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     

Met-RANTES干预实验性小鼠溃疡性结肠炎对MIP-3α及其受体CCR6的影响

目的:探讨MIP-3α及其受体CCR6在实验性小鼠溃疡性结肠炎(UC)发病中的作用,并分析Met-RANTES疗效机制.方法:用葡聚糖硫酸钠(DSS)诱导建立结肠炎小鼠模型,观察Met-RANTES对小鼠结肠炎病活动指数(DAI)、大体形态评分(GMS)、结肠组织学病理评分(HPS)的影响:并通过RT-PCR检测其对小鼠结肠组织MIP-3α、CCR6mRNA的表达变化及Western blot和免疫组织化学方法检测其小鼠结肠组织MIP-3α、CCR6的蛋白表达变化.结果:DAI、GMS和HPS在DSS模型组和生理盐水治疗组中高于空白对照组,MIP-3α和CCR6在小鼠溃疡性结肠炎中表达上调,在小鼠空白对照组中不表达或弱阳性表达,差异有统计学意义(P<0.01):与DSS模型组和生理盐水治疗组相比,Met-RANTES治疗组小鼠DAI、GMS和HPS降低,MIP-3α和CCR6表达下调(mRNA:0.21±0.08 vs 1.09±0.08.1.08±0.07;0.25±0.08 vs 1.11±0.07,1.05±0.08,P<0.01:蛋白:0.28±0.08 vs 0.98±0.07,1.05±0.06;0.25±0.07 vs 1.19±0.07.1.15±0.06.P<0.01):生理盐水治疗组小鼠DAI、GMS和HPS 以及MIP-3α和CCR6表达与DSS模型组相比表达无明显差异(P>0.05).结论:MIP-3α与CCR6参与了小鼠UC的发生、发展;Met-RANTES能下调MIP-3α及CCR6的表达,并能减轻炎症损伤;针对MIP-3α或CCR6的靶向治疗可能是UC一种有效的治疗方法.     

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。     

趋化因子CCL20及其受体CCR6在实验性结肠炎小鼠中的表达及其意义

背景：溃疡性结肠炎（UC）的病因和发病机制尚不完全明确，趋化因子异常可能在其发生、发展中起重要作用。目的：研究趋化因子CCL20及其受体CCR6在葡聚糖硫酸钠（DSS）诱导的实验性结肠炎小鼠结肠黏膜中的表达以及CCL20与CCR6的相关性，探讨两者在结肠炎发病机制中的作用。方法：30只雌性BALB／c小鼠分为对照组和模型组。模型组小鼠自由饮用5％DSS溶液7d，建立实验性结肠炎模型；对照组小鼠自由饮用蒸馏水7d。第8d处死小鼠，观察疾病活动指数（DAI）、结肠组织学评分。以逆转录聚合酶链反应（RT．PCR）检测小鼠结肠黏膜CCL20、CCR6mRNA表达，以免疫组化和蛋白质印迹法检测结肠黏膜CCL20、CCR6蛋白表达，并分析CCL20与CCR6的相关性。结果：模型组DAI和结肠组织学评分均显著高于对照组（P〈0．01）；CCL20、CCR6mRNA和蛋白表达显著高于对照组（P〈0．01），且与结肠炎症程度呈正相关。CCL20mRNA表达与CCR6mRNA表达有明显相关性（r＝0．763．P=0．000071）。结论：CCL20和CCR6表达参与了结肠炎的发生和发展，两者相互作用可能在结肠炎局部结肠组织破坏和病理变化中起重要作用，有望成为UC的潜在治疗靶点。     

氧化苦参碱对葡聚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.     

嗜酸乳杆菌和青春双歧杆菌治疗实验性结肠炎小鼠的作用及其机制

目的 评价青春双歧杆菌和嗜酸乳杆菌对实验性结肠炎小鼠模型的治疗效果并初步探讨其机制.方法 75只BABL/C小鼠均分为5组并给予相应处理,其中4组为实验组,分别为:青春双歧杆菌BF0624治疗组(B组)、嗜酸乳杆菌LT0637治疗组(L组)、水杨酸柳氮磺胺吡啶治疗组(S组)、0.9%氯化钠对照组(NS组);另设正常对照组(N组).实验组小鼠用4%葡聚糖硫酸钠造模,N组则饮用0.9%氯化钠溶液.实验期间每天记录动物体重、大便隐血情况,计算疾病活动指数(DAI).在第4、6、8天各组各处死5只小鼠,分离结肠,测量其长度,行病理组织学检查,逆转录PCR和Western印迹法分别测定热休克蛋白(HSP)70、糖皮质激素受体(GR)、白细胞介素(IL)-10和肿瘤坏死因子(TNF)-α的基因和蛋白表达.结果 青春双歧杆菌BF0624和嗜酸乳杆菌LT0637能缓解实验性结肠炎小鼠的肠道炎性反应,第3天时L组小鼠DAI积分(1.8±0.4)低于NS组(2.8±1.0),从第5天开始各治疗组DAI均明显降低.B组、L组、S组第8天时结肠长度分别为(9.0±0.6)、(9.3±0.6)、(8.8±1.1)cm,均大于NS组[(8.1±0.6)cm,P值均＜0.05].第8天时L组小鼠结肠黏膜病理组织学明显改善(组织学评分6.0±1.0).B组和L组IL-10和HSP70表达上调,TNF-α表达下调,GR无变化.结论 青春双歧杆菌BF0624和嗜酸乳杆菌LT0637均对溃疡性结肠炎有治疗作用,益生菌的治疗机制可能与上调HSP70和IL-10以及下调TNF-α的表达有关.     

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。     

姜黄素对DSS诱导的小鼠溃疡性结肠炎的疗效

目的:观察姜黄素对葡聚糖硫酸钠(DSS)诱导的小鼠溃疡性结肠炎的疗效,并探讨其作用机制.方法:选♀BALB/c小鼠60只,随机分为4组,每组15只.A组:正常对照组:B组:DSS结肠炎组,小鼠每日自由摄取5%DSS溶液:C组:姜黄素治疗组,小鼠自由摄取5%DSS溶液,每日腹腔注射姜黄素悬液30 mg/kg;D组:地塞米...     

趋化因子SLC在小鼠实验性结肠炎中的表达和意义

背景：次级淋巴组织趋化因子（SLC）是一种CC型趋化因子,主要功能为趋化各种淋巴细胞向外周淋巴组织或器官归巢。既往研究发现结肠组织SLC表达增高可能参与了溃疡性结肠炎（UC）的发病。目的：明确SLC在UC中的作用及其作为UC治疗靶点的可能性。方法：24只雌性BALB/c小鼠随机分为对照组、DSS模型组和地塞米松（DXM）治疗组,后两组饮用5% DSS溶液7 d诱导实验性结肠炎以模拟人类UC,DXM治疗组于造模第3 d起腹腔注射DXM 0.4 mg/kg qd×5 d。实验过程中评估疾病活动指数（DAI）。第8 d处死各组小鼠,行结肠大体形态和组织学评分,以免疫组化染色和RT-PCR检测结肠组织SLC表达。结果：对照组结肠组织SLC表达微弱,DSS模型组SLC mRNA和蛋白表达均较对照组显著上调（P〈0.01）,DXM治疗组SLC表达较DSS模型组显著降低（P〈0.01）,伴DAI以及结肠大体形态和组织学评分改善（P〈0.01）。结论：结肠组织SLC表达增高与UC发病有关,针对SLC的靶向治疗可作为UC的治疗选择。     

丝裂原活化蛋白激酶选择性抑制剂对葡聚糖硫酸钠结肠炎的影响

目的探讨p38丝裂原活化蛋白激酶（p38MAPK）选择性抑制剂SB203580对葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的影响。方法24只雌性BALB／C小鼠均分为三组：正常对照组、DSS结肠炎组和SB203580干预组。结肠炎组小鼠每日自由摄取5％DSS溶液．干预组小鼠在摄取5％DSS溶液72h后，每日腹腔注射SB2035801mg／kg体质量。各组小鼠每日记录疾病活动指数（DAI）评分，H-E染色观察小鼠结肠黏膜组织学改变。ELISA法测定结肠组织巾肿瘤坏死因子（TNF）-a含量。免疫组化染色观察磷酸化的活化转录因子2（P-ATF2）在结肠组织炎性细胞内的表达情况。结果正常对照组和DSS结肠炎组小鼠的DAI评分为0．224-0．09和4．81±1．08（P〈0．05），组织学评分为1．03±0．38和11．0±0．75（P〈0．05），经SB203580干预后分别为1．96±0．89和7．16±1．46，与结肠炎组小鼠比较差异有统计学意义（P00．05）。正常对照组与DSS结肠炎组小鼠的结肠匀浆TNF-a含量分别为（42．98±17．31）和（128．34±33．76）pg／ml（P〈0．05），SB203580于预后下降为（81．86±25．11）pg／ml，与结肠炎组小鼠比较差异有统计学意义（P〈0．05）。正常对照组与结肠炎组小鼠结肠组织炎性细胞P-ATF2的表达分别为（6．91±1．83）％和（81．02±12．35）％（P〈0．05），经SB203580处理后为（38．59±8．12）％，与结肠炎组小鼠比较差异有统计学意义（P00．05）。结论阻断p38MAPK信号转导通路可明显缓解DSS诱导的结肠炎。预示此信号转导通路可为溃疡性结肠炎新药研究提供有价值的靶标。     

复方甘草酸苷对小鼠实验性结肠炎NF-κB、STAT3信号转导通路的影响

背景：溃疡性结肠炎（UC）的病因、发病机制不明,且缺乏有效治愈手段.对相关信号转导通路的研究有助于了解药物干预的作用机制.目的：观察复方甘草酸苷对小鼠实验性结肠炎的治疗作用及其对NF-κB、STAT3信号转导通路的影响.方法：40只健康昆明小鼠随机分为四组,一组为正常对照组,另三组以噁唑酮诱导实验性结肠炎,随后分别腹腔注射0.9%NaCl溶液（模型对照组）、复方甘草酸苷（甘草酸苷组）或予柳氮磺砒啶（SASP）灌胃（SASP组）7 d.观察各组小鼠疾病活动指数（DAI）、结肠组织大体和组织学损伤评分以及髓过氧化物酶（MP0）活性,蛋白质印记法检测结肠黏膜NF-κB、STAT3活化水平.结果：模型对照组DAI、大体和组织学损伤评分、MP0活性以及结肠黏膜固有层单个核细胞中活化NF-κB p65、STAT3的表达均显著高于正常对照组（P＜0.05）,甘草酸苷组和SASP组则较模型对照组显著降低（P＜0.05）,甘草酸苷组与SASP组间仅DAI和组织学损伤评分有显著差异（P＜0.05）.结论：复方甘草酸苷能有效改善小鼠实验性结肠炎的炎症活动水平,其作用机制可能与下调NF-κB、STAT3信号转导通路有关.     

The Microvacular Thrombi of Colonic Tissue in Ulcerative Colitis

Mucosal microvacular thrombi in rectal biopsies were observed in some ulcerative colitis (UC). Heparin may be effective in steroid resistant UC in some studies, however, the new results of meta-analysis demonstrated a non-significant effect of heparin in controlled clinical trials, differing markedly from observational studies. The objective of this study was to identify colonic microvascular thrombi in larger cases with UC, and analyse its possible risk factors: age, gender, histologic score, extent of lesions and operation or biopsy specimens, and assess the significance of microvascular thrombosis in patients with UC. The microvascular thrombi were identified by immunohistochemical staining with anti-CD61 monoclonal antibody and Martius scarlet blue (MSB) staining in 40 colonic tissue samples of UC (31 biopsy specimens and nine operated cases) and 12 cases of normal colon tissue from operated colonic carcinoma. Logistic regression analysis was used to assess the relationship of age, gender, degree of histology, origin of the specimens, extent of lesions and microvascular thrombi examined. Microvascular thrombi were positive in 14 of 40 UC cases, and none in the controls. The presence of microvascular thrombi was related to operation specimens with odds ratio 11.667, P=0.0179, it might be also related to histologic score (OR=1.350) and extent of lesions (OR=1.619). These results suggest that microvascular thrombosis may be one of the important pathogenesis in some UC, and that the effect of anticoagulant treatment still needs to be assessed.     

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。     

白花丹参对自发性高血压大鼠心肌病变的影响

目的观察长期应用白花丹参水提物对自发性高血压大鼠心肌病变的影响及其机制。方法24只12周龄SHR大鼠随机分为3组：SHR组、白花丹参高剂量组（SMH）和白花丹参低剂量组（SML）。以WKY大鼠为阴性对照。灌胃给药12周后,记录24h清醒动脉血压、左心室重量指数（LVMI）,测血浆中一氧化氮合酶（cNOS）、一氧化氮（NO）、内皮素（ET）,左心室组织切片用HE和VanGieson染色,全自动图像分析系统进行分析．结果与WKY大鼠相比较,SHR组的血压、LVMI、心肌细胞直径（TDM）、心肌细胞面积（CA）、心肌组织胶原体积比例（CVF）和心肌血管周围胶原面积与管腔面积的比例（PVCA）显著升高[（190±19）／（143±11）mmHg、（4．71±0．54）mg／g、（32．35±5．87）μm、（560．53±90．62）μm^2,（8．13±0．71）％和（6．01±0．22）％],血浆ET水平显著升高,cNOS、NO、超氧化物歧化酶（SOD）均显著降低[（289．39±26．38）ng／ml、（54．41±6．25）μmol／L、（5．509±0．054）U／ml、（90．05±10．27）U／m1]。而白花丹参组,除收缩压外,各指标与SHR组比较差异均有统计学意义（P〈0．05）。结论白花丹参具有抑制自发性高血压大鼠心肌病变的作用。其机制可能与改善ET—NO系统和改善内皮功能障碍有关。     

Evaluation of the effect of pyrrolidine dithiocarbamate in suppressing inflammation in mice with dextran sodium sulfate-induced colitis

AIM: To evaluate the effect of pyrrolidine dithio- carbamate (PDTC; an NF-κB inhibitor) administered at low (50 mg/kg) and high (100 mg/kg) doses in suppressing colitis in mice with dextran sodium sulfate (DSS)-induced colitis. METHODS: Mice were divided into a DSS-untreated group (normal group), DSS-treated control group, DSS+PDTC-treated groupⅠ(low-dose group), and DSS+PDTC-treated groupⅡ (high-dose group). In each group, the disease activity index score (DAI score), intestinal length, histological score, and the levels of activated NF-κB and inflammatory cytokines (IL-1β and TNF-α) in tissue were measured. RESULTS: The DSS+PDTC-treated groupⅡ exhibited suppression of shortening of intestinal length and reduction of DAI score. Activated NF-κB level and IL-1β and TNF-α levels were significantly lower in DSS+PDTC- treated groupⅡ. CONCLUSION: These findings suggest that PDTC is useful for the treatment of ulcerative colitis.     

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.     

川芎嗪对实验性溃疡性结肠炎治疗作用的研究

目的：研究川芎嗪对小鼠溃疡性的炎的治疗作用及其机制。方法：在小鼠溃疡性结肠炎模型上观察川芎嗪的治疗作用,并用免疫组化LSAB（labelled streptavidin biotin)法检测肠组织中P选择素的表达,用ELISA法检测血浆P选择素含量。结果：溃疡性结肠炎小鼠结肠粘膜充血、水肿、糜烂或溃疡性形成;粘膜炎症细胞浸润（主要为中性粒细胞）及隐窝脓肿形成;川芎嗪治疗组小鼠未见明显病理变化,疾病活动指数（DAI）和病理学评分明显改善。免疫组化和ELISA检测发现,溃疡性结肠炎时肠组织P选择素表达和血中P选择素水平显著升高,经川芎嗪治疗的小鼠P选择素明显下降。结论：P选择素与溃疡性结肠炎密切相关,川芎嗪对溃疡性结肠炎具有治疗作用。     

The vagus nerve: a tonic inhibitory influence associated with inflammatory bowel disease in a murine model

BACKGROUND & AIMS: The recently proposed Inflammatory Reflex describes an interaction between the vagus nerve and peripheral macrophages, resulting in attenuation of proinflammatory cytokine release in response to systemic exposure to bacterial endotoxin. The purpose of this study was to determine whether a similar vagus/macrophage axis modulates the inflammatory responses in the colon in mice. METHODS: We assessed the Disease Activity Index (DAI), macroscopic and histologic damage, serum amyloid-P level, and myeloperoxidase activity in colitis induced by administration of dextran sodium sulfate (DSS) in healthy and vagotomized C57BL/6 and in mice deficient in macrophage-colony stimulating factor (M-CSF)-induced and in hapten-induced colitis. A pyloroplasty was performed in vagotomized mice. RESULTS: DAI, macroscopic and histologic scores, myeloperoxidase activity, levels of serum amyloid-P, and colonic tissue levels of interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha were increased significantly in vagotomized mice 5 days post-DSS and 3 days after hapten-induced colitis compared with sham-operated mice that received DSS or the hapten. Pretreatment with nicotine significantly decreased each of these markers in vagotomized mice with DSS colitis, and all markers except DAI and IL-6 in sham-operated DSS-treated mice. Conversely, hexamethonium treatment significantly increased each of these markers in the sham-operated DSS-treated mice. Vagotomy had no effect on the colitis in M-CSF-deficient mice. CONCLUSIONS: The vagus nerve plays a counterinflammatory role in acute colitis via a macrophage-dependent mechanism, involving hexamethonium-sensitive nicotinic receptors. The identification of a counterinflammatory neural pathway would open new therapeutic avenues for treating acute exacerbations of inflammatory bowel disease.