地榆对急性溃疡性结肠炎大鼠肠道菌群的影响

本实验旨在从肠道菌群角度探讨地榆对急性溃疡性结肠炎(UC)的保护作用及其初步机制。大鼠随机分为正常组、模型组及地榆低、高剂量组。采用3.5%葡聚糖硫酸钠(DSS)诱导急性UC模型,并予以灌胃给药。记录大鼠DAI疾病评分,HE染色观察组织形态变化,ELISA法检测炎症因子含量,高通量测序技术检测肠道菌群。结果显示,地榆可显著降低UC大鼠DAI疾病评分(P0.05),修复其结肠粘膜损伤,降低血清及结肠组织IL-6、IL-1β、TNF-α含量(P0.05);改善UC大鼠肠道菌群多样性,恢复菌群平衡。研究结果提示地榆可通过调节UC大鼠肠道菌群,修复结肠粘膜屏障,进而发挥治疗急性UC的作用。     

党参总皂苷对TNBS诱导的大鼠溃疡性结肠炎的保护作用及其机制

目的: 探讨党参总皂苷(TSC)对大鼠实验性溃疡性结肠炎(UC)的治疗作用及其作用机制。方法: 50只雄性Wistar大鼠随机分为5组:对照组、模型组、柳氮磺胺嘧啶(SASP)阳性对照组(0.3 g/kg)、TSC高剂量组(1.2 g/kg)、TSC低剂量组(0.4 g/kg),用三硝基苯磺酸(TNBS)/乙醇联合灌肠制作大鼠UC模型,给药21 d后,通过观察大鼠症状和体征、疾病活动指数(DAI)、结肠粘膜损伤指数(CMDI)、结肠组织形态;测定结肠组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、炎症因子白介素-6(IL-6)、白介素-10(IL-10)、肿瘤坏死因子α(TNF-α)的含量;检测结肠组织中细胞核内核转录因子-κB(NF-κB)蛋白表达;最终评价TSC的治疗效果。结果: 与对照组比较,模型组大鼠DAI、CMDI评分显著升高,结肠粘膜损伤严重,说明造模成功。与模型组比较,TSC高低剂量组均能显著降低UC大鼠DAI评分、CMDI评分(P＜0.05);改善结肠黏膜形态;升高结肠组织中SOD活力,降低MDA含量(P＜0.05),抑制结肠组织中IL-6、TNF-α mRNA水平,促进IL-10 mRNA表达(P＜0.01);同时降低结肠中NF-κB蛋白表达(P＜ 0.01),且TSC高剂量组优于低剂量组(P＜0.05)。结论: TSC对UC大鼠结肠黏膜损伤具有显著保护作用,以高剂量组为佳;其机制可能与抗脂质过氧化,抑制NF-κB信号通路从而调控炎性因子的释放有关。     

黄芪多糖对三硝基苯磺酸诱导溃疡性结肠炎大鼠的保护作用

本研究探讨黄芪多糖(APS)对2,4,6-三硝基苯磺酸(TNBS)诱导溃疡性结肠炎(UC)大鼠的保护作用。将72只SD大鼠随机分为正常组、模型组、柳氮磺胺吡啶(SASP)阳性组、APS低、中、高剂量组(100、200、400mg·kg-1),每组12只,除正常组外,每组以150mg·kg-1 TNBS乙醇溶液灌肠制备大鼠结肠炎模型。造模24h后,SASP阳性组及黄芪多糖组分别给予相应的药物进行灌胃干预,每日1次,连续给药14d。研究过程中观察大鼠体重、评价其活动指数(DAI)及结肠黏膜损伤(CMDI),并于给药结束后检测大鼠血清和组织中的炎症因子及生化指标。结果表明,黄芪多糖可以显著改善UC大鼠活动指数,减轻大鼠黏膜损伤,且APS高剂量组大鼠组织中丙二醛(MDA)、髓过氧化物酶(MPO)水平相比模型对照组显著降低,超氧化物歧化酶(SOD)水平显著增加(p<0.05);同时血清中炎症因子TNF-α、IL-6含量相比模型对照组显著降低,IL-10含量显著增加(p<0.05)。因此,黄芪多糖对TNBS诱导的大鼠溃疡性结肠炎具有一定的保护作用。     

IL-1、IL-6、TNF-α及IFN-γ在脾肾阳虚型溃疡性结肠炎模型大鼠血清及组织中的表达

目的通过对脾肾阳虚型溃疡性结肠炎(UC)模型大鼠血清及结肠组织中IL-1、IL-6、TNF-α及IFN-γ表达水平的检测,探讨它们在UC发生发展过程中的作用。方法采用灌服大黄水煎液+肌肉注射氢化可的松并结合TNBS(2,4,6-三硝基苯磺酸)+乙醇灌肠建立脾肾阳虚型UC动物模型。将60只大鼠随机分为空白组、脾肾阳虚型UC模型7、14d及21d组,采用酶联免疫法检测各组大鼠血清及结肠组织中IL-1、IL-6、TNF-α及IFN-γ的含量。结果与空白组比较,脾肾阳虚型UC模型组大鼠血清及结肠组织中IL-1、IL-6、TNF-α及IFN-γ含量明显升高(P0.05);尤以模型21d组最为明显。结论促炎性细胞因子IL-1、IL-6、TNF-α及IFN-γ在脾肾阳虚型UC发病过程中起重要作用。     

免疫致敏结合局部乙酸刺激法建立大鼠溃疡性结肠炎模型

目的结肠黏膜组织致敏法加乙酸局部刺激法建立复合大鼠溃疡性结肠炎模型。方法30只Wistar大鼠随机分为正常对照组、模型对照组、用药组(各10只),用结肠黏膜组织致敏法加乙酸局部刺激法建立大鼠复合溃疡性结肠炎模型后,用药组给予SASP灌胃,模型对照组和正常对照组给予生理盐水,均灌胃2周后处死大鼠,分离其结肠组织和血清。生化法检测各组结肠中MDA、SOD、GSH-PX、NO、TNOS和iNOS值,放免法测定大鼠血清及结肠IL-4及TNF-α含量变化,酶联免疫法测定大鼠血清IFN-γ含量变化。结果与空白对照组比较,模型组大鼠结肠组织MDA、NO、TNOS及iNOS含量升高,SOD、GSH-Px水平显著降低。与模型组比较,SASP组SOD、GSH-Px计数水平显著升高,组织MDA、NO、TNOS及iNOS含量降低。模型组血清和结肠IL-4含量较对照组明显降低,而模型大鼠血清和结肠TNF-α含量明显升高,模型组大鼠血清IFN-γ含量明显升高。SASP组IL-4含量升高,TNF-α和IFN-γ含量明显降低。结论改进的复合造模方法,可以较好的模拟人类UC病变的慢性活动性特点,适合药效观察和评价。     

谷氨酰胺对溃疡性结肠炎小鼠结肠损伤的影响

目的：探讨谷氨酰胺（Gln）对溃疡性结肠炎小鼠结肠黏膜损伤的影响。方法：将64只35日龄中国昆明鼠随机分为4组（n=16）：即Ⅰ组（空白对照组）、Ⅱ组（模型组）、Ⅲ组（Gln低剂量组）、Ⅳ组（Gin高剂量组）,Ⅱ、Ⅲ、Ⅳ组采用乙酸灌肠法人工复制小鼠溃疡性结肠炎模型,模型复制成功后Ⅰ、Ⅱ组均给予一定量的生理盐水灌服,Ⅲ、Ⅳ组分别灌服与生理盐水量相等的低（2mmol·kg^-1 bw）、高（4mmol·kg^-1 bw）两种浓度的Gln溶液,连续灌服7d后将小鼠处死。观察结肠病理组织学变化,检测血清内毒素含量,结肠组织的抗氧化水平、髓过氧化物酶（Ⅶ的）活性。结果：Gln减轻了由结肠炎造成的结肠黏膜的病理损伤,一定程度上缓解了结肠炎时血清内毒素急剧升高、结肠抗氧化水平降低及髓过氧化物酶活性升高等现象。结论：Gln对溃疡性结肠炎所致小鼠结肠损伤具有一定的修复作用。     

乳杆菌对急性溃疡性结肠炎模型小鼠的疗效观察

目的观察植物乳杆菌YXCC-1和嗜酸乳杆菌YXCC-2对小鼠急性溃疡性结肠炎(UC)的疗效。方法对这两株菌进行体外模拟胃肠环境抗性研究,并进行动物实验。采用DSS诱导的小鼠急性UC模型,将60只小鼠随机分为4组,分别为空白对照组、DSS模型组、YXCC-1组和YXCC-2组,每组15只,观察小鼠治疗前后一般情况,计算小鼠组织学损伤评分以及观察组织学病理改变。结果菌株YXCC-1、YXCC-2有一定的耐酸、耐胆盐能力,在人工肠液环境下能较好存活;灌胃菌株发酵液可显著降低UC小鼠DAI水平,明显改善结肠组织损伤。结论植物乳杆菌YXCC-1、嗜酸乳杆菌YXCC-2发酵液对小鼠溃疡性结肠炎有治疗作用,且两者疗效相当。     

Runx3在溃疡性结肠炎中的表达

目的:观察Runx3在溃疡性结肠炎(UC)粘膜组织中的表达,探讨抑癌基因RUNX3在溃疡性结肠炎发病机制中的调控作用.方法:选取经过临床表现、内镜、病理等方法共同确诊的溃疡性结肠炎活检的石蜡标本和结肠癌手术切除标本残端的正常组织石蜡标本,用免疫组织化学的方法检测Runx3蛋白在68例UC及50例对照结肠粘膜组织中的表达情况.结果:Runx3在UC及对照组结肠粘膜组织中均有表达,两者之间的差异无统计学意义(P＞0.05). Runx3的表达与UC患者的性别、年龄及病变严重程度之间无显著性相关(P＞0.05).结论:Runx3作为一个转录因子在溃疡性结肠炎的发病机制中可能通过非直接的方式发挥其重要作用.     

蒲公英多糖对溃疡性结肠炎大鼠IL-6/STAT3信号通路的影响

目的：观察蒲公英多糖对溃疡性结肠炎大鼠模型IL-6/STAT3信号通路的调控作用。方法：清洁级SD大鼠40只,雌雄各半,随机分为4组（n=10）：空白组、模型组、阳性对照组、蒲公英多糖组。采用2,4,6-三硝基苯磺酸（TNBS）诱导结肠炎大鼠模型,阳性对照组采用美沙拉嗪10 mg/kg·d灌胃,蒲公英多糖组采用蒲公英多糖10 mg/kg·d灌胃,治疗4周后处死,观察大鼠结肠粘膜病理改变,检测大鼠血清白介素-6（IL-6）含量、结肠髓过氧化物酶（MPO）、白介素-6受体（sIL-6Rα）、糖蛋白130（gp130）、转录活化因子3（STAT3）、IL-6 mRNA表达。结果：与正常组比较,模型组大鼠血清IL-6含量明显升高（P<0.01）,MPO阳性密度明显增高（P<0.01）,sIL-6Rα、gp130含量明显增高（P<0.01）,肠组织STAT3、IL-6 mRNA相对表达量明显增高（P<0.01）;与模型组比较蒲公英多糖组、美沙拉嗪组大鼠血清IL-6含量明显降低（P<0.01）,MPO阳性密度明显降低（P<0.01）,sIL-6Rα、gp130含量明显降低（P<0.01）,肠组织STAT3、IL-6 mRNA相对表达量与模型组比较明显降低（P<0.05）。结论：蒲公英多糖能够降低溃疡性结肠炎大鼠IL-6水平,下调IL-6/STAT3通路中sIL-6Rα、gp130蛋白表达量,进而下调大鼠肠组织STAT3、IL-6 mRNA的转录水平,缓解结肠组织的炎症状态,保护和修复粘膜组织,起到治疗溃疡性结肠炎的作用。     

桂皮醛对DSS诱导的溃疡性结肠炎小鼠的保护作用研究

为探讨桂皮醛(CA)对实验性溃疡性结肠炎(UC)小鼠的保护作用及其初步机制,用柳氮磺胺吡啶(300 mg/kg)做为阳性对照,CA分别以150、250、500 mg/kg的剂量对3%葡聚硫酸钠(DSS)诱导的UC小鼠进行灌胃治疗。观察小鼠给药前后状态的变化并进行DAI评分,HE染色法观察小鼠结肠组织形态的变化并进行病理评估;ELISA试剂盒、Western blot技术分别检测小鼠血清中炎症因子及小鼠结肠上皮炎症相关蛋白表达水平的变化。结果显示,与模型组比较,CA在实验剂量范围内可保护UC小鼠结肠组织形态完整,改善结肠黏膜损伤;升高血清中IL-4、IL-10含量(P<0.01),降低IL-6、IL-8及TNF-α含量(P<0.01);上调结肠组织NF-κB在胞质内表达量,并抑制STAT3磷酸化水平。综上所述,CA对UC小鼠具有保护作用,可减轻结肠组织损伤程度,抑制炎症反应,更深入的作用机制还有待进一步研究。     

Effect of hyperbaric oxygen on experimental acute distal colitis

It has been demonstrated that hyperbaric oxygen (HBO) is useful as an adjunctive therapy for Crohn's disease. However, its effects on ulcerative colitis have not been investigated. In the present study, HBO was tested for acetic acid-induced colitis, and antioxidant systems were evaluated to clarify its possible mode of action. Thirty-six Sprague-Dawley rats were randomly divided into three groups: sham control (Group I), colitis induced by acetic acid without any therapy (Group II), colitis induced by acetic acid and treated with HBO (Group III). HBO was given for 5 days, 2 sessions per day at 2.5-fold absolute atmosphere pressure (ATA) for a period of 90 min in rats in which colitis had been induced (Group III). Rats were sacrificed on the 5th day after the procedure. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH Px) activity were measured in the intestinal tissue and erythrocyte lysate. MDA and GSH Px were also determined in the plasma. Whereas MDA levels in erythrocyte, plasma and intestinal tissue were decreased, the levels of GSH Px and SOD were significantly increased in Group III as compared to those of Group II. The results of our study suggest that hyperbaric oxygen therapy has beneficial effects on the course of experimental distal colitis and that antioxidant systems may be involved in its mode of action.     

Effects of Ginkgo biloba extract on inflammatory mediators (SOD, MDA, TNF-alpha, NF-kappaBp65, IL-6) in TNBS-induced colitis in rats

Inflammatory mediators play a critical role in ulcerative colitis immune and inflammatory processes. The aim of the study was to investigate the effects of Ginkgo biloba extract on inflammatory mediators (SOD, MDA, TNF-alpha, NF-kappaBp65, IL-6) in TNBS-induced colitis in rats. Colitis in rats was induced by colonic administration with 2,4,6-trinitrobenzene sulfonic acid (TNBS, 150 mg/kg). EGB in doses of (50, 100, 200 mg/kg) was administered for 4 weeks to protect colitis. The results showed that EGB could significantly ameliorate macroscopic and histological damage, evidently elevate the activities of SOD and reduce the contents of MDA, inhibit the protein and mRNA expressions of TNF-alpha, NF-kappaBp65, and IL-6 in the colon tissues of experimental colitis in a dose-dependent manner compared with the model group. We concluded that the probable mechanisms of EGB ameliorated inflammatory injury in TNBS-induced colitis in rats by its modulation of inflammatory mediators and antioxidation.     

Effects of antioxidant therapy on leukocyte myeloperoxidase and Cu/Zn-superoxide dismutase and plasma malondialdehyde levels in experimental colitis

The aim of the present study was to evaluate the effects of N-acetylcysteine (NAC) and L-carnitine (LCAR) supplementations on polymorphonuclear leukocytes myeloperoxidase (MPO) and Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and plasma malondialdehyde (MDA) in acetic acid (AA)-induced ulcerative colitis model. The mean polymorphonuclear leukocyte MPO and Cu/Zn-SOD activity was significantly higher in the colitis group than in the control group. Both NAC and LCAR pretreatment markedly decreased MPO and Cu/Zn-SOD activity compared to colitis group. AA administration significantly increased the levels of plasma MDA in comparison with controls. However, NAC and LCAR administration to the AA-treated rats significantly reduced the MDA levels compared to colitis group. In conclusion NAC and LCAR could be beneficial agents in restoring the circulating proinflammatory mediators.     

6-姜烯酚对溃疡性结肠炎小鼠结肠上皮细胞Notch信号通路的影响

目的:观察6-姜烯酚对溃疡性结肠炎小鼠结肠上皮细胞Notch信号通路的调控作用。方法:清洁级昆明小鼠40只随机分为正常组(10只)和造模组(30只),造模组采用2%葡聚糖硫酸钠(DSS)自由饮用诱导溃疡性结肠炎模型,造模15 d后分为模型组,6-姜烯酚组,阳性对照组,每组10只。正常组、模型组灌胃生理盐水,6-姜烯酚组采用6-姜烯酚100 mg/(kg·d)灌胃,阳性对照组采用柳氮磺吡啶100 mg/(kg·d)灌胃,给药20 d后处死,观察小鼠结肠病理组织学改变,免疫荧光双标法检测结肠上皮细胞Hes-1、Math-1蛋白的表达,RT-PCR法检测结肠上皮组织Notch-1、Hes-1、Math-1 mRNA的表达,Western blot法检测结肠上皮组织Notch-1、Hes-1、Math-1蛋白的表达。结果:与正常组相比,模型组小鼠结肠上皮组织Notch-1、Hes-1蛋白和mRNA相对表达量显著升高( P＜0.01), Math-1蛋白和mRNA相对表达量显著降低( P＜0.01);与模型组比较,6-姜烯酚组、柳氮磺吡啶组小鼠结肠上皮组织Notch-1、Hes-1蛋白和mRNA相对表达量显著降低( P＜0.01), Math-1蛋白和mRNA相对表达量显著升高( P＜0.01) 。结论:6-姜烯酚能够抑制Notch通路的过度活化,调节结肠上皮吸收细胞系和分泌细胞系之间分化的平衡,修复受损结肠粘膜组织。     

Oxytocin ameliorates oxidative colonic inflammation by a neutrophil-dependent mechanism

Oxytocin (OT), a nonapeptide produced in the paraventricular and the supraoptical nuclei in the hypothalamus has a wide range of effects in the body. However, the role of OT on the gastrointestinal (GI) tract has to be settled. OT may participate in the regulation of motility, secretion, blood flow, cell turnover and release of neurotransmitters and/or peptides in the GI tract, possesses antisecretory and antiulcer effects, facilitates wound healing and is involved in the modulation of immune and inflammatory processes. The present work was conducted to assess the possible therapeutic effects of OT against the acetic acid-induced colonic injury in the rat. METHODS: Colitis was induced by intracolonic administration of acetic acid (5%) in Sprague-Dawley rats (200-250 g). Either saline or OT (0.5 mg/kg) was injected subcutaneously, immediately after the induction of colitis and repeated two times a day for 4 days. On the 4th day, rats were decapitated and distal 8 cm of the colon were removed for the macroscopic and microscopic damage scoring, determination of tissue wet weight index (WI), malondialdehyde (MDA) levels, an end product of lipid peroxidation; glutathione (GSH) levels, a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. Colonic collagen content, as a fibrosis marker was also determined. Lactate dehydrogenase (LDH) and tumor necrosis factor-alpha (TNF-alpha) levels were assayed in serum samples. In the acetic acid-induced colitis, macroscopic and microscopic damage scores, WI, MDA and MPO levels were significantly increased, while GSH levels were decreased when compared to control group (p <0.05-<0.001). Treatment with OT abolished the colitis-induced elevations in damage scores, WI, MDA and MPO levels and restored the GSH levels (p <0.05-0.001). Similarly, acetic acid increased the collagen content of colonic tissues and OT-treatment reduced this value to the level of the control group. Serum LDH and TNF-alpha levels were also elevated in the acetic acid-induced colitis group as compared to control group, while this increase was significantly decreased by OT treatment. The results suggest that OT, which improves the antioxidative state of the colonic tissue and ameliorates oxidative colonic injury via a neutrophil-dependent mechanism, requires further investigation as a potential therapeutic agent in colonic inflammation.     

Effect of adrenomedullin administration on acetic acid-induced colitis in rats

Adrenomedullin (AM) administered intracolonically ameliorated the severity of acetic acid-induced colonic ulceration in rats. Ulcers were induced by subserosal injection of acetic acid into the colon. AM-treated group was administered 0.25–1.0 μg of AM in 0.5 ml of saline intracolonically once a day; the control group received only saline. AM administration dose-dependently and significantly reduced the size of the ulcerative lesions, the associated edema, and the infiltration of the affected area by inflammatory cells. AM also reduced tissue levels of interleukin-6, but not interferon-γ. AM reduces the severity of acetic acid-induced colitis in rats, probably by inhibiting the production and/or release of Th-2 cell-derived factors such as interleukin-6.