动指数(DAI),HE染色进行结肠组织病理评分,qPCR检测小鼠结肠组织miR-31的表达水平,Western blot检测小鼠结肠组织炎症蛋白NF-κB和COX-2的表达情况。结果:①与DSS组相比,DSS+NC组的 DAI 显著降低(P＜0.01),结肠病理损伤明显改善;②与Control组相比,DSS组小鼠结肠组织miR-31表达显著升高(P＜0.01),DSS+NC组miR-31的表达水平显著低于DSS组(P＜0.05);③与DSS组相比,DSS+NC组中的炎症蛋白NF-κB和COX-2表达水平显著下降(P＜0.05)。结论:氯化两面针碱对DSS诱导的小鼠溃疡性结肠炎有明显的治疗作用,其抗炎机制与下调miR-31的表达有关。     

6-姜烯酚对溃疡性结肠炎小鼠结肠上皮细胞Notch信号通路的影响

目的:观察6-姜烯酚对溃疡性结肠炎小鼠结肠上皮细胞Notch信号通路的调控作用。方法:清洁级昆明小鼠40只随机分为正常组(10只)和造模组(30只),造模组采用2%葡聚糖硫酸钠(DSS)自由饮用诱导溃疡性结肠炎模型,造模15 d后分为模型组,6-姜烯酚组,阳性对照组,每组10只。正常组、模型组灌胃生理盐水,6-姜烯酚组采用6-姜烯酚100 mg/(kg·d)灌胃,阳性对照组采用柳氮磺吡啶100 mg/(kg·d)灌胃,给药20 d后处死,观察小鼠结肠病理组织学改变,免疫荧光双标法检测结肠上皮细胞Hes-1、Math-1蛋白的表达,RT-PCR法检测结肠上皮组织Notch-1、Hes-1、Math-1 mRNA的表达,Western blot法检测结肠上皮组织Notch-1、Hes-1、Math-1蛋白的表达。结果:与正常组相比,模型组小鼠结肠上皮组织Notch-1、Hes-1蛋白和mRNA相对表达量显著升高( P＜0.01), Math-1蛋白和mRNA相对表达量显著降低( P＜0.01);与模型组比较,6-姜烯酚组、柳氮磺吡啶组小鼠结肠上皮组织Notch-1、Hes-1蛋白和mRNA相对表达量显著降低( P＜0.01), Math-1蛋白和mRNA相对表达量显著升高( P＜0.01) 。结论:6-姜烯酚能够抑制Notch通路的过度活化,调节结肠上皮吸收细胞系和分泌细胞系之间分化的平衡,修复受损结肠粘膜组织。