乌梅丸联合5-氨基水杨酸治疗溃疡性结肠炎的临床研究

目的探讨乌梅丸联合5-氨基水杨酸治疗溃疡性结肠炎的临床疗效。方法选取2014年3月—2015年7月仙桃市中医医院消化内科收治的溃疡性结肠炎患者76例,按治疗方法不同分为对照组和治疗组,每组各38例。对照组口服5-氨基水杨酸肠溶片,2片/次,3次/d。治疗组在对照组治疗基础上口服乌梅丸,6丸/次,3次/d。两组患者均连续治疗6周。观察两组的临床疗效,比较治疗前后两组中医症状评分、血清炎性因子包括IL-6、IL-8、IL-10、TNF-α水平变化,同时比较两组肠道菌群的变化情况。结果治疗后,对照组和治疗组的总有效率分别为78.95%、94.74%,两组比较差异有统计学意义(P0.05)。两组患者中医症状评分、IL-6、IL-8及TNF-α均降低,IL-10显著升高,同组治疗前后差异有统计学意义(P0.05);且治疗组这些观察指标的改善程度优于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患者双歧杆菌和乳酸菌均显著升高,大肠杆菌显著降低,同组治疗前后差异具有统计学意义(P0.05);且治疗组这些观察指标的改善程度优于对照组,两组比较差异有统计学意义(P0.05)。结论乌梅丸联合5-氨基水杨酸肠溶片治疗溃疡性结肠炎具有较好的临床疗效,可降低患者临床中医症状评分,改善血清炎症细胞因子水平,促进肠道菌群恢复,具有一定的临床推广应用价值。     

5-氨基水杨酸肠溶片治疗溃疡性结肠炎

目的 :比较 5 氨基水杨酸肠溶片和柳氮磺吡啶 (SASP)治疗溃疡性结肠炎的疗效和安全性。方法 :采用随机对照、双盲双模拟的临床试验设计。试验组 2 0例病人服 5 氨基水杨酸肠溶片 ,0 .8g ,tid ;对照组 19例病人服SASP片 1g ,qid。疗程均为 6wk。结果 :试验组无效 3例 ,有效 1例 ,显效 8例 ,临床治愈 8例 ,总有效率为 80 % ;对照组无效 5例 ,有效 4例 ,显效 8例 ,临床治愈 2例 ,总有效率为5 3%。 2组不良反应发生率分别为 10 %和 2 5 %。结论 :5 氨基水杨酸肠溶片和SASP对溃疡性结肠炎具有明显治疗作用 ,前者的疗效好于后者 ,两者的安全性相似     

5-氨基水杨酸类衍生物的合成

目的 寻找活性强，副作用小的5-氨基水杨酸衍生物，本文设计并合成新的5-氨基水杨酸衍生物。方法 以水杨酸为起始原料，通过硝化、酰化、卤化反应，制得酰氯，与对乙酰氨基酚相偶联，合成了新的5-氨基水杨酸衍生物。结果 化合物的结构经红外光谱、核磁共振氢谱、碳谱及元素分析确证。结论 该合成方法成功地合成了新的5-氨基水杨酸类衍生物。     

5-氨基水杨酸治疗溃疡性结肠炎的研究进展

溃疡性结肠炎（UC）是一种病因尚不十分清楚的直肠和结肠慢性非特异性的炎症性肠病。氨基水杨酸制剂（5-ASA）用于溃疡性结肠炎的治疗已有50余年的历史，迄今为止，仍然是轻、中度UC诱导缓解与维持治疗的一线药物，但其应用的剂量、时间、剂型等方面还存在某些争议。本文将近年5-ASA在UC中的应用进展作如下综述。     

阿魏酸钠对溃疡性结肠炎患者重要炎性免疫因子的影响

目的探讨阿魏酸钠（阿魏酸钠）对溃疡性结肠炎患者血TNF-α、IL-1β、NO和PAF水平的影响及临床治疗作用。方法75例溃疡性结肠炎（UC）患者随机分为一般治疗组和阿魏酸钠治疗组。分别于治疗2周前后检测血IL-1β、TNF-α、NO和血小板活化因子（PAF）的含量。同时检测结肠过氧化物酶（MPO）活性，评价病情活动指数（CAI）与内镜分级。结果一般治疗组与阿魏酸钠治疗组升高的血IL-1β、TNF-α水平及结肠组织MPO活性均显著降低，内镜分级及CAI评分均显著改善；阿魏酸钠治疗组显著升高的血NO、PAF含量亦显著降低，而一般治疗组无明显变化。结论阿魏酸钠有效抑制UC患者多种重要炎性免疫因子，明显缓解结肠炎症反应与损伤，具有一定临床治疗效果。     

5-氨基水杨酸保留灌肠治疗慢性溃疡性结肠炎280例观察

目的探讨5-氨基水杨酸保留灌肠治疗慢性溃疡性结肠炎的临床效果。方法分别采用5-氨基水杨酸保留灌肠（0.9%NaCl-60ml＋5-氨基水杨酸制剂4 g,保留灌肠,Qd）和常规治疗法（0.9%NaCl-60ml＋氢化可的松100mg,保留灌肠,Qd）对慢性溃疡性结肠炎患者进行治疗,比较其治疗效果。结果 5-氨基水杨酸保留灌肠治疗可加快慢性溃疡性结肠炎患者粘液脓血便及腹泻症状的缓解。但对患者的腹疼症及里急后重症状的治疗,两组方法无明显差异。5-氨基水杨酸保留灌肠治疗法能够有效提高慢性溃疡性结肠炎患者的治疗有效率（其有效率为98.58%）。结论针对慢性溃疡性结肠炎患者采用5-氨基水杨酸保留灌肠治疗,可明显提高患者的治疗有效率,加快部分临床症状的缓解。     

4-氨基水杨酸钠结肠靶向微丸对溃疡性结肠炎大鼠免疫机制影响

目的 观察 4-氨基水杨酸钠(4-ASANa)结肠靶向微丸对溃疡性结肠炎大鼠的干预作用及其机制。方法 采用三硝基苯磺酸(TNBS)法制备大鼠实验性溃疡性结肠炎模型,通过4-ASANa结肠靶向微丸干预14 d,观察大鼠结肠大体形态损伤、组织学变化和白细胞介素-1B(IL-1B)、肿瘤坏死因子-α(TNF-α)、超氧化物歧化酶(SOD)、丙二醛(MDA)、髓过氧化物酶(MPO)等指标的变化。结果 4-ASANa结肠靶向微丸能减轻溃疡性结肠炎的病理损伤,显著降低溃疡性结肠炎大鼠血清IL-1B和TNF-a含量,差异具有统计学意义(P<0.05),降低结肠组织中MDA和MPO含量,而提高SOD活性,差异具有统计学意义(P<0.05),对化学因素引起的结肠炎有较好的治疗作用。结论 4-ASANa结肠靶向微丸对TNBS诱导的大鼠结肠炎具有治疗作用,抑制IL-1B和TNF-a的增殖和表达,减轻自由基的损害可能是作用机制之一。     

算盘子对溃疡性结肠炎大鼠细胞因子的影响

目的:探讨中药算盘子提取物对溃疡性结肠炎(UC)大鼠模型细胞因子的影响.方法:用5%乙酸经结肠灌注制备UC大鼠模型,分成对照组及药物组各5只,选择未出现血性腹泻的大鼠5只作为正常组,正常组和对照组每天灌服0.9% NaCl溶液2次,每次10 mL,药物组每天灌服算盘子样品液2次,每次10 mL,3周后处死,按ELISA法测定巨噬细胞中肿瘤坏死因子(TNFα)和白细胞介素 6(IL 6)的含量.结果:药物组TNFα和IL 6分别为(0.49±0.32)、(0.37±0.15) ng&#8226;mL 1,明显低于对照组,与正常组无差异.结论:中药算盘子可以显著降低UC大鼠TNFα和IL 6的水平,有治疗UC前景.     

复方阿嗪米特肠溶片联合5-氨基水杨酸治疗溃疡性结肠炎疗效观察

目的观察复方阿嗪米特肠溶片联合5-氨基水杨酸治疗溃疡性结肠炎的疗效。方法62例溃疡性结肠炎患者采用完全随机设计方法分为2组，治疗组32例，给予复方阿嗪米特肠溶片（150mg／次，3次／d，餐后立即口服）和5-氨基水杨酸（1．0g/次，4次／d）；对照组30例，给予5-氨基水杨酸（1．0／次，4次／d），疗程均2周。比较2组治疗前后腹胀、腹痛、腹泻及恶心、呕吐的改善情况。结果治疗后1周、2周时，治疗组腹胀积分明显低于对照组（P〈0．01），腹胀改善总有效率分别为81．2％和94．8％，明显高于对照组（P〈0．05）。治疗2周后，治疗组腹痛、腹泻、腹胀、恶心、呕吐等症状消失时间明显长于对照组（P〈0．05）。治疗过程中2组均未出现严重药物不良反应。结论复方阿嗪米特肠溶片联合5-氨基水杨酸治疗溃疡性结肠炎疗效非常明显，尤其腹胀症状缓解显著，两者之间具有具有协同作用。     

Protective effect of simvastatin and rosuvastatin on trinitrobenzene sulfonic acid-induced colitis in rats

Objective:Statins have anti-inflammatory effects that are not directly related to their cholesterol lowering activity. This study was carried out to evaluate the effect of simvastatin or rosuvastatin on the extent of colonic mucosal damage and on the inflammatory response in trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis.Result:Disease activity index score in TNBS-treated rats, as determined by weight loss, stool consistency, fecal occult blood, were significantly lowers in simvastatin or rosuvastatin-treated rats than TNBS-treated animals. Simvastatin or rosuvastatin counteracted the reduction in colon length, decreased colon weight, neutrophil accumulation, and tumor necrosis factor-alpha level in TNBS-induced colitis. Simvastatin and rosuvastatin also inhibited the increase in oxidative stress levels after TNBS administration.Conclusions:These results suggest that simvastatin and rosuvastatin significantly ameliorate experimental colitis in rats, and these effects could be explained by their anti-inflammatory and antioxidant activity.KEY WORDS: Rosuvastatin, simvastatin, trinitrobenzene sulfonic acid, tumor necrosis factor-α, ulcerative colitis     

康复新液缓解三硝基苯磺酸致大鼠溃疡性结肠炎及其机制研究

目的研究康复新液对三硝基苯磺酸诱导大鼠溃疡性结肠炎的作用,并初步探讨其作用机制。方法将♂SD大鼠分为正常组、模型组、柳氮磺胺吡啶组和康复新液低、中、高剂量组,以三硝基苯磺酸灌肠诱导大鼠溃疡性结肠炎模型。评估疾病活动指数(DAI)、结肠黏膜损伤指数(CMDI)和病理组织学评分(HS),测定脏器指数、血清IL-4、IL-17,结肠黏膜MPO、EGF、TGF-β1的表达水平等。结果 DAI结果提示造模成功,与正常组比较,模型组IL-4、IL-17、EGF、TGF-β1均明显降低,而CMDI、HS、结肠指数及结肠黏膜MPO均明显升高。康复新液各组DAI、CMDI、HS、结肠黏膜MPO均降低(P<0.05或P<0.01),IL-4、IL-17、EGF、TGF-β1水平明显升高(P<0.01)。结论康复新液灌肠能够有效缓解三硝基苯磺酸诱导的大鼠溃疡性结肠炎,其作用机制可能与下调MPO表达,上调IL-4、IL-17、EGF和TGF-β1水平有关。     

地塞米松当归多糖前体药对三硝基苯磺酸诱导的大鼠溃疡性结肠炎的治疗作用

目的:探讨地塞米松当归多糖前体药(dexam-ethasone Angelica sinensis polysaccharide prodrug,DEX-AP)对三硝基苯磺酸(TNBS)诱导的溃疡性结肠炎(ulcerative colitis,UC)的治疗作用及副作用。方法:采用TNBS的45%乙醇溶液(50 mg.ml-1)灌肠诱导实验性UC大鼠模型,分别采用0.25μmol.kg-1.d-1地塞米松(DEX)及0.05、0.25、1.25μmol.kg-1.d-1DEX-AP(以地塞米松含量计)灌胃治疗7 d。检测外周血淋巴细胞数后处死动物,取肾脏、脾脏和结肠称重。计算结肠溃疡面积后,取部分结肠粘膜组织测髓过氧化物酶(myeloperoxidase,MPO)活性,部分结肠组织制作石蜡切片,HE染色后进行光镜观察。结果:TNBS诱导的UC大鼠经0.05、0.25、1.25μmol.kg-1.d-1DEX-AP治疗7 d后,与模型组比较,DEX组结肠重量未见明显变化,而DEX-AP各组结肠重量均明显降低(P<0.05);DEX组与DEX-AP各组的结肠组织MPO酶活性均显著降低,且DEX-AP降低MPO酶活性具有剂量依赖性。0.25μmol.kg-1.d-1DEX使UC大鼠外周血淋巴细胞数、胸腺及脾脏重量均显著降低(P<0.01);0.05、0.25μmol.kg-1.d-1DEX-AP对UC大鼠外周血淋巴细胞数、胸腺及脾脏重量未见明显影响(P>0.05);1.25μmol.kg-1.d-1DEX-AP对脾脏重量未见明显影响,却使胸腺重量及外周血淋巴细胞数降低,但仍显著高于0.25μmol.kg-1.d-1DEX组(P<0.01)。UC大鼠经1.25μmol.kg-1.d-1DEX-AP治疗后,结肠粘膜组织结构基本恢复正常。结论:DEX-AP对TNBS诱导的实验性UC大鼠具有显著的治疗作用,且副作用低,具有良好的应用前景。     

Olmesartan medoxomil self-microemulsifying drug delivery system reverses apoptosis and improves cell adhesion in trinitrobenzene sulfonic acid-induced colitis in rats

Olmesartan medoxomil (OM) is an angiotensin receptor blocker. This study aimed to investigate the effects of OM self-microemulsifying drug delivery system (OMS) in trinitrobenzene sulfonic acid (TNBS)-induced acute colitis in rats. Besides two control groups, five TNBS-colitic-treated groups (n = 8) were given orally sulfasalazine (100 mg/kg/day), low and high doses of OM (3.0 and 10.0 mg/kg/day) (OML and OMH) and of OMS (OMSL and OMSH) for seven days. A colitis activity score was calculated. The colon was examined macroscopically. Colonic levels of myeloperoxidase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde, and reduced glutathione were measured. Plasma and colonic olmesartan levels were measured. Colonic sections were subjected to hematoxylin and eosin staining and immunohistochemical staining for E-cadherin, caspase-3, and matrix metalloproteinase-9 (MMP-9). Protein expression of E-cadherin, Bcl-2 associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2), and cleaved caspase-3 by Western blot was done. TNBS-colitic rats showed increased colonic myeloperoxidase, TNF-α, IL-6, and malondialdehyde, decreased colonic glutathione, histopathological, immunohistochemical, and protein expression alterations. OMS, compared with OM, dose-dependently achieved higher colonic free olmesartan concentration, showed better anti-inflammatory, antioxidant, and anti-apoptotic effects, improved intestinal barrier, and decreased mucolytic activity. OMS more effectively up-regulated the reduced Bcl-2, Bcl-2/Bax ratio, and E-cadherin expression, and down-regulated the overexpressed Bax, cleaved caspase-3, and MMP-9. OMSL exerted effects comparable to OMH. Sulfasalazine exerted maximal colonic protective effects and almost completely reversed colonic damage, and OMSH showed nearly similar effects with non-significant differences in-between or compared with the normal control group. In conclusion, OMS could be a potential additive treatment for Crohn''s disease colitis.     

芝麻素对2,4,6-三硝基苯磺酸诱导的大鼠溃疡性结肠炎的影响

目的研究芝麻素对2,4,6-三硝基苯磺酸（TNBS）诱导的大鼠溃疡性结肠炎（UC）的保护作用。方法 Wistar大鼠50只,随机分为空白对照组,模型组和芝麻素低、中、高剂量5组,每组10只。用TNBS/乙醇灌肠法复制大鼠UC模型,芝麻素组分别给与不同剂量芝麻素进行灌胃治疗,10 d后处死全部大鼠,收集血液和结肠标本,ELISA法检测血清中IL-6、IL-10和TNF-α含量以及生化法检测结肠组织中髓过氧化物酶（MPO）、超氧化物歧化酶（SOD）活力以及一氧化氮（NO）、还原性谷胱甘肽（GSH）、丙二醛（MDA）含量。结果与模型组比较,芝麻素3个剂量组以及空白对照组血清TNF-α、IL-6含量显著降低,IL-10含量显著升高,差异有统计学意义（P〈0.01或P〈0.05）。与模型组相比,芝麻素3个剂量组以及空白对照组MPO活力及NO和MDA含量均降低,SOD活力与GSH含量升高,差异有统计学意义（P〈0.01）。结论芝麻素可通过提高结肠炎大鼠结肠组织抗氧化能力,调节结肠炎大鼠血清炎性细胞因子的平衡,抑制NO生成,发挥治疗作用。     

Galanin in the trinitrobenzene sulfonic acid rat model of experimental colitis

Neuropeptides are molecules produced by a variety of cells that modulate several biological processes and modify the activity of cells responsible either to trigger tissue damage and to promote healing in the intestine. Galanin is a neuropeptide present in enteric nerves lining the gastrointestinal tract and involved in the secretion and contractility regulation. The aim of this study is to investigate its potential therapeutic experimental use in an immunological disorder, such as experimental trinitrobenzensulfonic acid (TNBS)-induced colitis in rats. Galanin (10, 20 and 40 microg/kg/day) was administered by intraperitoneal route 48, 24 and 1 h prior to the induction of colitis and 24 h later, and the animals were sacrificed 48 h after. The lesions were blindly scored according to macroscopic and histological scales. The inflammatory response was assessed by histological analysis and by myeloperoxidase activity (MPO) and tumour necrosis factor-alpha (TNF-alpha) production. The results indicated that Galanin prevented the morphological alteration and reduced ulcer index associated with TNBS. In addition, Galanin reduced MPO and TNF-alpha values significantly. In order to elucidate some of the mechanisms, cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression was analyzed by Western blotting. COX-2 was not modified, but iNOS protein was significantly reduced accompanied by a diminished nitrite production, in a dose-dependent manner, in comparison to the TNBS group. In conclusion, Galanin treatment has a significant preventive effect in the TNBS-induced acute model of colitis with reduction of the analyzed inflammatory parameters. Moreover, the results obtained demonstrated by the first time that Galanin administration promotes an important reduction in NO-related mechanisms.     

黄芩素对2,4,6-三硝基苯磺酸诱导的小鼠实验性肠炎的作用和机制

目的探讨黄芩素对2,4,6-三硝基苯磺酸(TNBS)诱导的小鼠肠炎实验模型的作用及机制。方法将BALB/c小鼠随机分成3组(n=10):正常对照组、模型组(TNBS)和黄芩素组(TNBS+黄芩素20 mg·kg-1)。黄芩素组于造模前2 d ig给予黄芩素,每天1次,共9 d。测量结肠长度,并取结肠组织进行HE染色,进行组织损伤和炎症细胞浸润评分;ELISA测定结肠组织中肿瘤坏死因子α(TNF-α)含量。体外制备细菌脂多糖(LPS)诱导的RAW264.7炎症细胞模型,黄芩素(10,25和50 mmol·L-1)给药干预,Griess试剂法测定上清中一氧化氮(NO)含量;荧光定量PCR检测炎症介质TNF-α、白细胞介素6(IL-6)、IL-1β、诱导型NO合酶(i NOS)、环氧合酶2(COX-2)和单核细胞趋化蛋白1(MCP-1)m RNA表达;Western蛋白印迹法检测磷脂酰肌醇3-激酶/蛋白激酶B/NF-κB(PI3K/AKT/NF-κB)通路磷酸化蛋白(p-PI3K,p-AKT,p-p65和p-IκBa)表达。结果与正常对照组相比,模型组小鼠结肠缩短,组织病理损伤,炎症细胞浸润,组织TNF-α含量增高;黄芩素给药组上述症状得到显著改善(P<0.05)。与细胞对照组相比,LPS模型组细胞NO分泌、炎症介质(TNF-α,IL-6,IL-1β,i NOS,COX-2和MCP-1)m RNA表达及PI3K/AKT/NF-κB通路磷酸化蛋白表达均增高(P<0.05,P<0.01);与模型组比较,黄芩素给药组上述指标均降低(P<0.05,P<0.01)。结论黄芩素可减轻TNBS诱导的小鼠实验性肠炎的症状,作用机制可能与抑制PI3K/AKT/NF-κB通路的激活从而抑制炎症介质的表达和减少炎症因子释放有关。     

选择性环氧合酶-2抑制剂对大鼠溃疡性结肠炎作用的实验研究

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）诱导的大鼠溃疡性结肠炎的作用，并初步探讨其作用机制。方法将大鼠分为三组，第1组和第2组为造模组，用0．25ml TNBS乙醇溶液（TNBS浓度25mg／ml，乙醇浓度50％），灌肠，诱导大鼠实验性溃疡性结肠炎模型。造模组大鼠于造模前3h开始，分别给予塞来昔布（12．5mg／kg）和蒸馏水（1mL／0．3mg），2次／d，共7d。第3组为正常对照组。第7d实验结束时处死所用存活动物，观察结肠黏膜损伤程度，并用ELISA法检测IL-1β、IL-10、TNF-β的浓度。结果造模组结肠损伤积分为（8．20±1．96）（第1组）和（12．05±2．30）（第2组）均显著高于正常对照组（0．64±0．15）（P值均〈0．01）。第1组的结肠损伤积分显著低于第2组（P〈0．05）。第1组中IL-1β、TNF-β的表达分别为（5．27±1．13）pg／ml、（5．12±1．62）pg／ml较第2组的（6．76±2．01）pg／ml、（7．96±2．12）pg／ml低（P〈0．05），但均高于正常对照组；而IL-10的表达第1组为（2．38±0．31）pg／ml较第2组（1．56±0．84）pg／ml高（P〈0．05），均低于正常对照组。结论选择性COX-2抑制剂塞来昔布使大鼠实验性溃疡性结肠炎损伤减轻，对IL-1β、IL-10、TNF-β的表达有不同的影响。     

Thromboxane A2 up-regulates neutrophil elastase release in Syrian hamsters with trinitrobenzene sulfonic acid-induced colitis

Neutrophil elastase (NE) is a factor that aggravates colitis. We investigated the influence of thromboxane A2 (TXA2) and leukotriene B4 (LTB4) on NE release in Syrian hamsters with trinitrobenzene sulfonic acid-induced colitis. Colonic specimens with colitis were incubated with U-46619 (a TXA2 analogue) or LTB4 in vitro and NE release was examined. As a result, U-46619 increased NE release, while LTB4 had no effect. The NE release induced by U-46619 was inhibited by a TP-receptor antagonist. To demonstrate that TXA2 caused NE release in vivo as well, while LTB4 did not, colitis animals were treated with nordihydroguaiaretic acid (NDGA), a dual inhibitor of cyclooxygenase/lipoxygenase; and colonic luminal TXB(A)2 and LTB4 levels and NE activity were determined. The TXB(A)2 level was significantly correlated with NE activity, while no correlation was found between LTB4 and NE activity. An inhibitory effect of NDGA on the ulcer area was also observed, and NE activity was significantly correlated with the ulcer area. The suppression of TXA2 production by NDGA may result in the inhibition of NE release so that colonic tissue damage becomes less severe. Regulation of NE release is a new biological action of TXA2 that has not been reported before.