Glutathione supplementation improves oxidative damage in experimental colitis

BACKGROUND: The pathogenesis of inflammatory bowel disease is due, in part, to enhanced free-radical production and reduced antioxidant potential in mucosa cells. AIM: We evaluated in a rat model of trinitrobenzensulphonic acid (TNBS) colitis to see whether parenteral administration of glutathione is able to improve mucosal oxidative damage at onset (study A) and during chronic phases of colitis (study B). METHODS: In study A, the rats were injected with a single dose of glutathione (200 mg/kg, i.p.) or saline (0,2 ml, i.p.) 1 h before colitis induction and killed 1 h later. In study B, rats with induced colitis were treated with daily injection of glutathione (50 mg/kg, i.p.) or saline (0,2 ml, i.p.), and killed at 1, 2, 4 and 8 weeks. We evaluated on mucosal samples the macroscopic and histological damage and the oxidative stress assessed by the mucosal levels of lipoperoxides, malonyldialdehyde, glutathione and cysteine. RESULTS: In study A, colitis induction caused a significant increase to the total histological score (p<0.05), lipoperoxide and malonyldialdehyde levels (p<0.001), but did not affect glutathione and cysteine content. Glutathione pre-treatment decreased both total histological score (p<0.05) and lipoperoxide and malonyldialdehyde values (p<0.001). In study B, the extensive macroscopic and histological colonic damage induced by TNBS was accompanied by a reduction of glutathione and cysteine mucosal levels (p<0.01) and increased lipid peroxidation. Glutathione supplementation significantly improved colonic damage (p<0.01), restored glutathione and cysteine levels, and decreased, and even, if not totally, abolished lipid peroxidation (p<0.001). CONCLUSION: This paper further supports the pathogenic role of the imbalance in oxidant/antioxidant content in inducing mucosal colonic damage.     

铁沉积对大鼠肝纤维化影响的机制研究

目的探讨铁沉积对大鼠肝纤维化影响的机制。方法随机将39只SD大鼠分为模型组和空白对照组,采用二甲基亚硝胺(DMN,10μL·kg-1)腹腔注射,制作大鼠肝纤维化模型。造模大鼠在注射DMN 1 w后,再将模型大鼠随机分为模型组(15只)和去铁铵组(12只)。两组大鼠分别自第3 w开始腹腔注射生理盐水或100 mg·kg-1去铁铵,3次/w,2 w后处死动物。取肝组织分别行HE染色、Masson染色、普鲁士蓝染色;采用免疫组化法检测肝组织α-平滑肌肌动蛋白(α-SMA)的表达;采用火焰原子吸收光谱法(FAAS)测定大鼠肝组织铁浓度(HIC);采用ELISA法检测大鼠血清铁蛋白、转铁蛋白;使用全自动生化分析仪检测肝功能、血清铁水平;采用PCR法检测肝组织转化生长因子(TGF)-β1 m RNA水平。结果肝组织病理学检查显示,伴随着胶原纤维的沉积、肝细胞变性坏死和肝星状细胞(HSC)大量活化,模型组大鼠铁负载显著增加;铁沿纤维间隔分布,主要沉积于库普弗细胞(KC)和HSC;模型组肝组织铁浓度为(0.778±0.098)mg/g,空白对照组为(0.436±0.043)mg/g,两组差别有统计学意义(LSD-t=5.15,P0.01);去铁铵组为(0.595±0.146)mg/g,显著低于模型组(LSD-t=-2.76,P0.05);模型组血清铁蛋白和转铁蛋白分别为(47.657±27.851)ng/m L和(0.322±0.099)mg/m L,空白对照组分别为(24.166±27.626)ng/m L和(0.653±0.170)mg/m L,去铁铵组分别为(10.261±12.466)ng/m L和(0.584±0.180)mg/m L,说明模型组铁蛋白明显增加,血清转铁蛋白明显减少,与空白对照组比较,差异均有统计学意义(LSD-t=2.21和-4.78,P0.05和P0.01);去铁铵能明显降低血清铁蛋白水平,增加血清转铁蛋白水平,与模型组比较差异有统计学意义(LSD-t=-3.52和3.77,P0.05和P=0.01);模型组肝组织TGF-β1m RNA水平为(11.896±0.63),空白对照组为(2.292±0.222),两组差别有统计学意义(LSD-t=25.95,P0.01),去铁铵组为(7.481±0.745),显著低于模型组(LSD-t=-11.95,P0.01)。结论铁沉积对肝纤维化的发生发展起到重要作用,其机制可能与铁沉积于KC和HSC并促进HSC活化有关。     

双歧杆菌抑制小鼠实验性结肠炎肠道炎症反应的研究

目的观察补充益生菌对葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎的影响,探讨益生菌对结肠炎的治疗作用和可能机制。方法将小鼠分为4组:正常对照组、DSS组、柳氮磺胺吡啶(SASP)组和双歧杆菌组。建立小鼠急性DSS结肠炎模型。SASP组在饮DSS水同时予SASP灌胃。双歧杆菌组在实验开始前7d予双歧杆菌灌胃至实验结束。每天观察各组疾病活动指数(DAI),并在实验结束后检测各组小鼠炎症肠段肿瘤坏死因子(TNF)α、核因子(NF)κBP65、髓过氧化物酶(MPO)等的表达。结果自实验第4天开始,SASP组和双歧杆菌组DAI明显低于DSS组。实验结束时,SASP组和双歧杆菌组炎症肠段TNFα[(10.01±1.11)和(10.45±0.98)pg·mg-1·ml-1]、MPO[(3.21±0.20)和(3.24±0.16)U/g组织]等的水平较DSS组[(13.35±1.01)pg·mg-1·ml-1和(3.63±0.23)U/g组织]均明显降低,NFκBP65阳性的炎症细胞数减少。结论给小鼠预服双歧杆菌能有效抑制炎症肠段炎症细胞NFκB的活化及炎性细胞因子的分泌,减轻肠道炎症反应。     

缺锌对衰老小鼠抗氧化系统和肝脏DNA损伤修复功能的影响

目的　通过D 半乳糖诱导小鼠衰老模型 ,探讨缺锌对衰老小鼠抗氧化系统和肝脏DNA损伤与修复的影响。　方法　雄性 3月龄小鼠 70只 ,随机分成 5组 :青年组、衰老模型组、衰老缺锌组、衰老配喂组和衰老补锌组。各衰老组按 10 0mg /kg经颈背部皮下给予D 半乳糖注射液 ,青年组给予等剂量的生理盐水 ,连续 30d。衰老缺锌组和补锌组喂饲缺锌饲料 (含锌 1 6 1μg/kg) ,其他组喂饲正常锌饲料 (含锌 5 0 μg/kg) ,最后 2周补锌组喂饲补锌饲料 (10 0 μg/kg)。第 30天处死小鼠 ,取样检测血清锌、肝锌、超氧化物歧化酶、丙二醇、肝脂褐质和DNA损伤情况。　结果　与衰老模型组相比 ,衰老缺锌组血清锌 (0 5 3± 0 1)mg/L、肝锌 (14 5 4± 2 18)mg/L水平下降 ,血清和肝超氧化物歧化酶活性〔(14 2 87± 10 16 )NU/ml和 (180 11± 13 2 2 )NU/ml,P <0 0 5〕降低 ,丙二醇含量升高 ,肝脂褐质含量增高 ;彗星试验显示衰老缺锌组小鼠肝DNA损伤加重 ,彗星细胞尾长 /总长比值显著增加。补锌后上述指标均有改善。　结论　锌可有效的影响衰老的速度和程度 ,缺锌可加速衰老的进程 ,适当补锌有助于延缓衰老。     

Therapeutic effects of four strains of probiotics on experimental colitis in mice

AIM： To investigate the therapeutic effects of four strains of probiotics （E. feacalis, L. acidophilus, C. butyricum and B. adolescentis） on dextran sulphate sodium （DSS）-induced experimental colitis in Balb/c mice. METHODS： Eighty Balb/c mice were randomly divided into 8 groups. Weight-loss, fecal character, fecal occult blood and hematochezia were recorded daily. Disease activity index （DAI） scores were also evaluated everyday. Length of colon was measured and histological scores were evaluated on the 13th day. Myeloperoxidase （MPO） activity was detected. Interleukin-1 （IL-1） and IL-4 expression was detected by ELISA and RT-PCR. RESULTS： The four strains of probiotics relieved the inflammatory condition of DSS-induced experimental colitis in mice. Weight loss was slowed down in all probiotics-treated mice. Even weight gain was observed by the end of probiotics treatment. The DAI and histological scores of probiotics-treated mice were lower than those of mice in the control group （1.9 ± 0.2 vs 8.6 ± 0.4, P 〈 0.05 for E. faecalis）. The length of colon of probiotics-treated mice was longer than that of mice in the control group （10.3 ± 0.34 vs 8.65 ± 0.77, P 〈 0.05 for E. faecalis）. The four strains of probiotics decreased the MP activity and the IL-1 expression, but increased the IL-4 expression. E. faecalis had a better effect on DSS-induced experimental colitis in mice than the other three strains. CONCLUSION： The four strains of probiotics have beneficial effects on experimental colitis in mice, E. faecalis has a better effect on DSS-induced experimental colitis in mice than the other three strains. Supplement of probiotics provides a new therapy for UC.     

NO、NOS在大鼠实验性结肠炎中的动态变化及意义

目的　观察大鼠实验性结肠炎发生发展过程中一氧化氮 (nitricoxide ,NO)、一氧化氮合酶 (nitricoxidesynthase ,NOS)的动态变化 ,了解NO、NOS同大鼠实验性结肠炎的关系。方法　采用 2 ,4 二硝基氯苯 (2 ,4 dinitrochlorobenzene ,DNCB)诱发大鼠实验性结肠炎模型 ;Wistar雄性大鼠 70只 ,检测造模前 (Ⅰ组 ) ,造模后第 1天 (Ⅱ组 )、第 1周 (Ⅲ组 )、第 2周 (Ⅳ组 )、第 4周 (Ⅴ组 )结肠粘膜NO、NOS的动态变化 ,同时观察其病理改变 ;结果用 x±s表示 ,采用单因素方差分析对数据进行统计学处理 ,以P <0 .0 5作为差异有显著性的检验水准。结果　 1、Ⅱ、Ⅲ、Ⅳ组同Ⅰ、Ⅴ组相比 ,结肠粘膜NOS的活性及NO的水平明显升高 ,经统计学分析差异显著(P <0 .0 1) ,而Ⅰ、Ⅴ组间上述指标差异无显著性 (P >0 .0 5 )。 2、病理学改变 :Ⅰ组未见明显病理学变化 ;Ⅱ、Ⅲ、Ⅳ组粘膜及粘膜下层明显充血、水肿 ,炎性细胞浸润 ,腺体杯状细胞减少 ,有糜烂及溃疡形成 ;Ⅴ组溃疡基本愈合 ,残存溃疡有明显修复性改变 ,如粘膜上皮修复、肉芽组织增生、瘢痕形成等。结论　NOS、NO过量生成和大鼠实验性结肠炎有关。     

益生菌治疗大鼠实验性结肠炎效果观察及对T细胞亚群的影响

目的评价益生菌对大鼠实验性结肠炎的疗效,以及研究治疗后体内T细胞亚群变化情况。方法选择北京大学人民医院消化内科与北京医院特需医疗科于2004年9月至2005年2月建立实验性结肠炎模型,设立不同剂量益生菌治疗组、阴性对照组和阳性对照治疗组(泼尼松治疗组及柳氮磺胺吡啶治疗组),组织学积分评定疗效;流式细胞仪检测外周血、脾脏和结肠CD4 、CD8 T细胞亚群变化情况。结果大剂量益生菌对治疗大鼠实验性结肠炎有效;结肠炎大鼠结肠内CD4 、CD8 T细胞均增加,益生菌治疗后回落,而CD4 /CD8 比值及外周循环T细胞亚群无变化。结论大剂量益生菌治疗大鼠实验性结肠炎有效,可能与免疫调节机制有关。     

Favorable response to subcutaneous administration of infliximab in rats with experimental colitis

AIM: To investigate the influence of infliximab (Remicade) on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic acid (TNBS) in rats. METHODS: Thirty-six Wistar rats were allocated into four groups (three groups of six animals each and a fourth of 12 animals). Six more healthy animals served as normal controls (Group 5). Group 1: colitis was induced by intracolonic installation of 25 mg of TNBS dissolved in 0.25 mL of 50% ethanol and infliximab was subcutaneously administered at a dose of 5 mg/kg BW; Group 2: colitis was induced and infliximab was subcutaneously administered at a dose of 10 mg/kg BW; Group 3: colitis was induced and infliximab was subcutaneously administered at a dose of 15 mg/kg BW; Group 4: colitis was induced without treatment with infliximab. Infliximab was administered on d 2-6. On the 7~(th) d, all animals were killed. The colon was fixed in 10% buffered formalin and examined by light microscopy for the presence and activity of colitis and the extent of tissue damage. Tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) were also measured. RESULTS: Significant differences concerning the presence of reparable lesions and the extent of bowel mucosa without active inflammation in all groups of animals treated with infliximab compared with controls were found. Significant reduction of the tissue levels of TNF-α in all groups of treated animals as compared with the untreated ones was found (0.47±0.44, 1.09±0.86, 0.43±0.31 vs 18.73±10.53 respectively). Significant reduction in the tissue levels of MDA was noticed in group 1 as compared to group 4, as well as between groups 2 and 4. CONCLUSION: Subcutaneous administration of infliximab reduces the inflammatory activity as well as tissue TNF-α and MDA levels in chemical colitis in rats. Infliximab at a dose of 5 mg/kg BW achieves better histological results and produces higher reduction of the levels of TNF-α than at a dose of 10 mg/kg BW. Infliximab at a dose of 5 mg/kg BW produces higher reduction of tissue MDA levels than at a dose of 15 mg/ kg BW.     

氟中毒对大鼠口腔粘膜细胞和肝细胞DNA损伤的影响

目的：研究氟中毒对大鼠口腔粘膜细胞和肝细胞DNA损伤的影响。方法：雄性SD大鼠饮用含150mg/L氟化钠(NaF)的蒸馏水溶液4周，用单细胞凝胶电泳检测细胞DNA损伤。结果：氟中毒能明显诱导大鼠口腔粘膜细胞和肝细胞DNA损伤，总损伤细胞百分率分别为50．20％和44．80％。结论：氟中毒能引起大鼠口腔粘膜细胞和肝细胞DNA损伤。     

DNA content and mucosal dysplasia in ulcerative colitis

In an unselected population of 108 patients with ulcerative colitis in an ongoing endoscopic cancer surveillance program, high-grade dysplasia was diagnosed in 3, low-grade dysplasia in 11, and mucosal changes indefinite for dysplasia in 11 patients. The abnormal biopsy specimens from these 25 patients and samples from other parts of the large bowel obtained at the same examination were investigated by flow cytometric DNA analysis. One hundred thirty-six of 160 samples (85 percent) gave evaluable DNA histograms and, accordingly, 23 patients were retrospectively investigated. Six patients (26 percent) showed aneuploidy (abnormal DNA stemlines) and 1 had possible aneuploidy. All 3 patients with high-grade dysplasia showed aneuploidy (or possible aneuploidy) preceding or coexisting with the severe dysplastic changes. In 1 of these patients, the presence of aneuploidy preceded two diploid carcinomas. One patient was found to have had aneuploidy for seven years without evident malignant transformation. Further prospective studies are necessary to determine the value of DNA analysis in relation to morphologic examination in surveillance of patients with ulcerative colitis.     

嗜酸乳杆菌胞壁粗提物及DNA对溃疡性结肠炎小鼠模型的作用

目的:观察嗜酸乳杆菌BCW和DNA对实验性结肠炎的治疗作用.方法:40只♀BABL/c小鼠随机分为正常组、嗜酸乳杆菌BCW组、嗜酸乳杆菌DNA组和生理盐水组,除正常组小鼠外,其余各组自由饮用1.5%DSS 7 d建立小鼠结肠炎模型,从实验第1天开始,给予嗜酸乳杆菌BCW(20μg/10g)、嗜酸乳杆菌DNA(0.2 μ...     

Juvenile ferric iron prevents microbiota dysbiosis and colitis in adult rodents

AIM: To assess whether juvenile chronic ferric iron ingestion limit colitis and dysbiosis at adulthood in rats and mice.METHODS: Two sets of experiments were designed. In the first set, recently weaned mice were either orally administered ferrous (Fe²⁺) iron salt or ferric (Fe³⁺) microencapsulated iron for 6 wk. The last week of experiments trinitrobenzene sulfonic acid (TNBS) colitis was induced. In the second set, juvenile rats received the microencapsulated ferric iron for 6 wk and were also submitted to TNBS colitis during the last week of experiments. In both sets of experiments, animals were sacrificed 7 d after TNBS instillation. Severity of the inflammation was assessed by scoring macroscopic lesions and quantifying colonic myeloperoxidase (MPO) activity. Alteration of the microflora profile was estimated using quantitative polymerase chain reaction (qPCR) by measuring the evolution of total caecal microflora, Bacteroidetes, Firmicutes and enterobacteria.RESULTS: Neither ferrous nor ferric iron daily exposures at the juvenile period result in any effect in control animals at adulthood although ferrous iron repeated administration in infancy limited weight gain. Ferrous iron was unable to limit the experimental colitis (1.71 ± 0.27 MPO U/mg protein vs 2.47 ± 0.22 MPO U/mg protein in colitic mice). In contrast, ferric iron significantly prevented the increase of MPO activity (1.64 ± 0.14 MPO U/mg protein) in TNBS-induced colitis. Moreover, this positive effect was observed at both the doses of ferric iron used (75 and 150 mg/kg per day po - 6 wk). In the study we also compared, in both rats and mice, the consequences of chronic repeated low level exposure to ferric iron (75 mg/kg per day po - 6 wk) on TNBS-induced colitis and its related dysbiosis. We confirmed that ferric iron limited the TNBS-induced increase of MPO activity in both the rodent species. Furthermore, we assessed the ferric iron incidence on TNBS-induced intestinal microbiota dysbiosis. At first, we needed to optimize the isolation and quantify DNA copy numbers using standard curves to perform by qPCR this interspecies comparison. Using this approach, we determined that total microflora was similar in control rats and mice and was mainly composed of Firmicutes and Bacteroidetes at a ratio of 10/1. Ferric juvenile administration did not modify the microflora profile in control animals. Total microflora numbers remained unchanged whichever experimental conditions studied. Following TNBS-induced colitis, the Firmicutes/Bacteroidetes ratio was altered resulting in a decrease of the Firmicutes numbers and an increase of the Bacteroidetes numbers typical of a gut inflammatory reaction. In parallel, the subdominant population, the enterobacteria was also increased. However, ferric iron supplementation for the juvenile period prevented the increase of Bacteroidetes and of enterobacteria numbers consecutive to the colitis in both the studied species at adulthood.CONCLUSION: Rats and mice juvenile chronic ferric iron ingestion prevents colitis and dysbiosis at adulthood as assessed by the first interspecies comparison.     

益生菌治疗大鼠实验性结肠炎效果观察及对T细胞亚群的影响

目的评价益生菌对大鼠实验性结肠炎的疗效，以及研究治疗后体内T细胞亚群变化情况。方法选择北京大学人民医院消化内科与北京医院特需医疗科于2004年9月至2005年2月建立实验性结肠炎模型，设立不同剂量益生菌治疗组、阴性对照组和阳性对照治疗组（泼尼松治疗组及柳氮磺胺吡啶治疗组）。组织学积分评定疗效；流式细胞仪检测外周血、脾脏和结肠CD4^＋、CD8^＋T细胞亚群变化情况。结果大剂量益生菌对治疗大鼠实验性结肠炎有效；结肠炎大鼠结肠内CD4^＋、CD8^＋T细胞均增加，益生菌治疗后回落，而CD4^＋／CD8^＋比值及外周循环T细胞亚群无变化。结论大剂量益生菌治疗大鼠实验性结肠炎有效，可能与免疫调节机制有关。     

睡眠剥夺对大鼠心肌损伤效应的研究

目的:评估睡眠剥夺(SD)后大鼠心肌组织损伤程度并探讨其机制。方法: 将60只实验大鼠随机分为6组,每组10只。采用改良的多平台SD法(MMPM)建立SD模型,观察SD对心肌组织中缺血修饰白蛋白（IMA）、高敏C反应蛋白（hs-CRP）、还原型谷胱甘肽(GSH)、丙二醛(MDA)、超氧化物酶(SOD)含量的影响。结果: 与笼养组（CC组）和大平台组（TC组）相比,SD后大鼠心肌组织中IMA、hs-CRP、GSH及MDA的含量明显升高(P<0.05),且随着SD时间的延长有明显上升的趋势;而SOD的活性随着SD时间的延长有降低的趋势。结论: SD可引起大鼠心肌发生明显的氧化应激和炎症反应,且随着氧化应激和炎症反应的加重,心肌发生进行性缺血缺氧损害。     

DNA损伤与肝癌发生

肝癌是最常见的恶性肿瘤之一,其发生是一个复杂的生物学过程,具体机制尚未完全阐明.研究表明,乙、丙型肝炎病毒感染,黄曲霉毒素污染,饮酒,电离辐射以及具有有遗传毒性的人体代谢产物等能够诱导肝癌的发生,他们大都直接作用于肝细胞的遗传物质,引起DNA的损伤,这是发生肝癌的重要分子基础.DNA损伤后引起细胞一系列的反应,包括损伤信号的传导,损伤修复,诱导细胞死亡.这些诱因也能作用于损伤修复系统中的某个环节,使DNA损伤不能修复或不能正确修复,细胞发生恶性转化.因此,损伤DNA的累积就成为肝癌发生的重要分子机制,对其深入研究将会为肝癌的治疗奠定基础.     

乙型肝炎肝损伤中铁代谢异常的研究

目的：探讨血清铁代谢对乙型肝炎损伤的影响,方法：对收治的103例乙型肝炎患者按临床分型,观察铁代谢血清指标血清铁蛋白,转铁蛋白,血清铁,总铁结合力与乙型肝炎损伤的关系,结果:血清铁蛋白,转铁蛋白,血清铁和总铁结合,乙型肝炎损伤相关,其中血清铁蛋白,血清铁随肝损伤加重增加,转铁蛋白,总铁结合力随损伤加重而减少,结论：铁负荷过重可能协助HBV加重肝损伤,因此检测铁代谢指标可以对乙型肝炎的治疗和预后作出评价。     

Blocking MAdCAM-1 in vivo reduces leukocyte extravasation and reverses chronic inflammation in experimental colitis

Background Leukocyte recruitment to sites of intestinal inflammation is a crucial multi-step process, leading ultimately to the accumulation of cells in the inflamed tissue. These interactions in the gut are critically dependent on the mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is expressed on endothelial cells within the mesenteric lymph nodes and the lamina propria of the intestine. Here, we investigate the pathophysiologic role of MAdCAM-1 in the intestinal microcirculation in vivo.Methods Using a standard mouse model, chronic colitis was established after four cycles of dextran sodium sulfate (DSS) application. MAdCAM-1 expression was investigated by immunohistochemistry and Western blotting, as well as real-time polymerase chain reaction (PCR). Intravital microscopy was used to study the role of MAdCAM-1 on leukocyte-endothelium interactions and leukocyte extravasation.Results Significant changes in MAdCAM-1 were observed in mice with chronic DSS-induced colitis. Upregulation of MAdCAM-1 expression in chronic colitis was demonstrated on a protein and messenger ribonucleic acid (mRNA) level. Anti-MAdCAM-1 treatment lead to a marked reduction (>60%) of leukocyte sticking and extravasation in vivo, compared to the controls. This was parallelled by a significant reduction (45%) of intestinal inflammation, as measured by the histologic grading score.Conclusion These in vivo results demonstrate a distinct role of MAdCAM-1 in inflammatory intestinal diseases, and suggest that therapeutic strategies targeting this adhesion molecule could be useful in the treatment of chronic colitis.S. Farkas and M. Hornung contributed equally to this work.     

硒和维生素C对氟致大鼠肝细胞DNA损伤的影响

目的研究氟对大鼠肝细胞DNA的损伤作用以及硒和维生素C对氟致大鼠肝细胞DNA损伤的影响。方法氟(F)组、氟 硒(F Se)组、氟 维生素C(F VC)组分别用NaF 150mg／L、NaF 150mg／L Na2SeO2 5mg／L、NaF 150mg／L VC 1000mg／L喂养雄性SD大鼠4周，应用单细胞凝胶电泳技术(SCGE)检测肝细胞DNA的损伤率。结果F组肝细胞DNA损伤率(44．80％)明显高于对照组(9．40％)；而F Se组(12．60％)和F VC组(14．60％)的DNA损伤率明显低于F组，与对照组差异无显著意义。结论过量氟摄入可导致大鼠肝细胞DNA损伤，而适量的硒和维生素C对氟致DNA损伤有一定的拮抗作用。     

化瘀通络汤对大鼠实验性溃疡性结肠炎血小板活化的影响

[目的]观察化瘀通络汤对大鼠实验性溃疡性结肠炎（UC）的疗效和对其血小板活化的影响，探讨化瘀通络汤治疗UC的机制及UC的发病机制。[方法]将动物按体重随机分为化瘀通络组、柳氮磺胺吡啶（SASP）组、模型对照组和正常对照组。其中除正常对照组外其余3组均采用2，4-二硝基氯苯和醋酸复合法制作UC大鼠模型。各组连续治疗4周后，取外周血测血清P-选择素和可溶性CD40配体（sCD40L）的水平。[结果]模型对照组血清P-选择素和sCD40L水平及肠黏膜损伤评分较正常对照组、化瘀通络组和SASP组显著升高（P〈0．05），而化瘀通络组与SASP组间差异无统计学意义（P〉0．05）。[结论]血小板活化在UC发病过程中起重要作用。化瘀通络汤治疗UC有效，其机制可能在于对血小板活化的阻抑而间接对免疫炎症进行调解，也可能直接通过对免疫炎症反应的调解而实现。     

选择性环氧合酶-2抑制剂塞来昔布在实验性结肠炎中的作用机制

目的　明确选择性环氧合酶 (COX) 2抑制剂—塞来昔布对 2 ,4 ,6 三硝基苯磺酸 (TNBS)诱导的大鼠结肠炎的作用 ,并初步探讨其作用机制。方法　将大鼠分为四组 :第 1组和第 2组为造模组 ,第 3组和第 4组为对照组。用 0 .2 5mlTNBS乙醇溶液 (TNBS浓度 2 5mg/ml,乙醇浓度 5 0 % )灌肠 ,诱导大鼠慢性实验性结肠炎模型。造模组大鼠于造模前 3h开始 ,分别给予塞来昔布 (1.2 5mg/kg ,第 1组 )和蒸馏水 (第 2组 ) ,每天 2次 ,共 7d。第 3组大鼠为正常对照组。第 4组大鼠以塞来昔布 (1.2 5mg/kg)灌胃 ,每天 2次 ,共 7d。于第 7天实验结束时处死所有存活动物 ,观察结肠黏膜的损伤程度 ,同时用放射免疫分析法测定结肠黏膜前列腺素E2 (PGE2 )水平。结果　造模组大鼠结肠损伤积分分别为11.15± 3.30 (第 1组 )和 8.5 0± 2 .82 (第 2组 ) ,均显著高于正常对照组 0 .6 2± 0 .0 9(P值均 <0 .0 1)。第 1组的结肠损伤积分显著高于第 2组 (P <0 .0 5 )。第 3组和第 4组的积分差异无显著性。造模组大鼠结肠黏膜PGE2浓度分别为 (12 .0 0± 4 .33)pg/ μg(第 1组 )和 (17.2 0± 9.6 2 ) pg/ μg(第 2组 ) ,均显著高于正常对照组的 (6 .0 2± 3.39) pg/ μg ,(P值均 <0 .0 5 )。第 1组的PGE2浓度显著低于第 2组 (P <0 .0 5 )