氧化苦参碱对葡萄糖硫酸钠诱导结肠炎影响的初步研究

目的：探讨氧化苦参碱（OM）对大鼠溃疡性结肠炎（UC）的保护作用。方法：用葡聚糖硫酸钠（DSS）诱导大鼠结肠炎，对比OM组、DSS对照组和正常对照组的疾病活动度（DAI）及病理学评分。结果：两项指标在3组间均存在显著差异（P＜0．05）。结论：OM能够减轻DSS诱导的结肠炎症状和肠粘膜损害。     

氧化苦参碱对葡聚糖硫酸钠诱导大鼠结肠炎的抗炎作用机制研究

目的　探讨氧化苦参碱 (OM )对葡聚糖硫酸钠 (DSS)诱导结肠炎的抗炎作用及其作用机制。方法　建立DSS诱导的大鼠结肠炎模型。SD大鼠 2 6只 ,随机分为OM处理组 (A组 ,10只 )、OM未处理组 (B组 ,10只 )和正常对照组 (C组 ,6只 )。A组第 1～ 11天肌内注射OM 6 3mg·kg-1·d-1,第 4～ 11天饮用 2 %DSS溶液 ;B组第 1～ 11天肌注与A组OM等体积的生理盐水 ,第 4～ 11天饮用 2 %DSS溶液 ;C组肌注生理盐水同B组 ,正常饮水。观察大鼠的腹泻、便血症状及结肠组织学改变 ,ELISA测定血清肿瘤坏死因子 α(TNF α)和白细胞介素 6 (IL 6 )水平 ,免疫组化检测结肠黏膜核转录因子 κB(NF κB)活性及细胞间粘附分子 1(ICAM 1)的表达。结果　与OM未处理组相比 ,OM处理组大鼠的症状和结肠黏膜组织学损伤显著改善 (P值均 <0 .0 5 ) ,TNF α ,IL 6 ,NF κB和ICAM 1显著降低 (P值均 <0 .0 5 )。结论　OM可抑制NF κB活化 ,降低TNF α、IL 6和ICAM 1的生成 ,从而减轻结肠炎性损伤和腹泻、便血症状。     

葡聚糖硫酸钠诱导大鼠结肠炎发病机制的研究

背景:葡聚糖硫酸钠(DSS)可诱导大鼠结肠炎,但其发病机制尚不完全清楚。目的:探讨DSS诱导大鼠结肠炎的发病机制。方法:16只健康雄性Sprague-Dawley大鼠随机分成DSS模型组(10只)和正常对照组(6只),DSS模型组大鼠自由饮用2％DSS溶液8天,正常对照组大鼠正常饮水。于第9天处死大鼠,采用酶联免疫吸附测定(ELISA)方法测定血清肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6水平,采用免疫组化方法测定结肠黏膜细胞间黏附分子(ICAM)-1的表达和核因子(NF)-κB活性。结果:DSS模型组大鼠出现腹泻、便血以及结肠黏膜糜烂或溃疡,血清TNF-α和IL-6水平以及结肠黏膜ICAM-1表达和NF-κB活性均较正常对照组显著增高(P<0.01)。结论:在DSS诱导的大鼠结肠炎中,DSS可能通过活化NF-κB使TNF-IL-6和ICAM-1生成增加,导致结肠黏膜炎性损害和腹泻、便血。     

肠内营养对DSS诱导的溃疡性结肠炎大鼠肠道通透性的影响

目的研究肠内营养对溃疡性结肠炎大鼠肠黏膜通透性的影响。方法将40只大鼠随机分为4组,正常对照组、模型对照组、甲泼尼龙组、谷氨酰胺组,后3组大鼠自由饮用5%DSS溶液7天,建立溃疡性结肠炎模型,后2组同时分别给予甲泼尼龙及谷氨酰胺干预治疗。收集大鼠24h尿液,采用高效液相色谱分析法研究大鼠肠道通透性的情况。结果 DSS诱导的溃疡性结肠炎大鼠乳果糖尿中排出率显著增高(P0.01),甘露醇尿中排出率下降(P0.01),L/M比值在DSS诱导的溃疡性结肠炎大鼠显著增加(P0.01)。与DSS诱导的溃疡性结肠炎模型组比较,甲泼尼龙组大鼠及谷氨酰胺组大鼠乳果糖尿中排出率下降(P0.01),甘露醇尿中排出率升高(P0.01),L/M比值降低(P0.01);谷氨酰胺组较甲泼尼龙组变化明显,但两组比较无显著差异(P0.05)。结论溃疡性结肠炎大鼠结肠黏膜通透性增加,给予肠内营养可降低结肠黏膜通透性。     

小檗碱对老龄大鼠葡聚糖硫酸钠所致结肠炎黏膜组织结构及相关炎症因子表达的影响

目的 探讨小檗碱(Ber)对葡聚糖硫酸钠(DSS)诱导结肠炎老年大鼠的疗效及其可能的机制. 方法 以DSS饮水法复制18月大鼠实验性结肠炎30只, 随机平均分为3组:正常对照组、结肠炎模型(DSS)组和Ber治疗(DSS+Ber)组.观察Ber对疾病活动指数(DAI)和结肠黏膜结构及肿瘤坏死因子α(TNF-α)、核转录因子кB (NF-кB)、细胞间黏附分子-1(ICAM-1)、诱生型一氧化氮合酶(iNOS)表达的影响. 结果 给予DSS后老龄大鼠出现典型的结肠炎的变化.Ber治疗可显著降低结肠炎老龄大鼠的DAI评分[(1.862±0.623)分比(2.317±0.729)分,P ＜0.05]和组织学病理评分[(1.347±0.548)分比(1.945±0.853)分,P＜0.05].Ber治疗显著降低肠组织TNF-α[(832.5±178.8 ) pg/g比(1438.2±312.5) pg/g,P＜0.05],并降低黏膜组织NF-κB[(0.154±0.623)比(0.213±0.058),P＜0.05], ICAM-1[(0.124±0.076)比(0.156±0.101),P＜0.05]和iNOS(0.098±0.048比0.125±0.053,P＜0.05). 结论 Ber可治疗老龄大鼠的DSS结肠炎, 其降低肠组织TNF-α、IL-1β和IL-6 mRNA的表达可能是其疗效机制之一.     

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。     

金丝桃苷对葡聚糖硫酸钠诱导小鼠结肠炎Nrf2/ARE信号通路的作用

目的探讨金丝桃苷(Hyperoside,Hyp)对葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠肠黏膜Nrf2/ARE信号通路的影响。方法用DSS诱导结肠炎小鼠模型,实验设对照组、模型组、DSS+Hyp低剂量组(DSS+Hyp 80 mg/kg)、DSS+Hyp高剂量组(DSS+Hyp 120 mg/kg),每组6只;质量浓度为30 g/L的DSS自由饮水7 d制成结肠炎小鼠模型同时于造模前7 d开始予Hyp灌胃治疗,连续14 d。观察小鼠结肠炎疾病活动指数(DAI)和结肠组织病理变化,Western blotting法检测小鼠结肠组织细胞核核转录因子(Nuclearfactor-erythroid 2-rdated factor-2,Nrf-2)表达水平,RT-PCR检测小鼠结肠组织Nrf-2、超氧化物歧化酶(SOD)表达水平。结果与模型组比较,对照组、Hyp+DSS诱导组的结肠炎小鼠DAI降低(P0.01)。Hyp能够明显改善结肠病理损伤。与模型组比较,Hyp明显提高Nrf2的表达(P0.05)。对照组、Hyp+DSS诱导组小鼠结肠SOD mRNA的相对表达量与模型组比较显著升高(P0.05)。结论 Hyp对DSS诱导的结肠炎小鼠模型有保护作用,其作用机制可能与Nrf2/ARE信号通路有关。     

肝素治疗右旋葡聚糖硫酸钠诱导小鼠结肠炎的疗效观察

目的　评价肝素预防及治疗右旋葡聚糖硫酸钠 (DSS)诱导小鼠结肠炎的有效性。方法　32只小鼠中 ,16只正常小鼠分成两组 ,饮用DSS 7d的同时预防组皮下注射肝素 ,对照组皮下注射生理盐水 ;另 16只饮用DSS 7d后诱导结肠炎的小鼠分成两组 ,治疗组皮下注射肝素 ,对照组皮下注射生理盐水。用疾病活动指数、组织学评分、TNF α的表达和马休斯猩红兰 (MSB)检测微血栓评价疗效。结果　肝素在预防组降低微血栓的形成 ,对照组 8只中 4只微血栓阳性 ,预防组均阴性 (P =0 .0 38)。治疗组组织学评分、TNF α的表达明显降低 ,治疗组与对照组的直肠、横结肠组织学评分和TNF α的表达分别为 1.33和 1.85 (P <0 .0 5 ) ,0 .92和 1.6 8(P <0 .0 5 ) ,(5 .5± 3.5 ) %和 (10 .8± 4.2 ) % (P <0 .0 5 )。结论　肝素可抑制DSS诱导结肠炎小鼠血栓形成和结肠炎症 ,实验结果提示肝素用于溃疡性结肠炎治疗也可能有效     

DSS、TNBS、OXZ诱导结肠炎动物模型的对比

目的 对比研究DSS、TNBS、OXZ诱导的结肠炎动物模型.方法 本研究选取了一般状态、DAI评分和组织学损伤评分几个方面来评价.结果 DSS组大鼠造模安全性较高,在整个实验过程中无大鼠出现死亡,而TNBS组及OXZ组均有2只大鼠出现死亡,DSS组大鼠DAI评分升高较快,于实验第7天时各模型组DAI评分差异无统计学意义,TNBS组组织学损伤最重,但各造模组之间差异无统计学意义.结论 三种造模方法均可以成功诱导大鼠实验性结肠炎模型,各造模组DAI评分和组织学损伤没有显著的差异.DSS造模方法具有较高的安全性.     

DSS与TNBS诱导大鼠实验性结肠炎模型的对比研究

背景:鉴于人体实验受到诸多限制,建立、选择合适的动物模型对于溃疡性结肠炎(UC)的研究具有重要意义。目的:比较葡聚糖硫酸钠(DSS)和三硝基苯磺酸(TNBS)诱导的大鼠实验性结肠炎模型的症状和结肠病理改变,以期为UC相关研究动物模型的选择提供参考。方法:予Sprague-Dawley大鼠自由饮用4%DSS 7 d或予100 mg/kg TNBS-50%乙醇单次灌肠建立实验性结肠炎模型,动态评估疾病活动指数(DAI)。分批取模型大鼠全结肠标本,观察不同时点的结肠损伤评分、髓过氧化物酶(MPO)活性等指标。结果:DSS和TNBS模型组DAI最高值分别出现在实验第7天和第2天,其后呈下降趋势,两组造模过程中分别有6只和1只大鼠死亡。DSS模型组结肠炎症持续时间短,损伤轻,停药后病变逐渐好转,18 d时结肠损伤评分和MPO活性分别为0.25±0.50和(0.80±0.33)U/g,与正常对照组相比无明显差异。TNBS模型组结肠炎症持续时间长,损伤重,21 d时结肠损伤评分和MPO活性分别为3.60±0.55和(1.60±0.39)U/g,组织学上呈现慢性炎症特征。结论:DSS和TNBS均可成功诱导大鼠实验性结肠炎模型,后者可体现急性炎症向慢性转化的动态过程,可能更适用于UC治疗相关研究。     

Low-dose oral ferrous fumarate aggravated intestinal inflammation in rats with DSS-induced colitis

BACKGROUND: Oral ferrous iron therapy may reinforce intestinal inflammation. One possible mechanism is by catalyzing the production of reactive oxygen species. We studied the effects of low-dose oral ferrous fumarate on intestinal inflammation and plasma redox status in dextran sulfate sodium (DSS)-induced colitis in rats. METHODS: Forty male Wistar rats were divided into 5 groups: no intervention, sham gavage (distilled water), ferrous fumarate, DSS, and ferrous fumarate + DSS. Ferrous fumarate was dissolved in distilled water (0.60 mg Fe/kg per day) and administered by gavage on days 1 to 14. All rats were fed a standard diet. Colitis was induced by 5% DSS in drinking water on days 8 to 14. Rats were killed on day 16. Histologic colitis scores, fecal granulocyte marker protein, plasma malondialdehyde, plasma antioxidant vitamins, and plasma aminothiols were measured. RESULTS: DSS significantly increased histologic colitis scores (P < 0.001) and fecal granulocyte marker protein (P < 0.01). Ferrous fumarate further increased histologic colitis scores (P < 0.01) in DSS-induced colitis. DSS + ferrous fumarate decreased plasma vitamin A compared with controls (P < 0.01). Otherwise, no changes were seen in plasma malondialdehyde, plasma antioxidant vitamins, or plasma aminothiols. CONCLUSION: Low-dose oral ferrous iron enhanced intestinal inflammation in DSS-induced colitis in rats.     

Vanilloid receptor-1 containing primary sensory neurones mediate dextran sulphate sodium induced colitis in rats

BACKGROUND AND AIMS: The role of sensory neurones in colitis was studied by chemical denervation of primary sensory neurones as well as antagonism of the vanilloid receptor-1 (VR-1) in rats prior to administration of dextran sulphate sodium (DSS) to induce colitis. METHODS: Neonatal rats were chemically denervated by subcutaneous administration of capsaicin; controls received capsaicin vehicle only. When animals reached maturity, colitis was induced by administration of 5% DSS in drinking water for seven days. Additionally, normal adult rats were treated with a VR-1 antagonist capsazepine (CPZ) or vehicle twice daily via an enema from day 0 to day 6 of the DSS regimen. Control rats were treated with an enema infusion of vehicle and 5% DSS, or without either an enema infusion or DSS in drinking water. For both groups of rats, severity of inflammation was quantitated by disease activity index (DAI), myeloperoxidase (MPO) activity, and histological examination. RESULTS: DSS induced active colitis in all control rats with resultant epithelial ulceration, crypt shortening, and neutrophil infiltration. Both neonatal capsaicinised rats and normal adult rats treated with CPZ enemas exhibited significantly lower levels of DAI, MPO, and histological damage compared with vehicle treated rats (p< 0.05). CONCLUSIONS: Neonatal capsaicinisation and local administration of CPZ prevents intestinal inflammation in a well established model of colitis indicating that primary sensory neurones possessing VR-1 receptors are required in the propagation of colonic inflammation.     

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.     

肥大细胞及类胰蛋白酶在溃疡性结肠炎大鼠结肠黏膜中的表达

目的:观察类胰蛋白酶抑制剂甲磺酸卡萘司他(NM)对肥大细胞(MC)数量和类胰蛋白酶表达及血清IL-6、IL-8含量的影响.方法:40只♂Wistar大鼠按1∶3随机分为空白对照组(A组)和研究组(S组),造模成功后S组再随机分为3组,并以不同溶液灌肠:B组(模型对照组,无菌蒸馏水)、C组(NM组,10-9mol/LNM)、D组[5-氨基水杨酸(5-ASA)组,100mg/kg5-ASA].以免疫组织化学方法检测远端结肠黏膜MC类胰蛋白酶的表达变化,以ELISA法检测动物血清中IL-6、IL-8的表达变化.结果:(1)治疗第1天,A组DAI评分与B、C、D组相比,差异有显著统计学意义(P<0.01);实验结束后,B组DAI、HI评分与C、D组相比明显增高(DAI:6.25±1.67vs3.63±1.30,2.75±0.71;HI:5.10±0.74vs2.30±0.67,2.00±0.82;均P<0.01);(2)B组远端结肠黏膜MC数显著高于C、D组(MC:13.25±1.67vs6.37±1.19,5.00±1.07,均P<0.05).B组类胰蛋白酶表达量显著低于C、D组(119.22±9.85vs150....     

Kefir treatment ameliorates dextran sulfate sodium-induced colitis in rats

AIM: To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium(DSS) in rats.METHODS: Twenty-four male Wistar-albino rats were randomized into four groups: normal control,kefircontrol,colitis,and kefir-colitis groups. Rats in the normal and kefir-control groups were administered tap water as drinking water for 14 d. Rats in the colitis and kefir-colitis groups were administered a 3% DSS solution as drinking water for 8-14 d to induce colitis. Rats in the kefir-control and kefir-colitis groups were administered 5 m L kefir once a day for 14 d while rats in the normal control and colitis group were administered an identical volume of the placebo(skim milk) using an orogastric feeding tube. Clinical colitis was evaluated with reference to the disease activity index(DAI),based on daily weight loss,stool consistency,and presence of bleeding in feces. Rats were sacrificed on the 15 th day,blood specimens were collected,and colon tissues were rapidly removed. Levels of myeloperoxidase(MPO),tumor necrosisfactor(TNF)-α,interleukin(IL)-10,malondialdehyde,and inducible nitric oxide synthase(i NOS) were measured in colon tissue.RESULTS: The DAI was lower in the kefir-colitis group than in the colitis group(on the 3rd and 5th days of colitis induction; P 0.01). The DAI was also significantly higher in the colitis group between days 2 and 6 of colitis induction when compared to the normal control and kefir-control groups. The DAI was statistically higher only on the 6th day in the kefircolitis group when compared to that in the normal control groups. Increased colon weight and decreased colon length were observed in colitis-induced rats. Mean colon length in the colitis group was significantly shorter than that of the kefir-control group. Kefir treatment significantly decreased histologic colitis scores(P 0.05). MPO activity in the colitis group was significantly higher than in the kefir-control group(P 0.05). Kefir treatment significantly reduced the DSS colitis-induced TNF-α increase(P 0.01). No statistically significant differences were observed among groups for IL-10 and MDA levels. Colon tissue i NOS levels in the colitis group were significantly higher than those in the control and kefir-colitis groups(P 0.05).CONCLUSION: Kefir reduces the clinical DAI and histologic colitis scores in a DSS-induced colitis model,possibly via reduction of MPO,TNF-α,and i NOS levels.     

Therapeutic effect of phenantroline in two rat models of inflammatory bowel disease.

BACKGROUND: Phenantroline is a zinc-chelator that inhibits biological activities of matrix metalloproteinases (MMPs). Over-expression of MMPs can accelerate tissue destruction and disrupt subsequent tissue repair. The effects of phenantroline in two rat models of inflammatory bowel disease (IBD) are evaluated: transmural colitis induced by trinitrobenzensulphonic acid (TNBS) and distal colitis caused by dextran sulphate sodium (DSS). METHODS: Transmural colitis was induced by TNBS in two groups of 15 rats each, and distal colitis was induced by DSS in two other groups of 15 rats each. Phenantroline was administered by oral gavage at 20 mg kg(-1) day(-1) to the test groups, whereas matched control groups received oral vehicle. On the last day of dosing, rats were subjected to intracolonic dialysis under anaesthesia for assessment of luminal eicosanoid release (PGE2, TXB2 and LTB4) and euthanized. Colons were removed and lesions were blindly scored according to macroscopic and histological scales. Myeloperoxidase (MPO) activity was measured in homogenates of colonic tissue. RESULTS: In the TNBS model, phenantroline treatment significantly reduced colonic strictures; in the DSS model, phenantroline significantly decreased scores of epithelial injury. In both models, the levels of PGE2, TXB2 and LTB4 and tissue MPO were not significantly altered. CONCLUSIONS: Although phenantroline did not modify the activity of inflammatory mediators, this compound substantially reduced intestinal injury associated with tissue remodelling.     

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.     

Anti-inflammatory mechanism of oxymatrine in dextran sulfate sodium-induced colitis of rats

AIM: To investigate the anti-inflammatory mechanism of oxymatrine in dextran sulfate sodium (DSS)-induced colitis of rats. METHODS: Acute colitis was induced by giving 2% DSS orally in drinking water for 8 d. Twenty-six male rats were randomized into oxymatrine-treated group (group A, 10 rats), DSS control (group B, 10 rats) and normal control (group C, 6 rats). The rats in group A were injected muscularly with oxymatrine at the dosage of 63 mg/(kg·d) from d 1 to 11 and drank 2% DSS solution from d 4 to 11. The rats in group B were treated with 0.9% saline in an equal volume as group A and drank 2% DSS solution from d 4 to 11. The rats in group C were treated with 0.9% saline as group B from d 1 to 11 and drank water normally. Diarrhea and bloody stool as well as colonic histology were observed. The levels of serum tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) were determined by ELISA, and nuclear factor-κB (NF-κB) activity and the expression of inter-cellular adhesion molecule-1(ICAM-1) in colonic mucosa were detected by immunohistochemistry method. RESULTS: Compared with DSS contror group, the inflammatory symptoms and histological damages of colonic mucosa in oxymatrine-treated group were significantly improved, the serum levels of TNF-α, IL-6, and the expression of NF-κB, ICAM-1 in colonic mucosa were significantly reduced. CONCLUSION: The fact that oxymatrine can reduce the serum levels of TNF-α, IL-6, and the expression of NF-κB and ICAM-1 in colonic mucosa in DSS-induced colitis of rats indicates that oxymatrine may ameliorate the colonic inflammation and thus alleviate diarrhea and bloody stool.     

Predominance of caecal injury in a new dextran sulphate sodium treatment in rats: histopathological and fermentative characteristics

OBJECTIVES : Cyclic administrations of dextran sulphate sodium (DSS) alternating with distilled water usually induce chronic colitis after a few weeks. In order to obtain stable chronic colitis (without recovery or relapse) in a few days, a new continuous DSS treatment was tested and characterized. Short-chain fatty acids (SCFAs), which remain poorly documented in experimental colitis, were also investigated. METHODS : Thirty-six Sprague-Dawley rats were treated with 5% DSS for 7 days (DI) followed by 3% DSS for 7 days (DM) or 14 days (DF). Control rats received only water. Inflammatory injuries in the caecum and the colon were assessed by macroscopic (colon length, caecum weight, damages score) and histological parameters. SCFAs (acetate, propionate, butyrate) were quantified individually in caecal, proximal and distal contents. RESULTS : Macroscopic and histological observations revealed that this continuous DSS treatment induced acute inflammation (DI) followed rapidly by chronic active colitis. The latter was uncommonly predominant in the caecum and the distal colon, and was also associated with some fermentative disturbances. Caecal SCFA concentrations decreased with DSS at DI and DM. The molar ratio of caecal butyrate increased with DSS. Acetate decreased in the colon while propionate increased. CONCLUSION : This new DSS treatment is able to induce in a few days stable chronic inflammation with caecal and distal predominant injuries, and mild fermentative caeco-colonic alterations. This model could contribute to the study of potential anti-inflammatory effects of prebiotics.     

Oxidative stress and metabolism in animal model of colitis induced by dextran sulfate sodium

BACKGROUND AND AIM: Ulcerative colitis is a chronic inflammatory disease of the gastrointestinal tract. Its etiology remains unclear, but it appears to result from a dysregulated immune response, with infiltration of phagocytic leukocytes into the mucosal interstitium. The production and release of reactive oxygen species by immune cells seems to play a crucial role in physiopathology of colitis. The aim of this work was to evaluate the effects of N-acetylcysteine (NAC) and deferoxamine (DFX) in the treatment of colitis induced by dextran sulfate sodium (DSS). METHODS: The effects of NAC and DRX on rats with DSS-induced colitis were determined by measuring intestinal parameters of oxidative stress and mitochondrial function, inflammatory response and bowel histopathological alterations. RESULTS: DSS increased white blood cells count and NAC and DFX did not prevent this effect. However, DSS increased mitochondrial respiratory chain complex IV in colon of rats and NAC and DFX prevented this alteration. In addition, thiobarbituric acid reactive substances were increased in colon of DSS-treated rats. NAC and DFX, when taken together, prevented this effect. Complex II and succinate dehydrogenase were not affected by DSS, as protein carbonyl content. CONCLUSIONS: It is speculated that NAC and DFX might be useful for treatment of colitis, but further research is necessary to clarify these effects.