徐长卿对三硝基苯磺酸诱导的大鼠结肠炎的作用

目的:探讨徐长卿对2,4,6-三硝基苯磺酸(trinitrobenzenesulfonic acid,TNBS)诱导的大鼠结肠炎的作用.方法:将40只♂SD大鼠随机分为4组:正常组、模型组、徐长卿组和巴柳氮组.除正常组外,其余3组大鼠均以TNBS灌肠造模.灌肠24h后,徐长卿组开始每天给予徐长卿4g/kg;巴柳氮组给予巴柳氮钠1g/kg灌胃治疗10d.每天观察大鼠一般情况,给药结束后,观察大鼠结肠大体损伤及病理,酵素免疫分析法(enzyme-linked immunosorbant assay,ELISA)检测肠组织肿瘤坏死因子(tumor necrosis factor,TNF)-α、白介素(interleukin,IL)-1β及IL-10水平.结果:两治疗组体质量较模型组增加,但差异无统计学意义;两治疗组疾病活动指数(disease activity index,DAI)评分较模型组明显下降(0.70±1.06,0.67±0.71vs2.38±1.51,P<0.05).徐长卿组、巴柳氮组结肠大体损伤及病理评分较模型组显著下降(1.05±0.83,1.06±0.85vs2.94±0.94;1.65±1.67,2.00±1.80vs6.00±1.67,均P<0.01).徐长卿组较模型组TNF-α、IL-1β水平明显降低(P<0.01),IL-10水平无统计学差异.巴柳氮组较模型组TNF-α、IL-1β、IL-10水平均明显降低(P<0.01).结论:徐长卿能有效改善TNBS诱导的大鼠结肠炎,其机制可能与调节细胞因子水平有关.     

金属蛋白酶抑制剂对大鼠结肠炎的作用研究

炎症性肠病（IBD）包括溃疡性结肠炎（UC）和克罗恩病（CD）,为非特异性肠道炎症,其病程迁延,治疗困难.最近研究提示,IBD炎症组织中基质金属蛋白酶（MMP）表达增高,且MMP抑制剂（MMPI）治疗一些胃肠道疾病有一定疗效[1],但对慢性肠道黏膜炎症的治疗尚鲜见报道.本研究拟采用三硝基苯磺酸（TNBS）二次致炎法,建立急、慢性结肠炎共存的动物模型,检测MMPI--二氮杂菲防治TNBS肠炎的作用,并与传统的柳氮磺胺吡啶（SASP）比较,希望能为IBD的治疗提供新的思路和途径.     

三硝基苯磺酸结肠炎动物模型的建立

建立三硝基本磺酸（TNBS）诱导的结肠炎动物模型,探讨炎症性肠病（IBD）的发病机制。方法：每只实验组大鼠用0．85ml含30mgTNBS的50％乙醇灌肠1次诱发远端结肠炎,对照组大鼠仅以505乙醇或TNBS盐水溶液灌肠。观察结肠大体形态和组织学改变,并检测肠粘膜髓过氧化物酶（MPO）活性。 结果：灌肠后第1－3周,实验组大鼠远端结肠表现为朗血、水肿及溃疡形成,组织学以中性粒细胞浸润主为：第4－8周,溃疡农渐愈合,组织学表现为淋巴细胞和浆细胞浸润,组织学改变及MPO活必在第1周即恢复正常,结论：LTNBS／乙醇诱导大鼠远端结肠炎是一种较 IBD动物模,可作为研究IBD发机制及评估药物疗效的有益工具。     

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。     

姜黄素对三硝基苯磺酸诱导的结肠炎模型细胞因子的影响

目的探讨姜黄素对三硝基苯磺酸(TNBS)诱导的实验性结肠炎的疗效,并研究肠黏膜、脾细胞和血清中细胞因子的变化。方法45只Sprague-Dawley大鼠经直肠注入TNBS(100 mg/kg)诱导肠炎模型。实验动物分为阴性对照组、模型组(TNBS)和姜黄素治疗组(30 mg·kg~(-1)·d~(-1),腹腔注射)。RT-PCR测定肠黏膜细胞因子表达水平,流式细胞术测定脾细胞内干扰素(IFN)-γ和白细胞介素(IL)-4,ELISA法测定血清中IFN-γ和IL-4。结果姜黄素治疗前后肠黏膜大体评分(3．9±1．0比2．2±0．7),髓过氧化物酶(MPO)活性[每毫克蛋白(15．0±2．6)U比(7．3±1．4)U],肠黏膜中Th1类细胞因子IFN-0γ(1．02±0．07比0．06±0．02)、IL-12 mRNA相对表达水平(0．29±0．05比0．11±0．01)和IFN-γ/IL-4比值(11．44±0．97比0．38±0．10),脾细胞中IFN-γCD4~+细胞百分比(31．7±7．5比21．1±3．7)和IFN-γ/IL-4 CD4~+比值(19．9±5．1比6．1±1．8),血清中IFN-γ质量浓度[(1528±159)pg/ml比(513±14)pg/ml]和IFN-γ/IL-4比值(19．5±4．1比4．2±0．6)均降低(P＜0．05或P＜0．01)。且姜黄素治疗前后肠黏膜中Th2类细胞因子IL-4 mRNA(0．09±0．01比0．15±0．04)和IL-10 mRNA相对表达水平(0．28±0．08比0．63±0．12),脾细胞中IL-4 CD4~+细胞百分比(1．6±0．5比3．4±1．1)和血清IL-4质量浓度[(81±1 5)pg/ml比(124±20)pg/ml]升高(P＜0．05或P＜0．01)。结论姜黄素能治疗TNBS诱导的肠炎,其机制可能与调节肠道局部和机体Th1/Th2平衡有关。     

雷帕霉素在大鼠实验性三硝基苯磺酸结肠炎发病中的作用

目的 观察转录激活因子3(STAT3)特异性抑制剂雷帕霉素(RPM)对大鼠实验性三硝基苯磺酸结肠炎的作用,以及对基质金属蛋白酶(MMPs)、基质金属蛋白酶组织抑制剂(TIMPs)表达的影响,探讨信号转导和转录激活因子-3(STAT3)信号转导通路在大鼠结肠炎发病机制中的作用.方法 建实验性大鼠结肠炎模型后,给予RPM腹腔注射治疗一周后处死大鼠,观察结肠炎症改变并做出评分,SYBR Green Ⅰ实时荧光定量RT-PCR检测结肠组织MMP-1、MMP-2、MMP-3、TIMP-1及TIMP-2的mRNA表达.结果 RPM治疗组肠道损伤积分为(5.17±1.80),低于对照组(P<0.05);MMP-1、MMP-2的mRNA表达量在RPM组均明显降低(P<0.05),而MMP-3、TIMP-1和TIMP-2 mRNA表达无明显差异(P>0.05).结论 RPM通过阻断STAT3信号通路的活化能缓解大鼠结肠炎的病情,这一作用可能是通过抑制MMP-1和MMP-2的表达实现的.     

三硝基苯磺酸诱导小鼠溃疡性结肠炎模型制备的技术改良

目的:改良2,4,6-三硝基苯磺酸(TNBS)硅胶管灌肠诱导制备小鼠溃疡性结肠炎(UC)模型的方法,提高造模的成功率和模型的稳定性,并探索造模的适宜剂量和时间.方法:选用40只SPF级♂Balb/c小鼠,6-8周龄,随机分为正常对照组、不同浓度TNBS组(37.5mg/kg、75mg/kg、150mg/kg、200mg/k g),每组8只,使用灌胃针替代硅胶管灌肠,并于灌肠后2d和4d分别处死4只小鼠,观察不同组别小鼠生理状态、结肠组织的损伤及病理学的改变情况.结果:在灌胃针造模过程中未发生小鼠死亡现象;对照组小鼠一般情况及结肠黏膜组织无异常改变;小鼠灌肠后出现少食、少动、体质量下降、皮毛光泽度下降、腹泻、便血.不同浓度TNBS造模组随着TNBS剂量的增加,小鼠结肠黏膜组织出现充血、出血、水肿、炎症、溃疡的程度增加.HE染色可见结肠组织水肿、炎症细胞浸润、杯状细胞缺失、溃疡形成的程度逐渐增加.其中TNBS37.5mg/kg、75mg/kg组于造模后2d,以上损伤现象开始缓解,未形成稳定的UC模型;150mg/kg、200mg/kg组持续时间较长,以上损伤现象4d内未见明显缓解,150mg/kg组表现为较典型的UC模型,200mg/kg为重症UC模型.结论:对制造小鼠UC模型进行相关技术改进,使灌肠更加简便,提高造模效率,显著增加了模型的稳定性.     

维生素D3对三硝基苯磺酸诱导的大鼠结肠炎的作用

背景:维生素D(VitD)对炎症性肠病(IBD)的免疫调节作用日渐受到关注。目的:探讨VitD3对TNBS诱导的大鼠结肠炎的疗效及其机制。方法:66只雄性大鼠随机分为11组:空白对照组、TNBS组、5-ASA组、不同剂量VitD3组及其联合5-ASA组、活性VitD3组及其联合5-ASA组。除空白对照组外,其余10组以TNBS灌肠诱导结肠炎模型。造模后24 h,各组以不同药物灌胃进行干预。造模第10 d处死大鼠,评估疾病活动指数(DAI)、大体损伤、组织病理学评分,测定髓过氧化物酶(MPO)活性,以RT-PCR法检测T-bet、GATA-3 mRNA表达。测定血钙和血肌酐水平以监测不良反应。结果:与TNBS组相比,单次和连续大剂量VitD3联合5-ASA组大体损伤评分和组织病理学评分均明显下降(P<0.05);各药物干预组MPO活性均明显下降(P<0.001),T-bet mRNA表达无明显差异;5-ASA组、连续大剂量VitD3组GATA-3 mRNA表达明显升高(P<0.05)。连续大剂量VitD3组及其联合5-ASA组大鼠出现高钙血症,且连续大剂量VitD3组血肌酐水平明显高于其余各组(P<0.05)。结论:VitD3可通过调节T细胞免疫减轻TNBS诱导的实验性结肠炎。     

康复新液对急性大鼠实验性结肠炎作用机制的研究

康复新液在临床上对溃疡性结肠炎（UC）具有良好疗效，但其具体机制尚不明确。基质金属蛋白酶（MMPs）是细胞外基质（ECM）合成和降解的关键酶，与UC的发生、发展密切相关。目的：探讨康复新液对葡聚糖硫酸钠（DSS）诱导的急性大鼠实验性结肠炎的疗效和对MMPs表达的影响。方法：30只健康雄性Sprague-Dawley大鼠随机分为正常对照组、模型组和康复新液治疗组。模型组和康复新液治疗组大鼠以3％DSS溶液制备急性大鼠实验性结肠炎模型。第10d处死大鼠，测定各组大鼠疾病活动指数（DAI）、组织学损伤评分和肠组织髓过氧化物酶（MPO）活性；以MMPs功能基因芯片检测筛选表达差异的基因，并行荧光定量聚合酶链反应（PCR）验证。结果：与模型组相比，康复新液治疗组大鼠DAI和组织学损伤评分显著降低（P〈0．01），MPO活性显著降低（P〈0．01）。康复新液治疗组表达差异在2倍或以上的基因有16个，PCR结果显示MMP-3、MMP-13表达较模型组降低（P〈0．01），与芯片变化趋势一致。结论：康复新液可改善DSS诱导的急性大鼠实验性结肠炎，减轻腹泻、血便症状。康复新液抑制MMP-3、MMP-13表达可能是其作用机制之一。     

垂盆草对实验性结肠炎的保护作用及其机制研究

[目的]观察垂盆草干预三硝基苯磺酸(TNBS)诱导的结肠炎模型大鼠转化生长因子β1(TGF-β1)、白细胞介素2(IL-2)、IL-10的改变,探讨垂盆草是否对结肠炎具有保护作用及其可能作用机制。[方法]30只SD大鼠随机分为3组;模型组及干预组经肛灌入TNBS/乙醇,对照组灌入0.85%氯化钠。造模后干预组给予垂盆草灌胃,对照组及模型组给予0.85%氯化钠,检测炎症活动指数(DAI)、大体形态损伤指数(CMDI)、组织学损伤指数(TDI)的改变,免疫组化检测结肠TGF-β1的表达,ElISA法检测血清IL-2、IL-10。[结果]干预组结肠TGF-β1表达平均光密度(0.21±0.02)较模型组(0.19±0.01)升高;干预组血清IL-10浓度(34.00±6.56)pg/ml较模型组(27.61±4.28)pg/ml升高;干预组血清IL-2浓度(66.70±3.51)pg/ml较模型组(66.70±3.51)pg/ml降低(均P<0.05)。干预组大鼠的DAI、CMDI及TDI与模型组比较差异有统计学意义(均P<0.05)。[结论]垂盆草对TN-BS诱导的实验性结肠炎具有保护作用,可能通过调控T细胞分泌TGF-β1、IL-2、IL-10等细胞因子发挥作用。     

Therapeutic effect of the immunomodulator glatiramer acetate on trinitrobenzene sulfonic acid-induced experimental colitis

Inflammatory bowel diseases are characterized by detrimental immune reactivity in the gut and imbalance between proinflammatory and antiinflammatory reactivity. In an attempt to downregulate inflammatory bowel disease, we tested whether the immunomodulator glatiramer acetate (GA; Copaxone, copolymer 1), an approved drug for the treatment of multiple sclerosis, can ameliorate trinitrobenzene sulfonic acid (TNBS)-induced colitis, a murine model that resembles human Crohn's disease. Experimental colitis was induced by rectal instillation of TNBS in 3 mice strains: BALB/c, SJL/J, and (SJL/JXBALB/c)F1, and its severity was evaluated by gross colon injury, histologic damage, body weight, and survival rate. We studied the effect of GA on all these parameters as well as on lymphocyte reactivity manifested by proliferation and secretion of tumor necrosis factor-alpha, and transforming growth factor-beta. GA treatment significantly suppressed the various manifestations of TNBS-induced colitis as demonstrated by substantial reduction in the macroscopic colonic damage, preservation of the microscopic colonic structure, reduced weight loss, and improved long-term survival, in GA treated mice compared with untreated mice. The parenteral route was more effective than the oral route. GA suppressed the proliferation of local mesenteric lymphocytes to syngeneic colon extract and the detrimental tumor necrosis factor-alpha secretion. In addition, it induced a beneficial secretion of transforming growth factor-beta. The ability of GA to effectively modulate the clinical manifestations and the detrimental immune response involved in experimental colitis warrants further studies to determine the clinical efficacy of GA in the treatment of human inflammatory bowel diseases.     

Effect of argatroban on trinitrobenzene sulfonic acid-induced colitis

BACKGROUND: Recent studies have suggested that heparin is effective for treatment of inflammatory bowel disease (IBD) and its various effects (in addition to the anticoagulant effect). We evaluated the effects of argatroban as an antithrombin drug on trinitrobenzene sulfonic acid (TNB)-induced colitis, an established model of IBD. METHODS: Rats were randomly assigned to four groups in which mini-osmotic pumps containing saline (TNB-S), argatroban (TNB-A), or 100 U/kg heparin (TNB-H) were intraperitoneally implanted. Three days after the pumps were implanted, TNB was infused via the anus, and colitis was induced. After 5 days, prothrombin time (PT), activated partial prothrombin time (APTT), antithrombin III (AT-III), platelet, fibrinogen, colonic wet weight, macroscopic damage score, histological score, mucosal myeloperoxidase activity and mucosal leukotrien B4 (LTB4) levels were compared among the four groups. RESULTS: The APTT was prolonged in the heparin treatment group but only slightly prolonged in the argatroban treatment group. The platelet count and the fibrinogen level were higher in the TNB-S group than in the healthy control group and the AT-III level was slightly lower in the TNB-S group than in the healthy control group and lower still in the TNB-H group. CONCLUSIONS: The colonic wet weight was similar among the four groups while the macroscopic damage score, histological score, mucosal myeloperoxidase activity and the mucosal LTB4 level were significantly decreased in the TNB-A and TNB-H groups. Argatroban, as well as heparin may be effective for treatment of TNB-induced colitis.     

Hepcidin expression in colon during trinitrobenzene sulfonic acid-induced colitis in rats

AIM:To investigate hepcidin expression,interleukin-6(IL-6)production and iron levels in the rat colon in the presence of trinitrobenzene sulfonic acid(TNBS)-induced colitis.METHODS:In rats,we evaluated the severity of colitis induced by repeated TNBS administration using macroscopic and microscopic scoring systems and myeloperoxidase activity measurements.The colonic levels of hepcidin,tumor necrosis factor alpha(TNF-α),IL-10 and IL-6 were measured by Enzyme-Linked Immunosorbent Assay,and hepcidin-25 expression and iron deposition were analyzed by immunohistochemistry and the Prussian blue reaction,respectively.Stat-3 phosphorylation was assessed by Western blot analysis.Hematological parameters,iron and transferrin levels,and transferrin saturation were also measured.Additionally,the ability of iron,pathogen-derived molecules and IL-6 to induce hepcidin expression in HT-29 cells was evaluated.RESULTS:Repeated TNBS administration to rats resulted in macroscopically and microscopically detectable colon lesions and elevated colonic myeloperoxidase activity.Hepcidin-25 protein levels were increased in colonic surface epithelia in colitic rats(10.2±4.0pg/mg protein vs 71.0±8.4 pg/mg protein,P<0.01).Elevated IL-6 levels(8.2±1.7 pg/mg protein vs 14.7±0.7 pg/mg protein,P<0.05),TNF-αlevels(1.8±1.2pg/mg protein vs 7.4±2.1 pg/mg protein,P<0.05)and Stat-3 phosphorylation were also observed.Systemic alterations in iron homeostasis,hepcidin levels and anemia were not detected in colitic rats.Iron deposition in the colon was only observed during colitis.Hepcidin gene expression was increased in HT-29 cells after IL-6 and lipopolysaccharide[a toll-like receptor 4(TLR-4)ligand]treatment.Deferoxamine,ferric citrate and peptidoglycan(a TLR-2 ligand)were unable to alter the in vitro expression of hepcidin in HT-29 cells.CONCLUSION:Colitis increased local hepcidin-25 expression,which was associated with the IL-6/Stat-3 signaling pathway.An increase in local iron sequestration was also observed,but additional studies are needed to determine whether this sequestration is a defensive or pathological response to intestinal inflammation.     

白芍总甙对大鼠实验性结肠炎Th17细胞相关因子的作用

目的:观察白芍总甙(TGP)对实验性结肠炎干预的治疗效果,探讨TGP对实验性结肠炎的抗炎作用.方法:40RSD大鼠以三硝基苯磺酸(TNBS)/醇溶液灌肠诱导结肠炎模型,均分为结肠炎模型组、正常对照组(0.9%NaCl溶液灌肠)、TGP组(100mg/kg)和5-ASA药物对照组(100mg/kg).连续灌胃14 d后行结肠大体损伤指数(CMDI)和组织学损伤指数(TDI)评分,ELISA检测血清IL-6、IL-17及IL-23水平,免疫组织化学SP法检测结肠组织TGF-β1与Foxp3的表达.结果:与结肠炎模型组相比,正常组CMDI、TDI,血清IL-6,IL-17及IL-23含量明显低,结肠组织TGF-β1和Foxp3含量明显高.5-ASA与TGP能显著降低CMDI和TDI(2.78分±2.11分,3.56分±1.94分 vs 6.88分±0.84分,均P<0.05;2.22分±0.83分,2.44分±1.51分 vs 5.63分±0.74分,均P<0.05),降低血清IL-6,IL-17和IL-23含量(5-ASA:t=5.998,2.438,2.670,均P<0.05;TGP:t=5.203,3.013,2.962,均P<0.05).升高结肠组织中TGF-β1和Foxp3(5-ASA:t=6.026,3.022,均P<0.05;TGP:t=6.198,2.734,均P<0.05).TGP组与5-ASA组无明显统计学差异.结论:TGP可能通过上调TGF-β1和Foxp3水平,促进Treg细胞的表达,抑制Th17细胞群的活化,下调IL-6,IL-17和IL-23的表达,减轻TNBS诱导的大鼠实验性结肠炎的症状和结肠炎性损伤.     

青藤碱对结肠炎大鼠基质金属蛋白激酶的作用

目的:研究青藤碱对三硝基苯磺酸诱导的实验性结肠炎的防治作用.方法:三硝基苯磺酸/乙醇制备大鼠结肠炎模型,40只SD大鼠随机均分为正常组、模型组、5-ASA组及青藤碱治疗组.正常组与模型组每天每只给予生理盐水2 mL,5-ASA组给予5-ASA 100 mg/(kg·d),青藤碱组给予青藤碱120 mg/(kg·d),连续灌胃14 d.评价各组大鼠结肠大体形态损伤指数(CMDI)和组织学损伤指数(TDI),ELISA法检测血清TNF-α、MMP-2和MMP-9含量,免疫组织化学法检测结肠组织MMP-2和MMP-9的表达.结果:模型组大鼠CMDI、TDI,血清TNF-α、MMP-2和MMP-9含量,结肠组织MMP-2和MMP-9表达均显著高于正常组(均P<0.01),5-ASA和青藤碱能明显减弱CMDI和TDI(1.30±1.16,1.00±0.82 vs 6.50±1.27;1.10±1.20,0.90±0.99 vs 5.10±0.74,均P<0.01),降低血清TNF-α、MMP-2和MMP-9含量及结肠组织MMP-2和MMP-9的表达(35.37±4.44,32.50±4.91 vs 74.72±5.30;2.44±0.83,2.50±0.82 vs 10.40±2.10;5.88±1.84,5.32±1.81 vs15.85±2.39;1.30±1.25,1.00±0.94 vs 5.00±1.41;1.50±1.35,1.40±0.97 vs 6.30±0.67;均P<0.01),5-ASA组与青藤碱组差异无显著统计学意义.结论:青藤碱能明显降低结肠炎大鼠TNF-α、MMP-2和MMP-9的表达,对大鼠结肠炎发挥良好的抗炎作用.     

Skeletal muscle catabolism in trinitrobenzene sulfonic acid-induced murine colitis

The present study determined whether the muscle atrophy produced by colitis is associated with altered rates of muscle protein synthesis or degradation, as well as the potential role of the local (eg, muscle) insulin-like growth factor (IGF) system and muscle-specific ubiquitin E3 ligases atrogin-1 and MuRF1 in mediating altered muscle protein balance. Colitis was induced in C57BL/6 mice by intrarectal administration of trinitrobenzene sulfonic acid (TNBS), and blood and tissues were collected on day 10. Mice with inflammatory bowel disease demonstrated reduced skeletal muscle mass and protein content, whereas colonic segment weight and gross damage score were both increased in mice with colitis, compared with time-matched control values. There was no change in muscle protein synthesis in mice with inflammatory bowel disease; but there was an increased protein breakdown (45%), proteasome activity (85%), and messenger RNA (mRNA) expression for atrogin-1 and MuRF1 (200%-300%) in muscle. These changes were associated with a reduction in liver (but not muscle) IGF-I mRNA as well as a reduction in both total and free IGF-I in the blood. Colitis decreased the hepatic content of IGF binding protein (IGFBP)-3 mRNA by 40% and increased IGFBP-1 mRNA by 100%. In contrast, colitis did alter IGFBP mRNAs in muscle. The tumor necrosis factor-α, interleukin-6, and nitric oxide synthase 2 mRNA content of both liver and skeletal muscle was increased in TNBS-treated mice; and plasma tumor necrosis factor-α and interleukin-6 concentrations were also elevated. These data suggest that TNBS-induced colitis is independent of a change in muscle protein synthesis but dependent on stimulation of protein degradation via increased expression of muscle-specific atrogenes, which may be mediated in part by the reduction in circulating concentration of IGF-I and the concomitant increase in inflammatory mediators observed in the blood and muscle per se.     

清肠栓调节三硝基苯磺酸诱导结肠炎大鼠结肠黏膜细胞增殖的影响

[目的]从细胞增殖动力学角度探讨清肠栓促进结肠溃疡愈合的作用机制.[方法]制备三硝基苯磺酸(TNBS)诱导结肠炎大鼠.造模3 d,分为清肠栓高剂量组、清肠栓低剂量组、柳氮磺胺吡啶(SASP)组、模型对照组、模型组和正常组.给药7 d后,取大鼠结肠病变部位标本,进行组织学评价,运用AB-PAS染色观察杯状细胞数量及其分泌黏液功能,免疫组化染色法检测增殖细胞核抗原(PCNA)表达.[结果]与清肠栓低剂量组、SASP组、模型对照组和正常组比较,清肠栓高剂量组大鼠结肠黏膜炎症消除和溃疡愈合,杯状细胞数量及黏液增加,溃疡边缘腺体细胞增殖加强,PCNA表达增加(P＜0.05).[结论]清肠栓具有促进结肠炎大鼠结肠黏膜细胞增殖、增加杯状细胞的数量和分泌黏液的水平等作用,能够促进结肠溃疡愈合过程.     

Proteome profiling of spinal cord and dorsal root ganglia in rats with trinitrobenzene sulfonic acid-induced colitis

AIM: To investigate proteomic changes in spinal cord and dorsal root ganglia (DRG) of rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis.METHODS: The colonic myeloperoxidase (MPO) activity and tumor necrosis factor-α (TNF-α) level were determined. A two-dimensional electrophoresis (2-DE)-based proteomic technique was used to profile the global protein expression changes in the DRG and spinal cord of the rats with acute colitis induced by intra-colonic injection of TNBS.RESULTS: TNBS group showed significantly elevated colonic MPO activity and increased TNF-α level. The proteins derived from lumbosacral enlargement of the spinal cord and DRG were resolved by 2-DE; and 26 and 19 proteins that displayed significantly different expression levels in the DRG and spinal cord were identified respectively. Altered proteins were found to be involved in a number of biological functions, such as inflammation/immunity, cell signaling, redox regulation, sulfate transport and cellular metabolism. The overexpression of the protein similar to potassium channel tetramerisation domain containing protein 12 (Kctd 12) and low expression of proteasome subunit α type-1 (psma) were validated by Western blotting analysis.CONCLUSION: TNBS-induced colitis has a profound impact on protein profiling in the nervous system. This result helps understand the neurological pathogenesis of inflammatory bowel disease.     

The effect of recombinant human growth hormone (rhGH) on trinitrobenzene sulfonic acid-induced colitis in rats: an experimental study

The limited efficacy of standard medical therapies for inflammatory bowel diseases has resulted in a continuing search for alternative treatments. Growth hormone (GH) has shown to have mutagenic and proliferative effects on intestinal cells. This study was designed to identify the effect of growth hormone on trinitrobenzene slfonic acid-induced colitis (TNBSIC) in rats. This study was carried out on 30 rats, divided in 3 groups: group 1: TNBSIC+ GH, group 2: TNBSIC, group 3: saline enema. Colitis was induced in male Sprague-Dawley rats (200 g-250 g) by intracolonic installation of 2, 4, 6-trinitrobenzene sulphonic acid in 50% ethanol. GH treatment has been started and continued throughout the study after inducing colitis. All rats were killed after 5 weeks and colonic segments were examined histopathologically. Microscopic and macroscopic damage scores were caulculated. Intestinal damage scores were found higher in Goups II when compared with treatment group (P < 0.05). There was no damage in group 3 as expected. Both macroscopic and microscopic scores were highest in group 2 (P < 0.05). The myloperoxidase activity was found lower comparing to group 2 (P < 0.05). In conclusion, growth hormone replacement had protective effects against colonic inflammation while reducing intestinal damage on TNB-induced colitis.