Population changes in immunoglobulin-containing mononuclear cells in dextran sulfate sodium-induced coltitis

To investigate the relation of immunoglobulin-containing cells in the colonic mucosa to mucosal inflammation, we immunohistochemically examined the localization of immunoglobulin-containing mononuclear cells in the lamina propria in dextran sulfate sodium induced colitis in mice. Mice were treated repeatedly with 3% dextran sulfate sodium (MW 54 000) solution or distilled water for a total of 170 days (chronic model), or for 85 days (subacute model) or for 10 days (acute model). IgG, IgA, and IgM-containing mononuclear cells were studied by enzyme immunostaining. The number of IgA- and IgG-containing cells gradually and significantly increased in the acute, subacute, and chronic models, in that order (P<0.01 or 0.05). However, the numbers of IgM-containing cells in the three models were similar to that in the controls. These findings resembled those of human ulcerative colitis. In this dextran sulfate sodium-induced colitis, IgA-containing mononuclear cells may play an essential role in the mucosal immune system is the acute, subacute, and chronic phases. The finding that IgG-containing mononuclear cells increased substantially in the chronic phase suggests that IgG plays an important role in the mucosal inflammatory reaction during the chronic phase.     

Nonpathogenic Escherichia coli strain Nissle1917 prevents murine acute and chronic colitis

BACKGROUND: Nonpathogenic Escherichia coli strain Nissle1917 has been used as a probiotics in human inflammatory bowel disease; however, there are few reports examining its therapeutic effect on animal colitis models, and its therapeutic mechanisms remain unknown. The aim of this study was to elucidate the therapeutic effect and mechanism of Nissle1917 using murine acute and chronic colitis models. METHODS: Two models were used. (1) Acute model: colitis was induced by administration of 1.3% dextran sodium sulfate for 7 days. Nissle1917 or phosphate-buffered saline were orally administered for 10 days. Mice were killed at day 10, and the colonic lesions were assessed macro- and microscopically. (2) Chronic model: IL-10 mice were treated with Nissle1917 or phosphate-buffered saline for 8 weeks. After 8 weeks of treatment, mice were killed to assess the colonic lesions macro- and microscopically. In the acute dextran sodium sulfate colitis model, viable, heat-killed, or genomic DNA of Nissle1917 was orally administered for 10 days, and the therapeutic effect was assessed. RESULTS: In the acute model, Nissle1917 ameliorated body weight loss, disease activity index, and macro- and microscopic damage. In the chronic model, it also suppressed the mucosal inflammatory findings and histologic damages. Moreover, heat-killed Nissle1917 or its genomic DNA alone also ameliorated the acute DSS colitis and viable bacteria macro- and microscopically. CONCLUSIONS: Nonpathogenic E. coli strain Nissle1917 prevents both acute and chronic colitis, and its anti-inflammatory effect is exhibited not only by viable bacteria but also by heat-killed bacteria or its DNA.     

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。     

The role of the resident intestinal flora in acute and chronic dextran sulfate sodium-induced colitis in mice

OBJECTIVE: There is increasing evidence that the intestinal microflora plays an important role in the pathogenesis of inflammatory bowel disease. In the present study, we examined the role of the resident intestinal flora in our model of dextran sulfate sodium (DSS)-induced acute and chronic colitis in mice. METHODS: Acute colitis was induced in BALB/c mice with 5% DSS in their drinking water for 7 days. Chronic colitis was established after four cycles of feeding 5% DSS for 7 days and water for 10 days. For eliminating intestinal bacteria, mice were injected intraperitoneally with metronidazole and ciprofloxacin. We analysed four parameters: (1) body weight, (2) length of the colon, (3) histological score, and (4) myeloperoxidase activity. RESULTS: In acute DSS colitis treatment with antibiotics led to an improvement of the histological parameters (epithelial damage, P< 0.05; inflammatory infiltrate, P< 0.05) and colon length (P < 0.0028). A significant reduction in granulocyte infiltration was indicated by a 52.6% reduced myeloperoxidase activity in colonic biopsies. By contrast, in chronic colitis, treatment of mice with antibiotics failed to show significant effects. CONCLUSION: In acute DSS-induced colitis bacteria and/or bacterial products play a major role in initiation of inflammation but not in chronic DSS colitis.     

pVAX1-A20 alleviates colitis in mice by promoting regulatory T cells

AimTo investigate whether the intrarectal administration of the ubiquitin E3 ligase A20 (A20) attenuates intestinal inflammation and influences regulatory T cells in experimental colitis.MethodsA dextran sulfate sodium induced chronic colitis mouse model was established. The symptoms and manifestations of colitis and the severity of colonic mucosal inflammation were evaluated. The protective role of A20 expression in the intestine was analyzed after the administration of a pVAX1-A20 recombinant eukaryotic vector, which was encapsulated into poly(L-lactide-co-glycolide) as a nanoparticle.ResultspVAX1-A20 administration markedly ameliorated colonic tissue damage and reduced intestinal inflammation via the suppression of the mucosal mitogen-activated protein kinase and nuclear factor (NF)-κB signaling cascade. Furthermore, pVAX1-A20 promoted the splenic regulatory T cell population and forkhead box P3 expression in colonic tissue.ConclusionA20 plays a key role in the regulation of intestinal inflammation and that the overexpression of A20 in the intestine protects mice from dextran sulfate sodium induced chronic colitis.     

Antibody to eosinophil cationic protein suppresses dextran sulfate sodium-induced colitis in rats

AIM: To produce an antibody against rat eosinophil cationic protein (ECP) and to examine the effects of the antibody in rats with dextran sulfate sodium (DSS)-induced colitis. METHODS: An antibody was raised against rat ECP. Rats were treated with 3% DSS in drinking water for 7 d and received the antibody or normal serum. The colons were examined histologically and correlated with clinical symptoms. Immunohistochemistry and Western blot analysis were estimated as a grade of inflammation. RESULTS: The ECP antibody stained the activated eosinophils around the injured crypts in the colonic mucosa. Antibody treatment reduced the severity of colonic ulceration and acute clinical symptoms (diarrhea and/or bloodstained stool). Body weight gain was significantly greater and the colon length was significantly longer in anti-ECP-treated rats than in normal serum-treated rats. Expression of ECP in activated eosinophils was associated with the presence of erosions and inflammation. The number of Ki-67-positive cells in the regenerated surface epithelium increased in anti-ECP-treated rats compared with normal serum-treated rats. Western blot analysis revealed reduced expression of macrophage migration inhibitory factor (MIF) in anti-ECP-treated rats. CONCLUSION: Our results indicate that treatment with ECP antibody, improved DSS-induced colitis in rats, possibly by increasing the regenerative activity of the colonic epithelium and downregulation of the immune response, and suggest that anti-ECP may promote intestinal wound healing in patients with ulcerative colitis (UC).     

Dextran Sulfate Sodium-Induced Colitis Is Associated with Enhanced Low Molecular Mass Polypeptide 2 (LMP2) Expression and Is Attenuated in LMP2 Knockout Mice

Low molecular mass polypeptide 2 (LMP2) is an inducible proteasome subunit. Our goals were to examine LMP2 expression in mice with dextran sulfate sodium (DSS)-induced colitis and to evaluate colitis in LMP2 knockout (LMP2-/-) mice. Mice were given 2.5% DSS in the drinking water. On day 0, 2, 4, or 6 after DSS treatment, LMP2 expression was determined in the distal colon by western blot and immunohistochemistry. Parameters of colitis were measured in LMP2-/- mice or wild-type mice. LMP2 expression was enhanced in the colon of DSS-treated mice at all time points. Symptoms of DSS-induced colitis were always lower in LMP2-/- mice. Normalized histology scores and colonic IL-1ss levels increased over the 6-day study period in wild-type mice. These parameters were significantly reduced in LMP2-/- mice that consumed DSS for 6 days. Enhanced LMP2 expression contributes to the pathogenesis of DSS-induced colitis in mice.     

葡聚糖硫酸钠自由饮用与定量灌胃诱导小鼠急性结肠炎模型的比较研究

背景：自由饮用葡聚糖硫酸钠（DSS）诱导的鼠类急性结肠炎模型均一性欠佳,动物死亡率较高。目的：评估2%DSS自由饮用或定量灌胃诱导的小鼠急性结肠炎模型模拟人类溃疡性结肠炎（UC）的效果和均一性。方法：予ICR小鼠2%DSS自由饮用或定量灌胃建立急性结肠炎模型,检测并比较正常对照组和两组模型小鼠的症状出现时间和频率、疾病活动指数（DAI）、DSS消耗量、死亡率、结肠长度、结肠损伤大体评分（MACD）、结肠组织病理学表现以及外周血白细胞计数和分类。结果：两组模型小鼠均出现类似人类UC的症状和组织病理学改变,结肠显著短缩,DAI、MACD以及外周血白细胞计数和中性粒细胞百分比显著高于正常对照组。与DSS自由饮用组相比,DSS定量灌胃组小鼠症状出现时间更为一致,症状出现率显著增高,动物死亡率和DSS消耗量显著减低。结论：2%DSS定量灌胃诱导的小鼠急性结肠炎模型能较稳定地模拟人类UC,均一性高,动物死亡率低。     

Effect of Scutellariae Radix extract on experimental dextran-sulfate sodium-induced colitis in rats

AIM： To investigate the effect of Scutellariae Radix extract （SRE） on ulcerative colitis （UC） in rats induced by dextran-sulfate sodium （DSS）. METHODS： Colitis was induced in male Sprague-Dawley （SD） rats （170-180 g） by 4% dextran sulfate sodium （DSS, wt/v, MW 54000） in drinking water for 8 d. The treated rats received 4% DSS and SRE orally （100 mg/kg per day）. Control rats received either tap water or SRE only. Macroscopic assessment which included body weight changes, fecal occult blood and stool consistency were determined daily. At the appointed time, the rats were sacrificed and the entire colons were removed. The colon length and the myeloperoxidase （MPO） activity were measured. The severity of colitis was graded by morphological and histological assessments. The ion transport activity of the colonic mucosa was assessed by electrophysiological technique. RESULTS： Rats treated with oral administration of 4% DSS regularly developed clinical and macroscopic signs of colitis. Treatment with SRE relieved the symptoms, including the reduction in body weight, shortening 2nd ulceration of the colon. Administration of SRE also significantly reduced the histological damage induced by DSS. Moreover, the Isc responses of the colonic mucosa to forskolin, were suppressed after the induction of colitis. The stimulated ion transport activity of DSS-rats treated with SRE displayed significant improvement in the secretory responsiveness. CONCLUSION： SRE was effective in treating acute DSS- induced ulcerative colitis, as gauged by reduced clinical disease, improved macroscopic and histological damage scores, and enhanced recovery of normal colonic secretory function.     

Clinical and histopathological features of dextran sulfate sodium induced acute and chronic colitis associated with dysplasia in rats

We examined the clinical and histopathological features of the dextran sulfate sodium (DSS) induced acute and chronic colitis in rats as a model for studying basic biology of the inflamed colonic mucosa. Acute colitis was induced in male Wistar rats by 4 days (AI) or 7 days (AII) of oral 5% (wt/vol) DSS (mol. wt. 54,000) in their drinking water. Chronic colitis was induced in 8 experimental groups: CI=7 days DSS followed by 10 days water (=one cycle); CII=two cycles; CIII to CVIII (three to eight cycles) received only 4 days 5% DSS followed by 10 days drinking water. The entire colons were examined histologically; dysplasia was graded as: indefinite/probably negative for dysplasia, indefinite/probably positive for dysplasia, low-grade dysplasia, or high-grade dysplasia. The earliest clinical findings in the acute colitis group over 4 days occurred on day 2 (hemoccult positive stools, loose stools or diarrhea and weight loss). The maximal disease activity was noted on day 7 accompanied by a 53% mortality rate. The histological inflammation scores were significantly higher on day 7 than on day 4. All rats had extensive ulcerations predominantly in the rectum and cecum. The number of rats having ulcerations was markedly lower in the chronic colitis groups. The majority (75%) of the crypt lesions suspicious for dysplasia were classified as mucosa indefinite/probably negative for dysplasia. We classified 18 crypt lesions as low-grade dysplasia and one lesion as high-grade dysplasia (after eight cycles). No invasive carcinoma was observed. Most low-grade dysplasias (83%) occurred after five cycles of DSS/water, located mostly in the rectum (44%) and colon transversum (33%). Our findings suggest that the DSS colitis model in rats may be an interesting model for studying the sequence chronic inflammation-dysplasia in human ulcerative colitis. Further long-term studies with the present DSS colitis model in rats might also prove it as a reliable model to study the sequence high-grade dysplasia and colitis associated-cancer.     

Contribution of polymeric immunoglobulin receptor to regulation of intestinal inflammation in dextran sulfate sodium-induced colitis

BACKGROUND: Inflammatory bowel disease (IBD) affects approximately 4 million people worldwide and can be caused by dysregulated mucosal immune responses to the intestinal commensal microflora. Immunoglobulin A (IgA) is considered to be the principal antibody in intestinal secretions and functions to prevent commensals and pathogenic organisms from gaining access to epithelial cell surfaces. Immunoglobulin A deficiency in humans has been associated with celiac disease and ulcerative colitis. However, the precise role of IgA in the pathogenesis of these disorders is yet to be fully understood. METHODS: Mice with a targeted disruption in IgA production (IgA(-/-) mice) and polymeric immunoglobulin receptor (pIgR(-/-) mice) were analyzed for the contribution of secretory immunity in the pathogenesis of dextran sulfate sodium (2.5%)-induced colitis. RESULTS: It was found that dextran sulfate sodium-treated pIgR(-/-) mice displayed greater loss of bodyweight and had severe clinical illness compared to similarly treated IgA(-/-) mice and wild-type animals. Additionally, colonic tissues from the pIgR(-/-) mice exhibited progressively and significantly greater degrees of mucosal edema, ulceration, crypt abscesses and macrophage infiltration when compared to similarly treated IgA(-/-) mice and wild-type animals. CONCLUSIONS: The results indicate that secretory immunoglobulins contribute to protection of the colonic mucosa against dextran sulfate sodium-induced epithelial injury, although the isotype of the secretory immunoglobulin (IgA or IgM) may not be a decisive factor in such protection. Collectively, the pIgR and/or the secretory component are important for the maintenance of epithelial integrity and mucosal homeostasis in the colonic epithelium.     

慢性应激对小鼠溃疡性结肠炎的影响

目的观察慢性束缚应激对葡聚糖酸钠(DSS)诱导的小鼠溃疡性结肠炎(UC)的影响。方法64只BALB/C小鼠分为6组,单纯应激组、正常对照组各16只,应激 2DSS组、应激 4DSS组、2DSS组、4DSS组各8只。采用自制的束缚笼对应激组小鼠建立慢性心理应激动物模型。采用小鼠自由饮用DSS溶液的方法建立UC模型。每日观察各组疾病活动指数(DAI)。并在实验结束后测量结肠组织损伤评分(HS)、髓过氧化物酶(MPO)活性。HS评分通过在光镜下观察结肠组织学改变得出。并用分光光度法测定结肠组织中MPO的活性。结果单纯应激组小鼠体重增长较正常对照组缓慢(P<0.05)。4DSS组小鼠DAI评分、HS评分及结肠组织MPO活性均较正常对照组增高(P<0.05)。应激 4DSS组上述指标较正常对照组变化更显著,与4DSS组比较亦增高(P<0.05)。2DSS组上述指标与正常对照组相比无明显区别(P>0.05)。应激 2DSS组上述指标较正常对照组增高(P<0.05)。结论慢性束缚应激可以使小鼠发生UC的易感性增加并加重DSS结肠炎的病理损伤。     

Effect of Arctium lappa L. in the dextran sulfate sodium colitis mouse model

AIM:To analyze the possible protective role of Arctium lappa L.(AL)in a murine model of ulcerative colitis(UC).METHODS:BALB/c mice were administered 100 mg/kg AL powder orally each day.After 7 d,colitis was induced by administration of dextran sulfate sodium(DSS)(5% W/V)in drinking water for a further 8 consecutive days.Diarrhea and bloody stools as well as colonic histology were observed.The level of interleukin-6(IL-6)and tu-mor necrosis factor-α(TNF-α)in colonic sections were detected by immunohistochemi...     

Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice

BACKGROUND & AIMS: Effective therapeutics for treating acute colitis, caused by disruption of the intestinal epithelial barrier, are scarce. Trefoil factors (TFF) are cytoprotective and promote epithelial wound healing and reconstitution of the gastrointestinal tract, which makes them good candidate therapeutics for acute colitis. However, orally administered TFF stick to the mucus of the small intestine and are absorbed at the cecum. METHODS: We have engineered the food-grade bacterium Lactococcus lactis to secrete bioactive murine TFF. The protective and therapeutic potentials of these TFF-secreting L. lactis were evaluated in parallel with purified TFF in the dextran sodium sulfate (DSS)-induced murine model for acute colitis and in established chronic colitis in interleukin (IL)-10(-/-) mice. Disease was evaluated by blinded macroscopic and microscopic inflammatory scores and by myeloperoxidase activity. RESULTS: Intragastric administration of TFF-secreting L. lactis led to active delivery of TFF at the mucosa of the colon and, in contrast to administration of purified TFF, proved to be very effective in prevention and healing of acute DSS-induced colitis. The in situ secreted murine TFF significantly decreased morbidity and mortality and stimulated prostaglandin-endoperoxide synthase 2 expression, which represents a major therapeutic pathway. In addition, this approach was successful in improving established chronic colitis in IL-10(-/-) mice. CONCLUSIONS: We have positively evaluated a new therapeutic approach for acute and chronic colitis that involves in situ secretion of murine TFF by orally administered L. lactis. This novel approach may lead to effective management of acute and chronic colitis and epithelial damage in humans.     

R-spondin1, a novel intestinotrophic mitogen, ameliorates experimental colitis in mice

BACKGROUND & AIMS: R-spondin 1 (Rspo1) is a novel epithelial mitogen that stimulates the growth of mucosa in both the small and large intestine. METHODS: We investigated the therapeutic potential of Rspo1 in ameliorating experimental colitis induced by dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) as well as nonsteroidal anti-inflammatory drug-induced colitis in interleukin (IL)-10-deficient mice. RESULTS: Therapeutic administration of recombinant Rspo1 protein reduced the loss of body weight, diarrhea, and rectal bleeding in a mouse model of acute or chronic DSS-induced colitis. Histologic evaluation revealed that Rspo1 improved mucosal integrity in both villus and/or crypt compartments in the small intestine and colon by stimulating crypt cell growth and mucosal regeneration in DSS-treated mice. Moreover, Rspo1 significantly reduced DSS-induced myeloperoxidase activity and inhibited the overproduction of proinflammatory cytokines, including tumor necrosis factor-alpha, IL-1alpha, IL-6, interferon-gamma, and granulocyte-macrophage colony-stimulating factor, in mouse intestinal tissue, indicating that Rspo1 may reduce DSS-induced inflammation by preserving the mucosal barrier function. Likewise, Rspo1 therapy also alleviated TNBS-induced interstitial inflammation and mucosal erosion in the mouse colon. Furthermore, Rspo1 substantially decreased the histopathologic severity of chronic enterocolitis by repairing crypt epithelium and simultaneously suppressing inflammatory infiltration in piroxicam-exposed IL-10(-/-) mice. Endogenous Rspo1 protein was localized to villus epithelium and crypt Paneth cells in mouse small intestine. CONCLUSIONS: Our results show that Rspo1 may be clinically useful in the therapeutic treatment of inflammatory bowel disease by stimulating crypt cell growth, accelerating mucosal regeneration, and restoring intestinal architecture.     

Emu Oil Improves Clinical Indicators of Disease in a Mouse Model of Colitis-Associated Colorectal Cancer

Background/Aims

Ulcerative colitis is a remitting and relapsing inflammatory bowel disorder. Current treatments are limited, and if poorly controlled, colitis may progress to colorectal cancer. Previously, Emu Oil protected the intestine in experimental models of gut damage. We aimed to determine whether Emu Oil could reduce the severity of chronic colitis and prevent the onset of neoplasia in a mouse model of colitis-associated colorectal cancer.

Methods

Female C57BL/6 mice were injected (day 0) with azoxymethane, followed by ad libitum access to three dextran sulfate sodium/water cycles (7 days of dextran sulfate sodium and 14 days of water). Mice (n = 9/group) were orally administered either water or Emu Oil (low dose 80 µL or high dose 160 µL), thrice weekly for 9 weeks. Bodyweight and disease activity index were measured daily. Colitis progression was monitored by colonoscopy on days 20, 41 and 62. At killing, tumor number and size were recorded.

Results

Azoxymethane/dextran sulfate sodium induced significant bodyweight loss (maximum 24%) which was attenuated by Emu Oil treatment (low dose days 9, 10, 14: maximum 7%; high dose days 7–15, 30–36: maximum 11%; p < 0.05). Emu Oil reduced disease activity index of azoxymethane/dextran sulfate sodium mice at most time points (maximum 20%; p < 0.05). Additionally, Emu Oil reduced colonoscopically assessed colitis severity (days 20 and 62) compared to disease controls (p < 0.05). Finally, in azoxymethane/dextran sulfate sodium mice, low-dose Emu Oil resulted in fewer small colonic tumors (p < 0.05) compared to controls.

Conclusions

Emu Oil improved clinical indicators and reduced severity of colitis-associated colorectal cancer, suggesting therapeutic potential in colitis management.

     

Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice

AIM: To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium (DSS)-induced acute colitis.METHODS: Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence (NIRF) imaging following intradermal injection of indocyanine green (ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSS administration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin (BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest (ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI.RESULTS: Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels, indicating impaired uptake of a lipid tracer within mesenteric lymphatics. Our in vivo NIRF imaging data demonstrated dilated dermal lymphatic vessels, which were confirmed by immunohistochemical staining of lymphatic vessels, and significantly reduced lymphatic contractile function in the skin of mice with DSS-induced acute colitis. Quantification of the fluorescent intensity remaining in the depot as a function of time showed that there was significantly higher Alexa680-BSA fluorescence in mice with DSS-induced acute colitis compared to pre-treatment with DSS, indicative of impaired lymphatic drainage.CONCLUSION: The lymphatics are locally and systemically altered in acute colitis, and functional NIRF imaging is useful for noninvasively monitoring systemic lymphatic changes during inflammation.     

小鼠葡聚糖硫酸钠结肠炎模型结肠黏膜中5-羟色胺及其转运蛋白的变化和意义

背景：小鼠葡聚糖硫酸钠（DSS）结肠炎模型的组织学特点与人类溃疡性结肠炎（UC）类似。5-羟色胺（5-HT）是胃肠道重要的神经递质，其在UC中的变化和意义鲜见报道。目的：测定小鼠DSS结肠炎模型结肠黏膜中5-HT和5-HT转运蛋白（SERT）的变化，探讨UC是否与5-HT信号转导失衡有关。方法：36只C57BL／6小鼠随机分为急、慢性DSS结肠炎组和正常对照组，以免疫组化方法检测5-HT和SERT的表达，以免疫荧光技术检测SERT的免疫反应性。结果：与正常对照组相比，急、慢性DSS结肠炎组远段和近段结肠黏膜5-HT平均灰度值显著降低（含量增加，P〈0．05），远段结肠黏膜SERT平均灰度值显著增高（含量降低，P〈0．05）。正常对照组、慢性和急性DSS结肠炎组结肠黏膜依次发出耀眼、明亮和微弱的黄绿色荧光，提示DSS结肠炎组SERT免疫反应性减弱。结论：DSS诱导的结肠炎促使小鼠结肠黏膜中5-HT含量和SERT的表达发生变化，5-HT和SERT可能参与了UC发生的病理生理机制。