溃疡性结肠炎和克罗恩病临床特点的比较分析

目的：比较分析溃疡性结肠炎和克罗恩病的临床特点。方法：将本院2009年2～11月收治的48例炎症性肠病患者按照疾病种类分为溃疡性结肠炎组33例和克罗恩病组15例,总结两组患者的临床特点,并进行比较。结果：溃疡性结肠炎患者明显多于克罗恩病患者,前者的发病年龄及并发症发生率均明显高于后者,组间差异均具有统计学意义（P〈0.001或P〈0.05）,且两组患者的临床症状间差异也有统计学意义（P〈0.05）。结论：炎症性肠病中,溃疡性结肠炎更为常见,其发病年龄及并发症发生率高于克罗恩病,两种疾病的临床表现多样。     

芒果苷滴丸对小鼠实验性肝损伤的保护作用

目的：研究芒果苷滴丸（MDP）对小鼠实验性肝损伤的保护作用及其机制。方法：以MDP对小鼠灌胃给药,对MDP进行最大耐受量（MTD）测定;采用四氯化碳（CCl4）、D-氨基半乳糖盐酸盐（D—GaIN）诱导小鼠急性肝损伤模型;卡介苗（BCG）加脂多糖（LPS）联合诱导小鼠免疫性肝损伤模型。分光光度法检测血清中丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）含量和肝组织匀浆中超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH—Px）含量,苏木精-伊红（HE）染色法对肝脏组织作病理切片法检查。结果：①以MDP对小鼠灌胃给药,其MTD为180g·kg^-1,相当于原药材36g·kg^-1。②MDP能显著降低急性、免疫性肝损伤小鼠血清中ALT、AST含量（P〈0．01）,能降低急性肝损伤小鼠肝匀浆MDA含量（P〈0．01）,升高肝匀浆SOD、GSH—PX活性（P〈0．01）,病理结果表明MDP能减轻免疫性小鼠肝损伤的肝损伤程度。结论：MDP对急性、免疫性肝损伤小鼠具有显著保护作用,其作用机制可能与抗脂质过氧化有关。     

化学诱导型结肠炎动物模型的研究进展

实验动物模型对于发现抗炎症性肠病的药物及探讨其发病机制具有重要作用。通过文献查阅,综述了目前用于炎症性肠病药理学研究的化学诱导型结肠炎动物模型的研究进展,从制备方法、模型特征、可能的致病机制和用途等方面进行了详细的论述。对于认知和了解炎症性肠病的发病机制及在实验中对IBD实验动物模型的选择提供一定的依据。     

芒果苷滴丸对大鼠慢性肝损伤的保护作用

目的:研究芒果苷滴丸(MDP)对大鼠慢性肝损伤的保护作用并探讨其机制.方法:四氯化碳(CCl4)诱导大鼠慢性肝损伤模型;分光光度法检测血清中ALT、AST、总蛋白(TP)、白蛋白(ALB)、羟脯氨酸(HyP)水平和肝组织匀浆中SOD、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)等含量,放免法检测血清中透明质酸(HA)、Ⅲ型前胶原(PCⅢ)水平,免疫组化法检测肝组织转化生长因子β1(TGF-β1)的表达,苏木精-伊红(HE)染色法对肝脏组织作病理切片法检查.结果:MDP能显著降低四氯化碳(CCl4)所致大鼠慢性肝损血清中ALT、AST、HA、PCⅢ、HyP、ALB、TP含量(P<0.01或P<0.05),升高肝组织中SOD、GSH-PX的活性(P<0.01或P<0.05),降低MDA的含量(P<0.01或P<0.05);抑制TGF-β1表达;减轻慢性肝损伤的损伤程度.结论:MDP对慢性肝损伤大鼠具有显著保护作用,其作用机制可能与抗脂质过氧化和肝组织转化生长因子-β1(TGF-β1)的表达有关.     

枫蓼提取物对小鼠实验性溃疡性结肠炎的防治作用

目的探讨枫蓼提取物对小鼠溃疡性结肠炎的防治作用。方法通过小肠推进实验和番泻叶致小鼠腹泻模型观察小肠推进率、稀便率及腹泻指数。用4%葡聚糖硫酸钠(DSS)建立小鼠溃疡性结肠炎模型,对正常组、模型组、美沙拉嗪组、枫蓼提取物11.7,23.4和46.8 g·kg-1剂量组小鼠进行疾病活动指数(DAI)评分,测定结肠组织中白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)、丙二醛(MDA)和一氧化氮(NO)含量及髓过氧化物酶(MPO)的活性。结果枫蓼提取物46.8 g·kg-1能抑制小鼠小肠推进率,显著减少番泻叶致腹泻小鼠腹泻次数,降低腹泻率和腹泻指数(P<0.05)。结肠炎结果显示,与正常组比较,模型组小鼠体质量减轻,DAI评分增高(P<0.05),结肠组织中MPO活性、IL-1β、TNF-α、MDA和NO含量升高(P<0.01)。与模型组比较,枫蓼提取物46.8 g·kg-1组小鼠DAI评分降低29.1%(P<0.05);23.4和46.8 g·kg-1组结肠组织中MPO活性、TNF-α、MDA和NO含量均降低(P<0.05)。结论枫蓼提取物能改善DSS诱导小鼠溃疡性结肠炎,可能与解痉、止泻、抗炎、抗氧化及减少炎性介质释放等有关。     

乌梅水煎物对实验性溃疡性结肠炎小鼠的作用

目的探讨乌梅对溃疡性结肠炎(UC)小鼠结肠组织过氧化物歧化酶(SOD)活性及丙二醛(MDA)含量的影响。方法采用3%葡聚糖硫酸钠(DSS)溶液给小鼠自由饮水,建立小鼠溃疡性结肠炎模型,造模成功后,正常组、模型组给予0.33 ml生理盐水灌胃,乌梅低、中、高剂量组分别按设计剂量灌胃,每天1次,均连续给药10 d,期间进行隐血试验和观察粪便性状以及进行疾病活动度(DAI)评分;肉眼观察结合显微镜观察结肠组织形态学评分;测定病变结肠组织中SOD活性与MDA含量。结果发现乌梅中、高剂量组的小鼠无肉眼血便,可见松散大便。乌梅低、中、高剂量组的DAI均降低,中、高剂量组与模型组比较具有极显著性差异(P<0.01),在结肠黏膜病理改变中,乌梅高剂量组黏膜糜烂不严重,溃疡小,黏膜充血、水肿程度轻;在测定的SOD活力值中,中、高剂量组与模型组比较具有极显著性差异(P<0.01),均明显高于模型组。中剂量组与正常组比较具有显著性差异(P<0.05),高剂量组与正常组比较无显著性差异。测得MDA含量中,中、高剂量组与模型组比较具有极显著性差异(P<0.01),均明显低于模型组。结论提示自由基与UC的结肠组织损伤密切相关,参考UC的病理过程,乌梅对UC有明显治疗效果,并可能通过提高病变组织的SOD活性与降低MDA含量来发挥治疗作用。     

美沙拉嗪治疗溃疡性结肠炎的临床疗效观察

炎症性肠病(inflammatory bowel disease,IBD)包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD),是慢性肠道炎症性疾病,发病机制复杂,至今尚未完全明确,目前普遍认为是环境因素作用于遗传易感者,在肠道菌群的参与下,启动了肠道免疫及非免疫系统,最终导致免疫反应和炎症过程。UC是一种只累及大     

异荭草苷对葡聚糖硫酸钠诱导溃疡性结肠炎小鼠的治疗作用及其机制

目的:研究异荭草苷(isoorientin, ISO)对葡聚糖硫酸钠(dextran sulfate sodium, DSS)诱导小鼠慢性溃疡性结肠炎(ulcerative colitis, UC)的保护作用。方法:将40只C57BL/6小鼠随机分为对照组、DSS组(2%DSS)、美沙拉嗪(5-ASA, 150 mg·kg^-1·d^-1)+DSS组、低剂量ISO(L-ISO, 10 mg·kg^-1·d^-1)+DSS组和高剂量ISO(H-ISO, 20 mg·kg^-1·d^-1)+DSS组,每组各8只。ISO灌胃治疗37 d后采用脊椎脱臼的方式处死小鼠,收集结肠组织并记录其长度。苏木精-伊红(HE)染色观察小鼠结肠组织病理变化,ELISA法测定结肠组织中炎性细胞因子的含量,阿利新蓝-过碘酸雪夫(AB-PAS)染色观察小鼠结肠组织黏蛋白分泌情况,透射电镜观察结肠黏膜超微结构变化,免疫印迹法检测小鼠结肠组织中P-糖蛋白表达水平。结果:与DSS组相比,ISO显著改善D...     

Thymoquinone protects against experimental colitis in rats

The present work was done to investigate the possible effects of thymoquinone on acetic acid-induced colitis in rats. Colitis was induced by intracolonic injection of 3% acetic acid. Several parameters including macroscopic score, histopathological and biochemical, were determined to assess the degree of protection. Biochemical parameters such as myeloperoxidase activity, reduced glutathione levels, platelet activating factor (PAF) and histamine were measured following standard assay procedures. The study showed that pretreatment of rats for 3 days with thymoquinone (10 mg/kg) was able to give complete protection against acetic acid-induced colitis an effect significantly higher than sulfasalazine (500 mg/kg) control group. The smaller dose of thymoquinone (5 mg/kg) produced partial protection. Moreover, the biochemical and histopathological changes were reversed and brought towards the control. These results suggest a beneficial effect of thymoquinone against experimentally-induced colitis and the possible mechanism of the protective effects may be partly due to an antioxidant action.     

Targeting Toll-like receptors by chloroquine protects mice from experimental cerebral malaria

Excessive production of proinflammatory cytokines, elicited mostly by Th1 cells, is an important cause of cerebral malaria (CM). Dendritic cells (DCs), a critical link between innate and adaptive immune responses, rely heavily on Toll-like receptor (TLR) signaling. Using C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) as an experimental CM model, we first confirmed that inhibition of TLR9 by suppressive oligodeoxynucleotides protected mice from CM. In addition to being a well-known antimalarial, chloroquine (CQ) has been used as an immunomodulator of endocytic TLRs because it inhibits endosomal acidification. We found that immediately before and shortly after infection by PbA, treatment with a single dose of 50 mg/kg of CQ protected mice from experimental CM. Both CQ treatments significantly inhibited expression of TLR9 and MHC-II on DCs, and reduced the number of myeloid and plasmatocytoid DCs at 3 and 5 days after infection. Consequently, activation of CD4+ T cells, especially the expansion of the Th1 subsets, was dramatically inhibited in CQ treated groups, which was accompanied by a remarkable decline in the production of Th1 type proinflammatory mediators IFN-γ, TNF-α, and nitric oxide. Taken together, these results corroborated the involvement of TLR9 in CM pathogenesis and suggest that interference with the activation of this receptor is a promising strategy to prevent deleterious inflammatory response mediating pathogenesis and severity of malaria.     

Mangiferin corrects the imbalance of Th17/Treg cells in mice with TNBS-induced colitis

In the previous study, 80% ethanol extract of the rhizome mixture of Anemarrhena asphodeloides and Coptidis chinensis (AC) and its main constituent mangiferin improved TNBS-induced colitis in mice by inhibiting macrophage activation related to the innate immunity. In the preliminary study, we found that AC could inhibit Th17 cell differentiation in mice with TNBS-induced colitis. Therefore, we investigated whether AC and it main constituent mangiferin are capable of inhibiting inflammation by regulating T cell differentiation related to the adaptive immunity in vitro and in vivo. AC and mangiferin potently suppressed colon shortening and myeloperoxidase activity in mice with TNBS-induced colitis. They also suppressed TNBS-induced Th17 cell differentiation and IL-17 expression, but increased TNBS-suppressed Treg cell differentiation and IL-10 expression. Moreover, AC and mangiferin strongly inhibited the expression of TNF-α and IL-17, as well as the activation of NF-κB. Furthermore, mangiferin potently inhibited the differentiation of splenocytes into Th7 cells and increased the differentiation into Treg cells in vitro. Mangiferin also inhibited RORγt and IL-17 expression and STAT3 activation in splenocytes and induced Foxp3 and IL-10 expression and STAT5 activation. Based on these findings, mangiferin may ameliorate colitis by the restoration of disturbed Th17/Treg cells and inhibition of macrophage activation.     

Polymeric inhibitor of influenza virus attachment protects mice from experimental influenza infection

Synthetic sialic acid-containing macromolecules inhibit influenza virus attachment to target cells and suppress the virus-mediated hemagglutination and neutralize virus infectivity in cell culture. To test the protective effects of attachment inhibitors in vivo, mice were infected with mouse-adapted influenza virus A/Aichi/2/68 (H3N2) and treated with synthetic polyacrylamide-based sialylglycopolymer PAA-YDS bearing moieties of (Neu5Acalpha2-6Galbeta1-4GlcNAcbeta1-2Manalpha1)2-3,6Manbeta1-4GlcNAcbeta1-4GlcNAc. Single intranasal inoculations with PAA-YDS 30 min before or 10 min after infection increased the survival of mice (P<0.01). Multiple treatments with aerosolized PAA-YDS on days 2-5 post infection also increased survival (P<0.01), alleviated disease symptoms, and decreased lesions in the mouse lungs. These data suggest that synthetic polyvalent inhibitors of virus attachment can be used for prevention and treatment of influenza.     

Dandelion root extract protects NCM460 colonic cells and relieves experimental mouse colitis

The protective potential of dandelion on acute hepatitis, lung injury and colorectal cancer has recently been revealed. Importantly, ulcerative colitis (UC), a clinically defined inflammatory bowel disease, accelerates the risk of colorectal cancer. However, studies focusing on the activity of dandelion on UC are extremely limited. In the present study, we found that an aqueous extract of dandelion root increases cell viability and decreases apoptosis in dextran sodium sulfate (DSS)-incubated NCM460 human colonic epithelial cells, probably through removing the production of reaction oxygen species and blocking nuclear factor-kappaB signaling. We then examined the anti-colitis efficacy of this extract in an in vivo study. We detected that dandelion root extract efficiently ameliorates progressive acute injury as demonstrated by a reduction in body weight loss, severity scores of disease index and shortened colon length during DSS treatment, as well as reducing the inflammatory conditions and oxidative stress in the colon of DSS-induced mice. Our study clearly demonstrates that dandelion has a strong cytoprotective effect on NCM460 colonocytes and shows powerful defense on an established experimental mouse model of DSS-induced UC. Therefore, dandelion root extract can be an effective anti-colitis complex mixture and can provide a complementary alternative to currently available therapeutic intervention in UC.     

Tauroursodeoxycholate improves 2,4,6-trinitrobenzenesulfonic acid-induced experimental acute ulcerative colitis in mice

Ulcerative colitis is a chronic nonspecific inflammatory disease of unknown cause. The aim of this study was to evaluate the anti-inflammatory effect of tauroursodeoxycholate in 2, 4, 6-trinitrobenzenesulfonic acid-induced experimental colitis in mice. After the induction of colitis for 24 h, the mice were administrated orally with tauroursodeoxycholate (20, 40 and 60 mg/kg) and sulfasalazine (500 mg/kg) by gavage for 7 consecutive days. The inhibition effects were evaluated by the body of weight change, survival rate, macroscopical and histological evaluations. Besides, myeloperoxidase (MPO) activity, interleukin (IL)-1β, interferon (IFN)-γ and tumour necrosis factor-α (TNF-α) in colon tissue were also determined by enzyme-linked immunosorbent assay. Treatment with different doses of tauroursodeoxycholate (20, 40 and 60 mg/kg) significantly improved the body weight change, decreased the macroscopic and histopathological scores. Compared with the model group, the accumulation of MPO activity, the colonic tissue levels of IL-1β, IFN-γ and TNF-α were significantly reduced in the tauroursodeoxycholate treated groups. Moreover, tauroursodeoxycholate assuaged the symptoms of colitis. These results suggested that tauroursodeoxycholate has an anti-inflammatory effect in TNBS-induced ulcerative colitis in mice.     

三硝基苯磺酸诱导Balb/c小鼠结肠炎的实验研究

目的建立三硝基苯磺酸(TNBS)小鼠结肠炎模型。方法采用不同剂量的TNBS给♀Balb/c小鼠灌肠后制备结肠炎模型。观察动物的存活率、疾病活动度指数、结肠肉眼观和组织学变化,并检测结肠组织中髓过氧化物酶(MPO)的活力及小鼠脾T淋巴细胞增殖情况。结果随着TNBS剂量的提高,模型组小鼠存活率下降。存活的多数小鼠疾病活动度指数及MPO活力升高,病理切片显示结肠固有层及粘膜下层有大量淋巴细胞、单核巨噬细胞以及中性白细胞浸润,伴有肠腺扭曲、减少,杯状细胞丢失,隐窝脓肿,血管增生,肠壁增厚等病理改变,表明均建立了慢性结肠炎模型。结论每只小鼠给予1.5mgTNBS灌肠,动物死亡较少,并能够成功制备小鼠结肠炎模型。     

Effect of dehydroleucodine in experimental colitis in rats and mice.

Dehydroleucodine (DhL), a sesquiterpene lactone (SQL) of the guaianolide type isolated from Artemisia douglasiana Besser, shows a pharmacological cytoprotective effect and significantly prevents the formation of gastric and duodenal lesions induced by various necrotising agents in rodents. The effects of DhL, on two models of experimental colitis were examined. Colitis was produced in male Wistar rats by rectal instillation of 5 and 10% acetic acid, following the methods of Eliakim et al. and Le Duc et al., respectively. In mice colitis was produced by rectal instillation of 0.1 ml of 2,4,6-trinitrobenzene sulphonic acid (5 mg in 50% ethanol) (TNB) as previously described by Chin et al. In this study, the administration of DhL 40 mg kg(-1)(1 h before the induction of colitis) significantly decreased mucosal damage. This effect was consistent in both models. The protection provided by DhL was accompanied by significant decreases in diarrhoea and colon weight; and histologically normal mucosa without ulceration and mucus production were observed. This study shows that both TNB and acetic acid colitis can be pharmacologically controlled by DhL. Our results suggest that the protective activity of DhL in experimental colitis is mediated, at least in part, through the increase of glycoprotein synthesis, anti-inflammatory effect and inhibition of COX-2 induction, and by inhibiting the degranulation of cells containing monoamines.     

Polyphenol extract from evening primrose pomace alleviates experimental colitis after intracolonic and oral administration in mice

Oenothera paradoxa (EP) preparations are commonly used in folk medicine to treat skin diseases, neuralgia, and gastrointestinal (GI) disorders. Several reports suggested that EP preparations exhibit potent anti-inflammatory and antioxidant activities both in vitro and in vivo. Here, we aimed to characterize the action of EP pomace polyphenol extract in mouse model of colitis. We analyzed the composition of EP pomace polyphenol extract using reversed phase HPLC system and ultra-performance liquid chromatography (UPLC) system coupled with a quadrupole-time of flight (Q-TOF) MS instrument. Then, we used a well-established animal model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis to determine the anti-inflammatory action of EP pomace polyphenol extract. We also investigated the effect of the EP pomace polyphenol extract on pro-inflammatory (IL-1β and TNF-α) cytokine mRNA levels and hydrogen peroxide concentration in the inflamed colon. Administration of EP pomace polyphenol extract significantly improved macroscopic and microscopic damage scores, as well as myeloperoxidase (MPO) activity in TNBS-treated mice. The anti-inflammatory effect of the extract was observed after intracolonic and oral administration and was dose-dependent. Significant reduction of tissue hydrogen peroxide level after treatment with EP pomace polyphenol extract suggests that its therapeutic effect is a result of free radical scavenging. This novel finding indicates that the application of the EP pomace polyphenol extract in patients with inflammatory bowel diseases (IBDs) may become an attractive supplementary treatment for conventional anti-inflammatory therapy.     

Genistein treatment protects mice from ionizing radiation injury

The radioprotective and behavioral effects of an acute administration of the isoflavone genistein (4',5,7-trihydroxyflavone) were investigated in adult CD2F1 male mice. Mice were administered a single subcutaneous (s.c.) dose of genistein either 24 h or 1 h before a lethal dose of gamma radiation (9.5-Gy of cobalt-60 at 0.6 Gy min(-1)). Mice received saline, PEG-400 vehicle or genistein at 3.125, 6.25, 12.5, 25, 50, 100, 200, or 400 mg kg(-1) body weight. For mice treated 24 h before irradiation there was a significant increase in 30-day survival for animals receiving genistein doses of 25 to 400 mg kg(-1) (p<0.001). In contrast, the 30-day survival rates of mice treated with genistein 1 h before irradiation were not significantly different from those of the vehicle control group. Additionally, the acute toxicity of genistein was evaluated in non-irradiated male mice administered a single s.c. injection of saline, vehicle, or genistein at 100, 200 or 400 mg kg(-1). At these genistein doses there were no adverse effects, compared with controls, on locomotor activity, grip strength, motor coordination, body weight, testes weight, or histopathology. These results demonstrate that a single s.c. administration of the flavonoid genistein at non-toxic doses provides protection against acute radiation injury.