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Objective: We evaluated the disease modifying effect of simvastatin and atorvastatin in Dextran Sulfate Sodium (DSS) model of colitis.
Materials and methods: Thirty, 8-week old female Swiss-Webster mice were separated into 5 groups (n = 6/group). Colitis was induced by feeding 4
% DSS solution for 7 days. Following discontinuation of DSS, over the next 7 days, the groups orally received simvastatin
(20 mg/kg/day), atorvastatin (60 mg/kg/day), vehicle only (0.75 % methylcellulose), subcutaneous 30 μg injections of anti-TNFα
monoclonal antibody or intraperitoneal anti-mouse apolipoprotein A-I antibody respectively. Disease activity Index (DAI) was
determined daily by a blinded investigator.
Results: The mean reduction in DAI scores from day 7 to day 14 for anti-TNFα group, simvastatin and atorvastatin group were 74 %, 76
% and 64 %, respectively as compared to 41 % reduction in vehicle and anti-apolipoprotein A-I antibodytreated groups.
Conclusions: This finding suggests that statins may have the ability to modify the disease activity in the DSS model of colitis and the
disease modifying effect is comparable to anti-mouse TNFα treatment in this model.
Received 23 October 2006; returned for revision 27 February 2007; accepted by I. Ahnfelt-R?nne 16 August 2007 相似文献
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Effects of ulinastatin in experimental colitis induced by dextran sulfate sodium in rats 相似文献
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Abdelbaqi M Chidlow JH Matthews KM Pavlick KP Barlow SC Linscott AJ Grisham MB Fowler MR Kevil CG 《Laboratory investigation; a journal of technical methods and pathology》2006,86(4):380-390
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders whose etiology remains unknown. Reports have shown that infiltration of leukocytes into intestinal tissue is a pathognomonic hallmark for this disease. Leukocyte beta(2) integrins are heterodimeric adhesion membrane proteins that are exclusively expressed on leukocytes and participate in immune cell adhesion and activation. In this study, we examined the pathophysiological role of the beta(2) integrins CD18, CD11a, and CD11b in the pathogenesis of dextran sodium sulfte (DSS)-induced experimental colitis. Disease activity was measured by daily assessment of clinical parameters including stool consistency, weight loss, occult blood, and gross rectal bleeding. Histopathological changes including severity of inflammation, surface epithelial/crypt damage, and depth of injury were also determined. The CD18 null and CD11a null mice had significantly lower disease activity and cumulative histopathological scores compared to wild-type mice. Interestingly, CD11b null mice did not show protection against DSS colitis and displayed increased disease activity compared to wild-type mice. Examination of specific leukocyte populations in the distal colon from various mice revealed significant attenuation of neutrophil and macrophage infiltrates in CD18, CD11a, and CD11b null mice. Surprisingly, the CD11b null mice showed a significant increase in plasma cell infiltration in response to DSS suggesting that this molecule may influence plasma cell function during colitis. This study demonstrates that genetic loss of CD18 or CD11a is protective during experimental colitis and that CD11b may serve a regulatory role during development of disease. 相似文献
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Suzuki K Sun X Nagata M Kawase T Yamaguchi H Sukumaran V Kawauchi Y Kawachi H Nishino T Watanabe K Yoneyama H Asakura H 《Pathology international》2011,61(4):228-238
Fibrogenic mesenchymal cells including fibroblasts and myofibroblasts play a key role in intestinal fibrosis, however, their precise role is largely unknown. To investigate their role in intestinal fibrosis, we analyzed the lesions of chronic colitis in C57BL/6 (B6) mice induced by dextran sulfate sodium (DSS). B6 mice exposed to single cycle administration of DSS for 5 days developed acute colitis that progressed to severe chronic inflammation with dense infiltrates of mononuclear cells, irregular epithelial structure, thickening of colonic wall, and persistent deposits of collagen. Increased mRNA expressions of proinflammatory cytokines are correlated with extensive cellular infiltration, and the mRNA expressions of collagen 1, transforming growth factor (TGF)-β, and matrix metalloproteinases were also enhanced in the colon. In the colon of chronic DSS colitis, fibroblasts (vimentin(+), α-smooth muscle actin (α-SMA)(-)) were increased in both mucosal and submucosal layers, while myofibroblasts (vimentin(+), α-SMA(+)) were increased in mucosal but not in submucosal layers. Primary mouse subcutaneous fibroblast cultures experiments revealed that exogenously added TGF-β 1 substantially augmented the expressions of both vimentin and α-SMA proteins with increased production of collagen. In conclusion, profibrogenic mesenchymal cells play an important role in the development of intestinal fibrosis in this chronic DSS-induced colitis model. 相似文献
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目的探讨中药青黛对葡聚糖硫酸钠诱导的小鼠溃疡性结肠炎的保护作用及其作用机制。方法 60只SPF级雄性C57BL/6小鼠,体重25-30 g,随机分为对照组(CON组),溃疡性结肠炎组(UC组)、柳氮磺胺吡啶阳性对照组(SASP组)、青黛低剂量组(LQD组)、青黛中剂量组(MQD组)和青黛高剂量组(HQD组),每组10只。利用DSS建立UC模型,采用疾病活动指数评分(DAI)、HE染色、ELISA和Western Blot法评估青黛对溃疡性结肠炎的治疗作用。结果 UC组肠粘膜损伤严重,血浆总TNF-α、IL-6、IL-1、IL-10、MDA含量升高,SOD降低,青黛组可以抑制DSS引发的小鼠溃疡性结肠炎及氧化应激反应,与UC组相比,肠粘膜损伤降低,血浆总TNF-α、IL-6、IL-1、IL-10、MDA含量降低,SOD水平升高,同时Bcl-2蛋白表达水平显著升高,Bax和Caspase3蛋白表达水平明显降低(P0.05),且其作用效果与SASP组没有显著性差异。结论青黛能减轻DSS诱导的小鼠溃疡性结肠炎的炎症反应、氧化应激和细胞凋亡。 相似文献
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Naito Y Takagi T Uchiyama K Kuroda M Kokura S Ichikawa H Yanagisawa R Inoue K Takano H Satoh M Yoshida N Okanoue T Yoshikawa T 《International journal of molecular medicine》2004,14(2):191-196
Interleukin-6 (IL-6) is a multifunctional cytokine secreted by various cells, and is involved in the acute phase response and the immune response through T and B cell activation. To further define the role of IL-6 in intestinal inflammation, we studied the effects of dextran sulfate sodium (DSS) administration in mice with targeted deletions of the IL-6 gene. Acute colitis was induced in female IL-6-/- and IL-6+/+ mice by giving 4.5% DSS orally in drinking water for 8 days. The colonic mucosal injury and inflammation was evaluated based on survival rate, body-weight changes, total colon length and histological findings. Colonic mRNA expression for tumor necrosis factor (TNF)-alpha, IL-6, IL-10 and inducible nitric oxide synthase (iNOS) was measured by RT-PCR. Colonic IL-6 mRNA levels of wild-type mice continued to increase throughout the study period. At each assessment, colonic injury was significantly attenuated in DSS-treated IL-6-/- mice compared with DSS-treated IL-6+/+ mice. Histological study also showed a reduced infiltration of inflammatory cells, especially neutrophils, and mucosal cell disruption in DSS-treated IL-6-/- mice compared with DSS-treated IL-6+/+ mice. In the colons of DSS-treated IL-6-/- mice, the expression of both TNF-alpha mRNA and iNOS mRNA was reduced on day 5. In contrast, IL-10 mRNA expression was enhanced compared with DSS-treated IL-6+/+ mice. In conclusion, DSS-induced inflammation appears to be significantly inhibited in IL-6-/- mice compared to wild-type mice. These data suggest that persistent and marked blockade of IL-6 bioactivity provides some beneficial effects on intestinal inflammation. 相似文献
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Intravenous immunoglobulin (IVIG) treatment of experimental colitis induced by dextran sulfate sodium in rats 总被引:2,自引:0,他引:2 下载免费PDF全文
N SHINTANI T NAKAJIMA H NAKAKUBO H NAGAI Y KAGITANI H TAKIZAWA H ASAKURA 《Clinical and experimental immunology》1997,108(2):340-345
We investigated the therapeutic effect and immunological action mechanism of IgG in experimental colitis induced by 3% dextran sulfate sodium in rats. Intravenous injection of homologous (rat) IgG (400 mg/kg per day) caused a significant suppression of occult blood discharge and ulcerative lesions in the colon, while no suppressive effect was observed in the case of heterologous (human) IgG. The positive effect of rat IgG on the lesions was also clearly shown by the histological examinations. Generation of proinflammatory cytokines, i.e. tumour necrosis factor-alpha (TNF-α) and IL-1α, in the lesions was found to be inhibited by administration of rat IgG. Little or no suppressive action was exerted by human IgG. Careful examination of recruited T cells and macrophages, both of which are thought to play important roles in the development of ulcerative colitis, indicated that rat IgG, but not its human counterpart, decreased the number of immunocompetent cells in colonic mucosa. Meanwhile, in an in vitro study, both forms of IgG were shown to suppress production of TNF-α and IL-1α from lamina propria mononuclear cells isolated from rat colon. These findings suggest that, mainly by suppressing recruitment of immunocompetent cells into the lesions, homologous IgG may reduce the occurrence of colitis. 相似文献
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《中国病理生理杂志》2001,(9)
The effects of ulinastatin in experimental colitis induced by dextran sulfate sodium (DSS) in rats 相似文献
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Choi YA Kang OH Park HJ Tae J Kim DK Kang CS Choi SC Yun KJ Choi SJ Nah YH Kim YH Bae KH Lee YM 《International journal of molecular medicine》2005,16(4):667-672
Scutellaria baicalensis Georgi (Labiatae) has been used in the treatment of inflammatory diseases. Drug processing (Poje) is the process of treating crude drugs by several methods before use. The aim of this study was to determine the effect of processed Scutellaria baicalensis on experimental ulcerative colitis induced by dextran sulfate sodium (DSS). The types of processed Scutellaria baicalensis used in this study were parched Scutellaria baicalensis (PS) and rice wine-baked Scutellaria baicalensis (RWBS). Experimental colitis was induced in mice using a daily treatment of 5% DSS in the drinking water for 7 days. The water extracts of processed Scutellaria baicalensis (1 g/kg) were administered orally once a day for 7 days. The mice were divided in four groups: i) water plus DSS group, ii) crude Scutellaria baicalensis (CS) plus DSS group, iii) PS plus DSS group, and iv) RWBS plus DSS group. RWBS ameliorated all of the inflammatory symptoms, such as body weight loss, rectal bleeding and histological damage, compared to CS. Furthermore, RWBS significantly reduced the mucosal myeloperoxidase activity, and TNF-alpha (tumor necrosis factor-alpha), COX-2 (cyclooxygenase-2), NF-kappaB (nuclear factor-kappa B) and chymase expression more than CS. But these effects were not shown in the PS plus DSS group. Efficacy of Scutellaria baicalensis was increased after rice wine baking, but not after parching. The findings in this study suggest that RWBS may be a useful therapeutic agent for ulcerative colitis. 相似文献
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This study aimed to explore the effects of neoagarotetraose (NAT) on gut microbiota composition and inflammation after antibiotic treatment. Our results showed that NAT significantly increased the length of colon (P?.01) and decreased the ileocecal valve index (P?.05), and reduced IFN-γ content (P?.01) and downregulated the IFN-γ/IL-4 ratio (P?.01), suggesting that NAT mediated the balance of the Th1/Th2 ratio to maintain the immune equilibrium of the intestinal mucosa. Our data showed that NAT prohibited intestinal inflammation by increasing antimicrobial peptides and gut integrity. Furthermore, NAT administration significantly increased the fecal concentration of total short-chain fatty acids. In addition, NAT had the ability to modulate gut microbiota composition and diversity. In our study, significantly increased Bifidobacterium, Lactobacillus and Prevotella were observed in the NAT group (P?.01). In summary, all of these results demonstrated that NAT was a potential prebiotic for modulating intestinal microbiota and promoting host health. 相似文献
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The anti-inflammatory effect of berberine was evaluated in murine model of acute experimental colitis induced by dextran sulfate sodium (DSS). Berberine, given orally at 40, 20, 10?mg/kg for 10 days, ameliorated all the supposed inflammatory symptoms of the induced colitis, such as body weightloss, blood hemoglobin reduction, high myeloperoxidase levels, and malondialdehyde content-inflamed mucosa. Furthermore, the cytokine production of splenic lymphocytes was analyzed. The results showed the IFN-γ and IL-12 were increased, but IL-4 and IL-10 were decreased in DSS-induced colitis,when those were compared with the normal control. But the administration of berberine to DSS-induced colitis mice showed lower production of IFN-γ and IL-12 and higher production of IL-4 and IL-10 than the DSS-induced colitis mice. The results suggest that the protective effects of berberine against the DSS-induced colitis may be associated with the regulation of cytokine production. 相似文献
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《Immunopharmacology and immunotoxicology》2013,35(3):391-397
The anti-inflammatory effect of berberine was evaluated in murine model of acute experimental colitis induced by dextran sulfate sodium (DSS). Berberine, given orally at 40, 20, 10?mg/kg for 10 days, ameliorated all the supposed inflammatory symptoms of the induced colitis, such as body weightloss, blood hemoglobin reduction, high myeloperoxidase levels, and malondialdehyde content-inflamed mucosa. Furthermore, the cytokine production of splenic lymphocytes was analyzed. The results showed the IFN-γ and IL-12 were increased, but IL-4 and IL-10 were decreased in DSS-induced colitis,when those were compared with the normal control. But the administration of berberine to DSS-induced colitis mice showed lower production of IFN-γ and IL-12 and higher production of IL-4 and IL-10 than the DSS-induced colitis mice. The results suggest that the protective effects of berberine against the DSS-induced colitis may be associated with the regulation of cytokine production. 相似文献
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Signal‐transducing adaptor protein‐2 regulates macrophage migration into inflammatory sites during dextran sodium sulfate induced colitis 下载免费PDF全文
Natsuko Fujita Kenji Oritani Michiko Ichii Takafumi Yokota Norimitsu Saitoh Daisuke Okuzaki Yuichi Sekine Shigeyuki Kon Ryuta Muromoto Kodai Saitoh Akihiko Yoshimura Tadashi Matsuda Yuzuru Kanakura 《European journal of immunology》2014,44(6):1791-1801
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Objective and design: Myeloperoxidase (MPO) and proinflammatory cytokines play an important role in the development of inflammation. These markers
are generally measured using tedious ELISA procedures. In this study, a novel technique utilizing antibody conjugated quantum
dot nanoparticles was developed to detect Myeloperoxidase, Interleukin-1α (IL-1α) and Tumor Necrosis Factor-α (TNF-α) in vivo in the dextran sodium sulfate (DSS) model of experimental colitis.
Materials and methods: Colitis was induced in animals (n = 8 animals/group) by feeding 4% DSS solution ad libitum for seven to eight days. Quantum Dots (QDs) exhibiting fluorescence at various wavelengths were conjugated to MPO, IL-1α
and TNF-α polyclonal antibodies and tested in vivo at various stages of colitis. Tissue sections obtained were imaged with confocal microscope. The image intensity obtained
from the tissue specimen was correlated with clinical activity measured as Disease Activity Index (DAI).
Results: Myeloperoxidase, IL-1α and TNF-α were visualized with quantum dots on various days of disease. The intensity of quantum dots
increased with the increase in inflammation. The increase in intensity showed an excellent correlation with the DAI based
on the clinical parameters.
Conclusion: The study demonstrated that multiple biomarkers can be detected simultaneously and their quantitative expression correlated
well with clinical disease severity. This novel technology should facilitate design of a novel optical platform for imaging
various biomarkers of inflammation, early detection of acute and chronic disease markers and inflammation-mediated cancer
markers. This detection may also facilitate determination of therapeutic success.
Received 14 March 2007; returned for revision 8 May 2007; accepted by M. Parnham 27 June 2007 相似文献