Peroxisome proliferator-activated receptor gamma activation promotes intestinal barrier function by improving mucus and tight junctions in a mouse colitis model

Background and aimsDefects in mucus and intestinal epithelia can lead to intestinal inflammation in colitis. Reduced peroxisome proliferator-activated receptor gamma (PPAR_γ) in the mucosa may contribute to inflammation. However, the roles of PPAR_γ in the intestinal barrier remain poorly understood.MethodsChronic colitis was induced in C57BL/6 mice by administration of dextran sulfate sodium (DSS) for 27 days. Three days before DSS treatment, mice were treated with the PPAR_γ agonist rosiglitazone (Ro) orally at 20 mg kg⁻¹ day⁻¹.ResultsThe colitis based on disease activity index and colonic histopathology was significantly ameliorated in the DSS + Ro group. Additionally, mice in the DSS + Ro group had a thicker mucous layer than those in DSS + NS group, and muc2 mRNA expression was elevated significantly along with the mouse atonal homolog, SAM-pointed domain-containing Ets-like factor, and anterior gradient 2 genes. Moreover, tight junctions were up-regulated, whereas long myosin light chain kinase and phosphorylation of the myosin II light chain were lower in DSS + Ro mice. Similarly, after HT-29 and Caco-2 cells were treated by LPS or LPS + Ro, PPAR_γ activation by Ro could effectively improve the intestinal barrier, including intestinal mucus and tight junctions.ConclusionsOur results demonstrate that activated PPAR_γ could effectively promote intestinal mucus integrity by increasing the number of goblet cells, the glycosylation of mucins, and tight junctions via an MLCK-dependent mechanism.     

The Effect of Melatonin on Plasma Markers of Inflammation and on Expression of Nuclear Factor-Kappa Beta in Acetic Acid-Induced Colitis in the Rat

Background and Aims

Melatonin may be involved in gastrointestinal tract physiology and could affect inflammation-related gastrointestinal disorders. Rat models of ulcerative colitis imply melatonin is beneficial. To determine potential pathophysiological mechanisms, we assessed colonic nuclear factor-kappa beta expression and measured serum levels of pentraxin-3, lipid peroxides, and total thiols in an acetic acid model of this disease.

Materials and Methods

Thirty rats were divided into five groups: a control group, an acetic acid-induced colitis group, a group treated with melatonin before colitis induction, a group treated short-term after colitis induction, and a group treated long-term after colitis induction. After four weeks, blood samples were taken for measurement of pentraxin-3, lipid peroxide, and total thiols. Sections of the colon were taken for histopathological examination and immunohistochemical detection of nuclear factor-kappa beta expression.

Results

Melatonin administration reduced nuclear factor-kappa beta immunohistochemical expression, reduced serum levels of lipid peroxide and pentraxin-3, and maintained serum levels of total thiols. However, in long-term treatment the protective effect of melatonin was not as marked.

Conclusion

Melatonin is effective in prevention and short-term treatment of the inflammatory process in acetic-acid induced colitis whereas the benefit of long-term treatment is unclear. Benefit may be linked to protection mechanisms against inflammatory processes by inhibiting the nuclear factor-kappa beta and conserving endogenous antioxidant reserves of total thiols, thus reducing the level of colonic damage possibly caused by lipid peroxides.     

Role of melatonin in sleep deprivation‐induced intestinal barrier dysfunction in mice

Intestinal diseases caused by sleep deprivation (SD) are severe public health threats worldwide. This study focuses on the effect of melatonin on intestinal mucosal injury and microbiota dysbiosis in sleep‐deprived mice. Mice subjected to SD had significantly elevated norepinephrine levels and decreased melatonin content in plasma. Consistent with the decrease in melatonin levels, we observed a decrease of antioxidant ability, down‐regulation of anti‐inflammatory cytokines and up‐regulation of pro‐inflammatory cytokines in sleep‐deprived mice, which resulted in colonic mucosal injury, including a reduced number of goblet cells, proliferating cell nuclear antigen‐positive cells, expression of MUC2 and tight junction proteins and elevated expression of ATG5, Beclin1, p‐P65 and p‐IκB. High‐throughput pyrosequencing of 16S rRNA demonstrated that the diversity and richness of the colonic microbiota were decreased in sleep‐deprived mice, especially in probiotics, including Akkermansia, Bacteroides and Faecalibacterium. However, the pathogen Aeromonas was markedly increased. By contrast, supplementation with 20 and 40 mg/kg melatonin reversed these SD‐induced changes and improved the mucosal injury and dysbiosis of the microbiota in the colon. Our results suggest that the effect of SD on intestinal barrier dysfunction might be an outcome of melatonin suppression rather than a loss of sleep per se. SD‐induced intestinal barrier dysfunction involved the suppression of melatonin production and activation of the NF‐κB pathway by oxidative stress.     

Melatonin reduces the severity of dextran-induced colitis in mice

Abstract: Melatonin administration reduces the severity of dextran sodium sulphate (DSS)-induced colitis in mice. After 7 weeks of daily intraperitoneal melatonin administration (150 μg/kg), rectal bleeding and occult blood was eliminated in all mice in which colitis was induced by DSS. In addition the frequency and severity of focal lesions in the mucosa was dramatically reduced. Furthermore, weight loss and higher food consumption observed in DSS-treated mice was reversed in DSS-treated mice injected with melatonin. All treated groups exhibited significant alterations in goblet cell distribution as a result of DSS or melatonin administration. Surprisingly, serum melatonin levels were more than 10 times higher in mice that received DSS as compared to controls. The significant improvement in the conditions of melatonin-treated mice might be due to its effect on the smooth muscles of the colon, the blood supply in the mucosa, its capability as an antioxidant and scavenger of free radicals, or its effect on the immune system of the gut. The higher plasma levels of melatonin in DSS-treated mice might be due to a stress-induced increase in the production of gastrointestinal (GIT) melatonin.     

Dipeptidyl peptidase-4 inhibitor anagliptin facilitates restoration of dextran sulfate sodium-induced colitis

Abstract

Objective. Inflammatory bowel disease (IBD) is a chronic debilitating disease associated with severe damage to the intestinal mucosa. Glucagon-like peptide-2 (GLP-2) is a potent and specific gastrointestinal growth factor. GLP-2 released from enteroendocrine cells is inactivated by dipeptidyl peptidase-4 (DPP-4). The aim of this study was to examine whether the DPP-4 inhibitor anagliptin improves experimental murine colitis. Material and methods. Male C57BL/6 mice aged 8 weeks were exposed to 1.5% dextran sulfate sodium (DSS) in drinking water for 7 days to induce experimental colitis. Anagliptin (0.1% in diet) was administrated from 2 days before the beginning of DSS to 7 days after the end of DSS. Changes in body weight and disease activity index were evaluated daily. Histological colitis severity, cellular proliferation and gene expression were determined in colonic tissues. Results. Treatment with anagliptin clearly improved body weight loss and disease activity index in the recovery phase. Histological score in the DSS + anagliptin group at day 14 was significantly lower than that in the DSS alone group. Treatment with anagliptin increased the Ki67-positive rate at days 10 and 14, and tended to increase insulin-like growth factor-1 mRNA expression in the DSS + anagliptin group. Conclusion. In this model of experimental colitis, the DPP-4 inhibitor anagliptin facilitated the restoration of mucosal damage, thereby resulting in the acceleration of healing. These findings suggest a new and novel therapeutic approach for the treatment of IBD.     

Effect of adiponectin on murine colitis induced by dextran sulfate sodium

BACKGROUND & AIMS: Adiponectin, an adipose tissue-derived hormone, exhibits anti-inflammatory properties and has various biological functions, such as increasing insulin sensitivity, reducing hypertension, and suppressing atherosclerosis, liver fibrosis, and tumor growth. The aim of the present study was to determine the effect of adiponectin on intestinal inflammation. METHODS: We investigated the effect of adiponectin on dextran sulfate sodium (DSS)-induced colitis by using adiponectin-knockout (APN-KO) mice and an adenovirus-mediated adiponectin expression system. We also examined the contribution of adiponectin deficiency to trinitrobenzene sulfonic acid (TNBS)-induced colitis. In vitro, we examined the effect of adiponectin on intestinal epithelial cells. RESULTS: After administration of 0.5% DSS for 15 days, APN-KO mice developed much more severe colitis compared with wild-type mice. The messenger RNA expression levels of chemokines were significantly higher in the colonic tissues of DSS-treated APN-KO mice compared with wild-type mice, accompanied by increased cellular infiltration, including macrophages. Adenovirus-mediated supplementation of adiponectin significantly attenuated the severity of colitis, but there were no differences in the severity of TNBS-induced colitis between the 2 groups. Adiponectin receptors were expressed in intestinal epithelial cells, and adiponectin inhibited lipopolysaccharide-induced interleukin-8 production in intestinal epithelial cells. CONCLUSIONS: Adiponectin is protective against DSS-induced murine colitis, probably due to the inhibition of chemokine production in intestinal epithelial cells and the following inflammatory responses, including infiltration of macrophages and release of proinflammatory cytokines.     

Potential Role of Heme Oxygenase-1 in the Resolution of Experimentally Induced Colitis through Regulation of Macrophage Polarization

Background/AimsHeme oxygenase-1 (HO-1) plays a central role in cellular defense against inflammatory insults, and its induction in macrophages potentiates their efferocytic activity. In this study, we explored the potential role of macrophage HO-1 in the resolution of experimentally induced colitis.MethodsTo induce colitis, male C57BL/6 mice were treated with 2% dextran sulfate sodium (DSS) in the drinking water for 7 days. To investigate efferocytosis, apoptotic colon epithelial CCD 841 CoN cells were coincubated with bone marrow-derived macrophages (BMDMs).ResultsAdministration of the HO-1 inhibitor zinc protoporphyrin IX (ZnPP) blunted the resolution of DSS-induced intestinal inflammation and expression of the proresolving M2 macrophage marker CD206. BMDMs treated with apoptotic colonic epithelial cells showed significantly elevated expression of HO-1 and its regulator Nrf2. Under the same experimental conditions, the proportion of CD206-expressing macrophages was also enhanced. ZnPP treatment abrogated the upregulation of CD206 expression in BMDMs engulfing apoptotic colonic epithelial cells. This result was verified with BMDMs isolated from HO-1-knockout mice. BMDMs, when stimulated with lipopolysaccharide, exhibited increased expression of CD86, a marker of M1 macrophages. Coculture of lipopolysaccharide-stimulated BMDMs with apoptotic colonic epithelial cell debris dampened the expression of CD86 as well as the pro-inflammatory cytokines in an HO-1-dependent manner. Genetic ablation as well as pharmacologic inhibition of HO-1 significantly reduced the proportion of efferocytic BMDMs expressing the scavenger receptor CD36.ConclusionsHO-1 plays a key role in the resolution of experimentally induced colitis by modulating the polarization of macrophages.     

Effects of melatonin on the expression of iNOS and COX－2 in rat models of colitis

AIM: To investigate the effects of melatonin (MT) on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in rat models of colitis. METHODS: Healthy adult Sprague-Dawlay (SD) rats of both sexes, weighing 280+/-30 g, were employed in the present study. The rat models of colitis were induced by either acetic acid or 2,4,6-trinitrobenzene sulfonic acid (TNBS) enemas. The experimental animals were randomly divided into melatonin treatment and model control group that were intracolicly treated daily with melatonin at doses of 2.5, 5.0, 10.0 mg/kg(-1) and equal amount of saline respectively from 24 h following induction of colitis in rats inflicted with acetic acid enema and the seventh day in rats with TNBS to the end of study. A normal control group of rats treated with neither acetic acid nor TNBS but saline enema was also included in the study. On the 28(th) day of the experiment, the rat colon mucosal damage index (CDMI) was calculated, and the colonic prostaglandin E(2) (PGE(2)), nitric oxide (NO), as well as the iNOS and COX-2 expression were also determined biochemically or immunohistochemically. RESULTS: CDMI increased to 2.87+/-0.64 and 3.12+/-1.12 respectively in rats treated with acetic acid and TNBS enema, which was in accordance with the significantly elevated colonic NO and PGE(2) contents, as well as the up-regulated colonic iNOS and COX-2 expression in both of the two rat models of colitis. With treatment by melatonin at the doses of 5.0 and 10.0 mg/kg(-1), CDMI in both models of rat colitis was significantly decreased (P<0.05-0.01), which accorded synchronously and unanimously with the reduced colonic NO and PGE(2) content, as well as the down-regulated expression of colonic iNOS and COX-2. CONCLUSION: Melatonin has a protective effect on colonic injury induced by both acetic acid and TNBS enemas, which is probably via a mechanism of local inhibition of iNOS and COX-2 expression in colonic mucosa.     

Melatonin ameliorates acute necrotizing pancreatitis by the regulation of cytosolic Ca2+ homeostasis

ObjectivesThis study aims to investigate the relationship between the protective effects of melatonin in pancreas and the expression of sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA) and Na⁺/Ca²⁺ exchanger (NCX) in rats with acute necrotizing pancreatitis (ANP), to verify whether melatonin ameliorates ANP by alleviating calcium overload.MethodsNinety-six male Sprague-Dawley rats were randomly divided into four groups (sham operation group, ANP group, melatonin treatment group, melatonin contrast group). ANP was induced by the retrograde injection of 4% taurocholate (1 ml/kg body weight) into the biliopancreatic duct. Melatonin (50 mg/kg body weight) was administered 30 min before the induction of ANP in the melatonin treatment group. Rats in each group were euthanized at 1, 4, and 8 h after ANP induction. Pancreatic tissues were removed to measure SERCA and NCX levels and cytosolic calcium ion (Ca²⁺) concentration ([Ca²⁺]_i).ResultsAt each time point, SERCA and NCX levels in the melatonin treatment group were significantly higher than that in the ANP group, and lower than that in the sham group and the melatonin contrast group. These levels did not differ between the 4- and 8-h time points in the ANP group. [Ca²⁺]_i in pancreatic acinar cells was higher in the melatonin treatment group than in the sham group and the melatonin contrast group, but lower than in the ANP group, at each time point.ConclusionMelatonin can reduce pancreatic damage via the up-regulation of SERCA and NCX expression, which can alleviate calcium overload in pancreatic acinar cells.     

Premorbid Steatohepatitis Increases the Seriousness of Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice

Background and AimsThe concurrence of nonalcoholic steatohepatitis (NASH) and ulcerative colitis (UC) is increasingly seen in clinical practice, but the underlying mechanisms remain unclear. This study aimed to develop a mouse model of the phenomenon by combining high-fat high-cholesterol diet (HFHCD)-induced NASH and dextran sulfate sodium (DSS)-induced UC, that would support mechanistic studies.MethodsMale C57BL/6 mice were randomly assigned to two groups receiving either a chow diet or HFHCD for 12 weeks of NASH modeling. The mice were the divided into four subgroups for UC modeling: (1) A control group given a chow diet with normal drinking water; (2) A colitis group given chow diet with 2% DSS in drinking water; (3) A steatohepatitis group given HFHCD with normal drinking water; and (4) A steatohepatitis + colitis group given HFHCD with 2% DSS in drinking water.ResultsNASH plus UC had high mortality (58.3%). Neither NASH nor UC alone were fatal. Although DSS-induced colitis did not exacerbate histological liver injury in HFHCD-fed mice, premorbid NASH significantly increased UC-related gut injury compared with UC alone. It was characterized by a significantly shorter colon, more colonic congestion, and a higher histopathological score (p<0.05). Inflammatory (tumor necrosis factor-alpha, interleukin 1 beta, C-C motif chemokine ligand 2, and nuclear factor kappa B) and apoptotic (Bcl2, Bad, Bim, and Bax) signaling pathways were significantly altered in distal colon tissues collected from mice with steatohepatitis + colitis compared with the other experimental groups.ConclusionsPremorbid steatohepatitis significantly aggravated DSS-induced colitis and brought about a lethal phenotype. Potential links between NASH and UC pathogeneses can be investigated using this model.     

Protective action of NADPH oxidase inhibitors and role of NADPH oxidase in pathogenesis of colon inflammation in mice

AIM: To investigate the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in colon epithelial cells in the pathogenesis of acute and chronic colon inflammation in a mouse model of dextran sulphate sodium (DSS)-induced colitis.METHODS: Balb/c mice were divided into three groups: 8 mice with acute DSS-induced colitis (3.5% DSS solution; 7 d), 8 mice with chronic DSS-induced colitis (3.5% DSS solution for 5 d + water for 6 d; 4 cycles; total: 44 d) and 12 mice without DSS supplementation as a control group. Primary colonic epithelial cells were isolated using chelation method. The cells were cultivated in the presence of mediators (lipopolysaccharide (LPS), apocynin or diphenyleneiodonium). Viability of cells was assessed by fluorescent microscopy. Production of reactive oxygen species (ROS) by the cells was measured fluorometrically using Amplex Red. Production of tumour necrosis factor-alpha (TNF-α) by the colonic epithelial cells was analysed by ELISA. Nox1 gene expression was assessed by real-time PCR.RESULTS: Our study showed that TNF-α level was increased in unstimulated primary colonic cells both in the acute and chronic colitis groups, whereas decreased viability, increased ROS production, and expression of Nox1 was characteristic only for chronic DSS colitis mice when compared to the controls. The stimulation by LPS increased ROS generation via NADPH oxidase and decreased cell viability in mice with acute colitis. Treatment with NADPH oxidase inhibitors increased cell viability and decreased the levels of ROS and TNF-α in the LPS-treated cells isolated from mice of both acute and chronic colitis groups.CONCLUSION: Our study revealed the importance of NADPH oxidase in the pathogenesis of both acute and chronic inflammation of the colon.     

Antioxidative potential of a combined therapy of anti TNFα and Zn acetate in experimental colitis

AIM:To evaluate whether combination therapy with antitumour necrosis factor α (TNFα) antibody and Zn acetate is beneficial in dextran sodium sulphate (DSS) colitis.METHODS:Colitis was induced in CD1-Swiss mice with 5% DSS for 7 d.The experimental mice were then randomised into the following subgroups:standard diet + DSS treated (induced colitis group);standard diet + DSS + subcutaneous 25 μg anti-TNFα treated group;Zn acetate treated group + DSS + subcutaneous 25 μg anti-TNFα;standard diet + DSS + subcutane...     

Geranylgeranylacetone protects mice from dextran sulfate sodium-induced colitis

Objective. Geranylgeranylacetone (GGA) has recently been reported to induce heat shock protein (HSP) 70, which has a protective function against inflammation. We investigated the therapeutic effects of oral administration of GGA on dextran sulfate sodium (DSS)-induced colitis in mice.Material and methods. BALB/c mice were given 3% DSS solution orally for 7?days to induce colitis. The disease activity of colitis was assessed clinically every day, and histology in the colon was evaluated at 7?days post-DSS. The levels of myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in the colon tissues were also examined. In addition, expression of HSPs 25, 40, 70 and 90 in the colon tissue was determined by Western blot analysis. Mice were orally administered GGA (50–500?mg/kg) when treatment of DSS started.Results. It was found that GGA significantly reduced the clinical severity of colitis and suppressed the levels of MPO activity, TNF-α and IFN-γ induced by DSS in the colon. On the other hand, GGA enhanced the expression of HSP70 in the colon of mice given DSS. HSP70-positive cells were identified in the epithelial cells of the colon from mice treated with GGA and DSS.Conclusions. Taken together, these results suggest that GGA is a new anti-inflammatory drug that could be useful in the treatment of colitis such as inflammatory bowel disease.     

乳酸杆菌联合丁酸梭菌治疗小鼠溃疡性结肠炎的研究

目的观察联用乳酸杆菌和丁酸梭菌对小鼠急性溃疡性结肠炎的疗效并探讨其治疗机制。方法70只小鼠随机分为7组,正常对照组：正常饮食,无特殊处理;模型组：饮用DSS造模;阴性对照组：仅用无菌0.9%氯化钠溶液灌胃;阳性对照组：用巴柳氮（40mg/ml）灌胃;乳酸杆菌组：DSS造模＋2×1010/ml乳酸杆菌菌液灌胃;丁酸梭菌组：DSS造模＋2×108/ml丁酸梭菌菌液灌胃;合用组：DSS造模＋（2×1010/ml乳酸杆菌菌液＋2×108/ml丁酸梭菌菌液灌胃。建立DSS诱导的小鼠急性溃疡性结肠炎模型,观察给予乳酸杆菌和丁酸梭菌治疗后,小鼠结肠黏膜的病理改变和EMAP-Ⅱ表达的变化。结果乳酸杆菌和丁酸梭菌可明显减轻小鼠结肠黏膜的损伤;可明显抑制EMAP-Ⅱ的表达,尤以两菌合用组抑制作用最强。结论乳酸杆菌和丁酸梭菌对DSS诱导的溃疡性结肠炎有治疗作用,对EMAP-Ⅱ表达的抑制作用可能是其发挥治疗作用的部分分子机制。     

肥大细胞在葡聚糖硫酸钠诱导大鼠结肠炎中的致炎作用研究

目的 研究肠黏膜且巴大细胞(IMMC)在葡聚糖硫酸钠(DSS)诱导结肠炎时的致炎作用。方法 SD大鼠18只,随机分为DSS诱导大鼠结肠炎模型组(10只)和正常对照组(8只)。1周内模型组饮用3％DSS溶液,对照组饮水,观察大鼠的腹泻、便血症状及结肠组织学改变,用荧光法测定结肠组织组胺浓度,ELISA法测定结肠组织肿瘤坏死因子-a(TNF -a)和前列腺素E2(PGE2)水平.组化法对IMMC染色并记数。结果 DSS诱导的模型组第7天开始出现腹泻、便血,结肠黏膜组织学检查有明显损伤,和对照组比较:结肠组织组胺水平降低,TNF-a和PGE2显著升高,IMMC计数增多(P均<0.05),脱颗粒现象明显。结论结肠IMMC具有明显的致炎作用,其机制是IMMC活化及促组胺释放,引发肥大细胞--细胞因子级联反应,促进TNF-a和PGE2的生成,导致腹泻,便血等症状。     

Melatonin attenuates lipopolysaccharide-induced acute lung inflammation in sleep-deprived mice

Abstract:  Sleep disorders are great problems in modern society. Even minimal changes of sleep can affect health. Especially, patients with pulmonary diseases complain of sleep problems such as sleep disturbance and insomnia. Recent studies have shown an association between sleep deprivation (SD) and inflammation, however, the underlying mechanisms remain unclear. In the present study, we investigated whether melatonin protects against acute lung inflammation in SD. Male ICR mice were deprived sleep using modified multiplatform water bath for 3 days. Acute lung inflammation was induced by lipopolysaccharide (LPS; 5 mg/kg). Melatonin (5 mg/kg) and LPS was administered in SD mice at day 2. Mice were divided into five groups as control, SD, LPS, LPS + SD, and LPS + SD + melatonin (each group, n = 11). Mice were killed on day 3 after treatment of melatonin and LPS for 24 hr. Lung tissues were collected for histological examination and protein analysis. The malondialdehyde (MDA) level was determined for the effect of oxidative stress. Melatonin restored weight loss in LPS + SD. Histological findings revealed alveolar damages with inflammatory cell infiltration in LPS + SD. Melatonin remarkably attenuated the alveolar damages. In western blot analysis, LPS reduced the levels of Bcl-XL and procaspase-3 in SD mice. After treatment with melatonin, the levels of Bcl-XL and procaspase-3 increased when compared with LPS + SD. LPS treatment showed an increase of TUNEL-positive cells, whereas melatonin prevented the increase of cell death in LPS + SD animals. In lipid peroxidation assay, melatonin significantly reduced the elevated MDA level in LPS + SD. Our results suggest that melatonin attenuates acute lung inflammation during SD via anti-apoptotic and anti-oxidative actions.     

低分子量肝素对实验性小鼠结肠炎的治疗作用及其机制初探

背景:肝素具有抗凝和抗炎的双重作用,但其抗炎机制仍不明确。目的:通过观察低分子量肝素对葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎结肠黏膜Syndecan-1(Sdc-1)mRNA和蛋白表达以及白细胞介素(IL)-1β mRNA表达的影响,在一定程度上阐明低分子量肝素抗炎的分子机制。方法:54只C57BL/6小鼠分为正常对照组、模型组和治疗组。小鼠饮用3%DSS溶液5d后改饮用蒸馏水2周,建立急性结肠炎慢性化模型,治疗组皮下注射低分子量肝素。实验第5、12、19d分别处死6只小鼠。行组织学评分,以RT-PCR法检测结肠黏膜Sdc-1、IL-1β mRNA表达,以免疫组化法检测结肠黏膜Sdc-1蛋白表达。结果:与正常对照组相比,模型组各时间点组织学评分、IL-1β mRNA表达显著升高(P0.05),Sdc-1 mRNA和蛋白表达显著降低(P0.05)。经低分子量肝素治疗后,上述各指标明显改善。结论:在DSS诱导的小鼠急性结肠炎慢性化过程中,低分子量肝素可能通过下调炎症介质IL-1β表达而起抗炎作用,并可能通过替代从细胞表面丢失的Sdc-1而加速修复过程,促进结肠炎的愈合。