乌梅丸对溃疡性结肠炎大鼠结肠组织NF-kappaB p65的影响

目的: 比较乌梅丸与西药柳氮磺胺吡啶SASP组对溃疡性结肠炎大鼠结肠组织NF-kappaB p65疗效的大小, 并分析其作用机制. 方法: 应用2, 4-二硝基氯苯(DNCB)免疫加醋酸局部灌肠法建立UC大鼠模型, 将56只健康SD大鼠(雌雄各半), 按雌雄随机分4组, 分别为乌梅丸组、SASP组、模型组和正常组, 分别观察治疗后大鼠结肠黏膜组织匀浆NF-kappaB p65的变化. 结果: 在正常结肠组织中NF-kappaB p65无或仅有弱阳性表达, 模型组结肠黏膜组织NF-kappaB p65阳性细胞表达率明显高于正常组(45.67%±4.25% vs 10.45%±5.20%, P<0.05), 乌梅丸(26.32%±9.65%)和SASP(31.23%±5.18%)组阳性细胞率则明显低于模型组, 乌梅丸组阳性细胞率较SASP组更低. 结论: NF-kappaB与UC发病关系密切, 乌梅丸可能通过抑制NF-kappaB p65活性调节免疫功能达到治疗的目的.     

乌梅丸对溃疡性结肠炎大鼠结肠组织NF-κB p65的影响

目的:比较乌梅丸与西药柳氮磺胺吡啶SASP组对溃疡性结肠炎大鼠结肠组织NF-κB p65疗效的大小,并分析其作用机制.方法:应用2,4-二硝基氯苯(DNCB)免疫加醋酸局部灌肠法建立UC大鼠模型,将56只健康SD大鼠(雌雄各半),按雌雄随机分4组,分别为乌梅丸组、SASP组、模型组和正常组,分别观察治疗后大鼠结肠黏膜组织匀浆NF-κB p65的变化.结果:在正常结肠组织中NF-κB p65无或仅有弱阳性表达,模型组结肠黏膜组织NF-κB p65阳性细胞表达率明显高于正常组(45.67%±4.25% vs 10.45%±5.20%,P＜0.05),乌梅丸(26.32%±9.65%)和SASP(31.23%±5.18%)组阳性细胞率则明显低于模型组,乌梅丸组阳性细胞率较SASP组更低.结论:NF-κB与UC发病关系密切,乌梅丸可能通过抑制NF-κB p65活性调节免疫功能达到治疗的目的.     

奥曲肽对溃疡性结肠炎大鼠肠组织NF-κB p65的影响

目的探讨生长抑素（SST）类似物—奥曲肽对溃疡性结肠炎（UC）大鼠结肠组织核因子-κB（NF-κB）p65蛋白活性的影响及其机制。方法将雌性SD大鼠随机分为正常对照组、奥曲肽对照组、模型组、治疗组,每组各7只。模型组、治疗组大鼠用三硝基苯磺酸（TNBS）/乙醇溶液灌肠复制UC模型。评价各组实验大鼠大体及组织病理学改变,采用Western blot法检测结肠NF-κB p65蛋白的表达。结果奥曲肽可以显著改善结肠组织大体和组织学评分,降低NF-κB p65表达。结论NF-κB与UC发病关系密切,奥曲肽可能通过影响炎症反应的信号通路达到治疗目的。     

烟雾暴露对大鼠肺泡巨噬细胞核因子κB的影响及机制

核因子κB(NF-κB)是重要的转录调节因子，吸烟作为导致慢性阻塞性肺疾病(COPD)的重要因素．其对NF-κB的影响及作用机制尚不清楚。我们的实验通过在体及离体研究，探讨烟雾暴露对大鼠肺泡巨噬细胞(AM)、NF-κB的作用及相关机制。     

痛泻要方对溃疡性结肠炎模型大鼠结肠组织中NF-κBp65基因和蛋白表达的影响

目的探讨痛泻要方对溃疡性结肠炎(UC)模型大鼠结肠结肠组织中NF-κB p65蛋白和基因表达的疗效及作用机制。方法将实验动物分为6组,采用2,4,6-三硝基苯磺酸(TNBS)/乙醇灌肠法造模,肉眼观察结肠大体形态损伤并进行评分。以大鼠结肠组织中NF-κB p65为观察指标,采用RT-PCR和免疫组化法检测NF-κB p65蛋白和基因表达水平。结果肉眼观察模型组大鼠结肠组织黏膜层可见炎症和溃疡形成,与空白组比较P<0.05,证实模型成功。模型组大鼠结肠组织NF-κB p65基因和蛋白的表达量均高于空白组,差异有统计学意义(P<0.01);治疗后,痛泻要方高剂量组、中剂量组NF-κB p65基因和蛋白的表达量均较模型组降低(P<0.05、P<0.01)。结论痛泻要方对TNBS/乙醇法UC大鼠模型结肠黏膜NF-κB p65基因和蛋白的表达量有下调作用,提示痛泻要方治疗UC的作用机制之一可能是与NF-κB信号通路被激活有关。     

NF-κB在溃疡性结肠炎中的作用

NF-κB是一种多向转录调节因子,目前认为NF-κB参与溃疡性结肠炎的发病机制,并作为一种靶向因子在溃疡性结肠炎的治疗中开辟新的思路。此文对近年来相关方面的进展作一综述。     

普洱茶提取物对巨噬细胞株RAW264.7凋亡的作用

目的 通过观察普洱茶提取物对巨噬细胞株RAW264.7凋亡/迁移的作用以及可能的机制,探讨普洱茶改善动脉粥样硬化的可能机制。 方法 ①分组:普洱茶提取物处理细胞时间分组:0 h、12 h、24 h、36 h、48 h、60 h、72 h;普洱茶提取物浓度分组:0、1/64、1/128、1/256、1/512、1/1024;②TUNEL法检测巨噬细胞凋亡;③实时定量PCR、Western blot检测 P65、IκB-β表达水平;④Transwell实验观察细胞迁移能力。 结果 ①普洱茶提取物促进巨噬细胞的凋亡,且具有时间及浓度依赖性;②普洱茶提取物上调IκB-β mRNA及蛋白表达,且具有时间及浓度依赖性;普洱茶提取物下调P65 mRNA及蛋白表达,且具有时间及浓度依赖性;③普洱茶提取物抑制巨噬细胞迁移率,Bay11-7085（NF-κB活化抑制剂）同样抑制巨噬细胞迁移;Bay11-7085和普洱茶提取物同时与细胞共培养并不增加对细胞迁移能力的抑制。 结论 普洱茶提取物通过抑制NF-κB信号通路促进巨噬细胞凋亡并抑制其迁移,可能是其抗动脉粥样硬化的作用机制。     

雷公藤红素对三硝基苯磺酸诱导的大鼠结肠炎的保护作用

背景：传统药物对炎症性肠病疗效不甚理想，寻找新型而有效的药物一直是该领域的研究热点。目的：观察雷公藤红素对三硝基苯磺酸（TNBS）诱导的大鼠结肠炎的保护作用，并初步探讨其可能机制。方法：以TNBS诱导大鼠结肠炎模型。将动物随机分为正常对照组、模型组、助溶剂对照组以及雷公藤红素低剂量组（每天0．5mg／kg）和高剂量组（每天1mg／kg）。以大体和组织学评分评价结肠炎症程度。以免疫组化方法检测结肠组织核因子（NF）-kBp65的表达，以半定量逆转录聚合酶链反应（RT-PCR）检测白细胞介素（IL）-1β和肿瘤坏死因子（TNF）-α mRNA的表达。结果：高、低剂量雷公藤红素均能显著改善结肠组织大体和组织学评分，降低NF-kB p65以及IL-1β、TNF-α mRNA的表达。结论：雷公藤红素对TNBS诱导的大鼠结肠炎具有显著保护作用，抑制促炎细胞因子的产生可能是其主要作用机制之一。     

溃结汤对大鼠溃疡性结肠炎治疗及肠黏膜NF-κB的影响

目的探讨溃疡性结肠炎（UC）大鼠肠黏膜NF-κB的活化以及本科自拟中药溃结汤（KJT）对其影响和对UC的治疗作用。方法取50只健康成年Wistar大鼠,应用复合法（2,4-二硝基氯苯＋乙酸）制备细胞免疫反应性UC大鼠模型。取已造模成功Wistar大鼠40只,随机均分为模型组、KJT低剂量组、KJT高剂量组、柳氮磺胺吡啶（SASP）组,并设正常对照组Wistar大鼠10只。观察指标包括结肠重量,大体形态黏膜损伤程度评分,HE染色病理观察,扫描电镜肠黏膜损伤观察,NF-κB p65免疫组化染色（应用图像分析系统处理）。结果模型组结肠重量,大体形态黏膜损伤程度评分较对照组显著增加,NF-κB p65的表达水平显著升高,KJT低剂量组、KJT高剂量组、SASP组上述指标较模型组显著下降。结论 NF-κB表达的增加可能与UC的发生、发展有关;KJT和SASP的抗炎作用可能是通过抑制NF-κB的表达实现。     

Ameliorative effects of sodium ferulate on experimental colitis and their mechanisms in rats

AIM: To investigate the ameliorative effects of sodium ferulate (SF) on acetic acid-induced colitis and their mechanisms in rats.METHODS: The colitis model of Sprague-Dawley rats was induced by intracolon enema with 8 % (WV) of acetic acid.The experimental animals were randomly divided into model control, 5-aminosalicylic acid therapy group and three dose of SF therapy groups. The 5 groups were treated intracolonically and daily (8:00 am) for 7 days 24 h following the induction of colitis. A normal control group of rats clystered with normal saline instead of acetic acid was also included in the study.Pathological changes of the colonic mucosa were evaluated by the colon mucosa damage index (CMDI) and the histopathological score (HS). The insulted colonic mucosa was sampled for a variety of determinations at the end of experiment when the animals were sacrificed by decapitation.Colonic activities of myeloperoxidase (MPO) and superoxide dismutase (SOD), and levels of malondialdehyde (MDA)and nitric oxide (NO) were assayed with ultraviolet spectrophotometry. Colonic contents of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2)were determined by radioimmunoassay. The expressions of inducible nitric oxide synthase (iNOS), cyclo-oxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) p65 proteins in the colonic tissue were detected with immunohistochemistry.RESULTS: Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with acetic acid, which manifested as the significant increase of CMDI, HS, MPO activities, MDA and NO levels,PGE2 and TXB2 contents, as well as the expressions of iNOS,COX-2 and NF-κB p65 proteins in the colonic mucosa,although the colonic SOD activity was significantly decreased compared with the normal control (CMDI: 2.9±0.6 vs0.0±0.0;HS: 4.3±0.9 vs0.7±1.1; MPO: 98.1±26.9 vs24.8±11.5; MDA:57.53±12.36 vs9.21±3.85; NO: 0.331±0.092 vs0.176±0.045;PGE2: 186.2±96.2 vs 42.8±32.8; TXB2: 34.26±13.51 vs 8.83±3.75; iNOS: 0.365±0.026 vs0.053±0.015; COX-2:0.296±0.028 vs0.034±0.013; NF-κB p65:0.314±0.026 vs 0.039±0.012; SOD: 28.33±1.17 vs36.14±1.91; P<0.01).However, these parameters were found to be significantly ameliorated in rats treated locally with SF at the given dose (CMDI: 1.8±0.8, 1.6±0.9; HS: 3.3±0.9, 3.1±1.0; MPO:63.8±30.5, 36.2±14.2; MDA: 41.84±10.62, 37.34±8.58; NO:0.247±0.042; 0.216±0.033; PGE2: 77.2±26.9, 58.4±23.9;TXB2:18.07±14.83; 15.52±8.62; iNOS:0.175±0.018, 0.106±0.019;COX-2: 0.064±0.018, 0.056±0.014; NF-κBp65: 0.215±0.019,0.189±0.016; SOD: 32.15±4.26, 33.24±3.69; P<0.05-0.01).amelioration of colonic mucosal injury as evaluated by CMDI and HS.CONCLUSION: Administration of SF intracolonically may have significant therapeutic effects on the rat model of colitis induced by acetic acid enema, which was probably due to the mechanism of antioxidation, inhibition of arachidonic acid metabolism and NF-κB expression.     

阿魏酸钠对大鼠脑白质胶质纤维酸性蛋白表达的影响

目的探讨阿魏酸钠对大鼠前脑缺血再灌注（I/R）后白质胶质纤维酸性蛋白表达的影响。方法双侧颈总动脉夹闭法制备大鼠前脑I/R模型。雄性Wistar大鼠45只，随机分为假手术组（n=15），I/R组（n=15），I/R阿魏酸钠治疗组（n=15），每组按I/R2、4、6w3个时间点再分为3组（n=5）。模型制备免疫组化法检测I/R后2、4、6w胼胝体、内囊和脑室周围GFAP的表达。结果I/R后胼胝体、内囊和脑室周围GFAP的表达随时间延长逐渐增多，阿魏酸钠治疗组GFAP的表达较假手术组多，较缺血再灌注组减少，6w差异最显著（P〈0.05）。结论大鼠前脑缺血再灌注后白质GFAP表达增多，阿魏酸钠对脑白质缺血性损伤具有保护作用，其机制可能与调节星形胶质细胞活化状态，减轻内皮素对血管损伤有关。     

Polyethylene glycol enhances colonic barrier function and ameliorates experimental colitis in rats

Objective Polyethylene glycol (PEG) has been suggested to protect against pathogen colonization by improving colonic barrier function. We aimed to establish whether PEG 4000 affects colonic barrier function and the development of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. Materials and methods PEG was included in the drinking water for a period of 48 h before intracolonic administration of TNBS. Results and discussion PEG increased colonic surface hydrophobicity and diminished luminal bacterial load. Moreover, PEG markedly reduced mucosal damage and inflammation induced by TNBS. This protection effect appeared to be independent of its laxative properties since the laxatives mannitol or senna extracts had no effect on TNBS colitis. Using everted colonic sacs, pretreatment with PEG produced a lasting reduction in epithelial permeability to mannitol and dextran-70 K that correlated with decreased surface hydrophobicity. Conclusion Our results suggest that the protective effect of PEG on TNBS colitis is associated with reinforcement of the epithelial barrier. Sebastián Videla and Aurelia Lugea contributed equally to this study.     

阿魏酸钠对大鼠肾脏缺血再灌注损伤的作用

目的建立大鼠肾脏缺血再灌注损伤（IRI）模型，观察阿魏酸钠（SF）对大鼠肾脏是否具有保护作用，并初步探讨其机制。方法32只雄性Wistar大鼠，随机分为4组：①正常组，②假手术组，③模型组，④治疗组，测定各组血清肌酐（SCr）、尿素氮（BUN）及肾脏组织中丙二醛（MDA）和超氧化物歧化酶（SOD）水平，观察肾功能变化、组织过氧化情况及机体抗氧化能力；光镜下观察肾脏组织形态学变化。结果模型组各项指标与假手术组相比有显著差异，说明模型制作成功。同时治疗组可明显降低SCr、BUN及MDA含量，并升高SOD水平，与模型组相比有显著性差异，而且肾脏组织的病理改变减轻。结论SF对大鼠肾脏IRI有保护作用，其机制可能与对抗自由基、抗脂质过氧化等作用有关。     

Effects of the anti-ICAM-1 monoclonal antibody on dextran sodium sulphate-induced colitis in rats

Increased expression of intercellular adhesion molecule-1 (ICAM-1) in the colon of inflammatory bowel disease (IBD) has been reported. We evaluated the effects of monoclonal antibodies to ICAM-1 on acute colitis induced by dextran sodium sulphate (DSS) in rats. Colitis was induced by feeding rats 3% DSS for 7 days. Anti-ICAM-1 antibody or vehicle alone was injected intraperitoneally in rats daily from day 0 to day 6. On day 7 the rats were killed and colitis was evaluated histologically. Prophylactic treatment with anti-ICAM-1 significantly attenuated colonic damage, neutrophil infiltration and the shortening of the colon in DSS colitis. Our findings demonstrate that ICAM-1 plays an important role in this model of inflammatory bowel disease. Although this study does not directly address the effect of anti-ICAM-1 therapy in IBD, our findings encourage experiments using therapies that target ICAM-1 in rats with already developed disease.     

阿魏酸钠对特发性肺间质纤维化患者氧化应激及肺功能的影响

目的探讨阿魏酸钠对特发性肺间质纤维化（IPF）患者氧化应激及肺功能的影响。方法36例特发性肺间质纤维化住院患者被随机分为A、B两组,A组为阳性对照组,进行常规治疗,B组为治疗组,在常规治疗基础上给予阿魏酸钠,疗程12周。另选取20例健康体检者为正常对照组。测定IPF患者治疗前后及健康体检者肺总量（TLC）、一氧化碳弥散量（DLCO）以及血浆中丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH—Px）的含量。结果与正常对照组相比,IPF患者体内MDA显著升高,GSH—Px含量显著降低,TLC及DLCO也明显降低（P〈0．01）。应用阿魏酸钠后,B组患者上述指标的改善明显优于A组,差异具有显著性（P〈0．05）。结论氧化应激是引起IPF的原因之一,阿魏酸钠可能通过调节氧化应激水平,改善IPF患者的肺功能。     

Effects of anti-inflammatory therapy on bursting pressure of colonic anastomosis in murine dextran sulfate sodium induced colitis

Abstract

Background: In suspected Crohn’s disease (CD), non-diagnostic ileocolonoscopies are often followed by small bowel capsule endoscopy (SBCE). Adequate pre-selection of patients for SBCE is a key to optimize allocation of resources. We aimed to establish a rational approach for the CD diagnostic workflow, based on biochemical profile of patients with suspected CD, targeting an optimization of patients’ selection for SBCE.

Methods: Multicenter cohort study includes consecutive patients with suspected undergoing SBCE after non-diagnostic ileocolonoscopy. Minimum follow-up period after the capsule enteroscopy was six months. The outcome was confirmation of CD diagnosis. Univariate analysis and logistic regression were performed.

Results: In included 220 patients, 62.3% of women were with a mean age of 41?years [26–54]. A confirmed diagnosis of CD was established in 98 patients (44.5%). The initial univariate analysis identified variables above the threshold of marginal statistical association toward CD diagnosis (p?p?=?.128) and low serum Iron (OR 0.990 p?=?.025) as the independent variables with consistent correlation with CD diagnosis. Those two variables present a suitable discriminative power (AUC?=?0.669, p?Conclusion: In suspected CD, low serum iron and elevated CRP had a statistically significant association with CD diagnosis, being helpful to identify patients with higher CD probability before SBCE. However, the lack of a proper validation of the model leads us to currently recommend SBCE to all patients with suspected CD and negative ileocolonoscopy, as no specific biochemical profile can be used to confidently exclude small bowel CD.     

阿魏酸钠对糖尿病大鼠主动脉胶原非酶糖基化的影响

将链脲佐菌素诱发的糖尿病大鼠，以阿魏酸钠处理8周，可使糖尿病大鼠主动脉的胶原和胶原中糖基化终末产物的含量降低，其机制可能与阿魏酸钠保护抗氧化酶有关。     

Serum and tissue autoantibodies to colonic epithelium in ulcerative colitis

Sera and colonic tissue-bound immunoglobulin extracts from patients with ulcerative colitis and disease controls were examined immunohistochemically and by killer cell cytotoxicity assay for the presence of anticolonic epithelial autoantibodies. IgG yields in the tissue extracts from patients with colitis and control subjects were similar, and the extracts were uniformly autoantibody negative. Of 41 sera from patients with inflammatory bowel disease, 'classical' anticolon antibody was present in 41% and was commoner in patients with sclerosing cholangitis. Cytotoxic anticolon antibody was present in 20% overall and was strongly associated with disease activity; it did not correlate with the presence of 'classical' anticolon antibody. The heterogeneous and non-universal antiepithelial autoantibody response and the failure to detect tissue bound autoantibody in vivo argue against the hypothesis that humoral autoimmunity is of major importance in the pathogenesis of ulcerative colitis.