巴柳氮二钠的合成

目的合成巴柳氮二钠并改进工艺。方法以对硝基苯甲酰氯为起始原料,经缩合,还原、重氮化、偶合、成盐等反应制得巴柳氮二钠。结果所得产物经元素分析、紫外光谱、红外光谱、核磁共振谱及质谱等确证了结构。结论合成路线可行。     

2,4-二硝基氯苯在致敏试验中剂量方法的探讨

2，4-二硝基氯苯是一种淡黄色或黄棕色针状结晶，有苦杏仁味，分子式为：C6H3CIN2O4。主要用于医药、农药、合成染料和化学助剂等原料。而在农药、消毒产品的毒理学试验时，2，4-二硝基氯苯主要用于在皮肤变态（致敏）反应毒性试验中，作为该方法可靠检查的阳性对照物。在此试验中，我们采用少量体积分数为95％的乙醇溶解该阳性物后，再用水稀释，此方法简单，可获得较好的阳性结果。     

美沙拉嗪缓释剂对2，4，6-三硝基苯磺酸诱导大鼠溃疡性结肠炎的治疗作用

目的 研究美沙拉嗪缓释剂对2,4,6 三硝基苯磺酸(2,4,6-trinitro picrylsulfonic acid,TNBS)诱导的溃疡性结肠炎肿瘤坏死因子α(tumor necrosis factor α,TNF-α)、白细胞介素(interleukin,IL) 1β、IL-6表达的影响,探讨美沙拉嗪缓释剂的抗炎机制. 方法 应用TNBS/乙醇建立大鼠溃疡性结肠炎模型,实验设正常对照组、模型组、药物治疗组(给予美沙拉嗪溶液100 mg&#8226;kg^-1&#8226;d^-1), 阳性对照组(给予5-对氨基水杨酸100 mg&#8226;kg^-1&#8226;d^-1),每组10只,每天灌胃2次,给药时间从造模后第1天开始至实验结束,共7 d,观察大鼠疾病活动指数(disease index,DAI)、体质量变化及结肠病理学改变,生化法检查大鼠结肠组织髓过氧化物酶(myeloperoxidase,MPO)活性,逆转录聚合酶链反应(Real-time PCR)检测肠组织TNF-α、IL-1β、IL-6mRNA的表达水平. 结果 与正常对照组比较,模型组大鼠结肠组织MPO活性及TNF-α、IL-1β、IL-6mRNA表达量明显增多(P<0.05).与模型组和阳性对照组比较,药物治疗组MPO活性及结肠组织TNF-α、IL-1β、IL-6mRNA的表达明显减少(P<0.05).模型组和阳性对照组差异无统计学意义. 结论 美沙拉嗪缓释剂对大鼠实验性溃疡性结肠炎具有治疗作用,其机制与通过降低中性粒细胞的浸润、抑制促炎因子TNF-α、IL-1β、IL-6mRNA等的表达有关.     

血清白细胞介素-2和白细胞介素-4在糖尿病肾病早期诊断中的意义

目的 分析血清白细胞介素(IL)-2和IL-4在糖尿病肾病(DN)早期诊断中的价值.方法 选取DN患者60例(DN组)、糖尿病患者60例(DM组)和健康体检者60例(对照组),检测其血清IL-2和IL-4水平.结果 各组在性别、年龄、体质量指数(BMI)、收缩压(SBP)、舒张压(DBP)上比较,均差异无统计学意义(P>0.05).DN组患者尿肌酐(UCr)、血肌酐(SCr)均高于其他两组,均差异有统计学意义(P<0.05).DN组患者IL-2水平明显低于DM组和对照组,而IL-4水平却高于DM组和对照组.IL-2和IL-4单独作为标记物诊断急性肾衰竭(AKI)时,ROC曲线下面积(AUC)分别为:0.833和0.952(P<0.01),二者联合诊断时,诊断率为100%.结论 临床中应用单一的生物学标志物进行诊断DN诊断价值较低.但是,联合各项生物学标志物进行检测可以相互弥补,提高DN的诊断准确率,有助于临床工作者早期发现DN,提供有效的干预措施,减少病死率.     

二硝基氯苯致敏溃疡性结肠炎大鼠细胞因子活性研究

目的：探讨二硝基氯苯（DNCB）致敏联合醋酸灌肠法对溃疡性结肠炎（UC）模型大鼠细胞因子的影响.方法：采用二硝基氯苯致敏联合醋酸灌肠法及醋酸灌肠法对SD大鼠进行溃疡性结肠炎造模,并做对比研究.SD大鼠随机分为复合造模组、醋酸造模组、空白对照组.空白组作为各项指标对照,各组均予生理盐水灌胃治疗,分别在第1、15和29d取样观测大鼠的一般情况变化、结肠组织黏膜损伤评分（CMDI）、病理组织学评分（TDI）,检测血清IL-2、IL-4、IL-6、IL-10、IL-17、IL-23等细胞因子水平,并对各组细胞因子与黏膜评分及病理评分进行相关性比较.结果：IL-2：与对照组比较,复合组（第1d、第15 d）和醋酸组（第1d）显著降低;而复合组第15 d与醋酸组第15 d比较显著降低.IL-6：与对照组及醋酸组（第1d）比较,复合组（第1 d）显著升高.IL-10：与对照组比较,复合组（第1d、第15 d）和醋酸组（第1d、第15 d、第29 d）显著降低;IL-17：与对照组比较,复合组（第1d、第15 d）和醋酸组（第1d）显著降低;而醋酸组（第15d）与复合组（第15 d）比较显著升高.CMDI：与对照组比较,各组均有显著升高.TDI：与对照组比较,醋酸（第1d）、复合（第1d）有显著升高.相关性：IL-2、IL-10、IL-17与CMDI明显相关;IL-2与TDI明显相关.结论：二硝基氯苯致敏联合醋酸灌肠法及醋酸灌肠法均能造成SD大鼠溃疡性结肠炎,与醋酸灌肠法比较,二硝基氯苯致敏联合醋酸灌肠法有可能通过下调IL-2,上调IL-6、IL-17,从而加重和延长大鼠免疫紊乱的状态.     

己烯雌酚对2、4、6-三硝基苯磺酸/乙醇诱导的大鼠结肠炎的影响

目的:观察己烯雌酚对2、4、6-三硝基苯磺酸(trinitrobenzene sulfonic,TNBS)/乙醇诱导的大鼠结肠炎的双向调节作用。方法:TNBS诱导大鼠结肠炎模型,肌肉注射己烯雌酚(50、100、150、200μg.kg-1),每天1次,共7 d。给药结束后,乙醚麻醉大鼠,打开腹腔,截取8 cm结肠,称重,画取溃疡面积,取病变组织以作HE染色,分离肠粘膜待测MPO活性;并取胸腺、脾脏称量。结果:50μg.kg-1己烯雌酚对结肠炎无明显治疗作用,反而引起肠道粘连和腹膜炎,加重炎症;100μg.kg-1的己烯雌酚对结肠炎具明显疗效;150和200μg.kg-1己烯雌酚能明显改善结肠炎各项指标,但大鼠全身状态差,死亡率增高。结论:适当剂量的己烯雌酚对结肠炎具有治疗作用,小剂量的己烯雌酚能够加重结肠炎的发生。     

清热利湿健脾方对溃疡性结肠炎模型大鼠的保护作用

目的:研究清热利湿健脾方对溃疡性结肠炎模型大鼠的保护作用。方法:于大鼠肛门内灌注三硝基苯磺酸(100 mg/kg)以复制溃疡性结肠炎模型。75只Wistar大鼠随机均分为正常对照(等容生理盐水)组、模型(等容生理盐水)组、柳氮磺胺吡啶(0.27 g/kg)组与清热利湿健脾方高、低剂量(15.00、7.50 g/kg)组,灌胃给药,每天1次,连续20 d。观察大鼠活动以评定疾病活动指数(DAI),检测大鼠血清与结肠中白细胞介素(IL)-6、IL-10含量与超氧化物歧化酶(SOD)活性。结果:与正常对照组比较,模型组大鼠DAI升高,IL-6含量增加,IL-10含量减少,SOD活性减弱,差异有统计学意义(P<0.05);与模型组比较,清热利湿健脾方高、低剂量组大鼠DAI降低,IL-6含量减少,IL-10含量增加,SOD活性增强,差异有统计学意义(P<0.05)。结论:清热利湿健脾方通过降低炎性因子,增加抑炎因子含量和增强SOD活性起到对溃疡性结肠炎模型大鼠的保护作用。     

实验性结肠炎中移动抑制因子活性的神经调节

目的观察移动抑制因子(MIF)在实验性结肠炎的肠壁神经组织中的表达,探讨肠神经系统对结肠炎中MIF活性的调控作用。方法以半抗原二硝基氯苯(DNCB)给经过致敏的大鼠和小鼠灌肠诱发结肠炎,用二苯基四氮唑溴盐(MTT)法测定肠系膜淋巴细胞中MIF活性、用免疫荧光双染方法测定肠神经元中MIF蛋白的表达,观察ip6-羟基多巴(6-OHDA)和体外去甲肾上腺素(NE)培养对结肠炎时MIF活性的影响。结果结肠炎大鼠肠壁神经元MIF蛋白的表达随DNCB灌肠剂量的增大而增强;6-OHDA(38～150mg·kg-1体重)能够进一步刺激结肠炎小鼠MIF活性的升高(ip6-OHDA组与ip溶剂的结肠炎组相比,P<0.01);NE(1.0nmol·L-1～1.0mmol·L-1)体外可使结肠炎组的MIF活性升高,其反应幅度和敏感性大于对照组(两组相比,P<0.01)。结论DNCB引起的实验性结肠炎中MIF活性升高;正常的交感活动能够抑制结肠炎时的MIF活性。     

胃乐散对溃疡大鼠免疫球蛋白、IL-2及IL-4的影响

目的观察胃乐散对实验性溃疡大鼠的免疫球蛋白及白细胞介素2(IL-2)、白细胞介素4(IL-4)的影响,并探讨其作用机制。方法取SD大鼠48只,随机均分为正常组、模型组、胃乐散低、中、高剂量组和雷尼替丁组,采用冰醋酸烧灼法制备大鼠的胃溃疡模型。连续用药14 d后,处死大鼠,取血清,用ELISA法检测血清中IL-2、IL-4,用免疫比浊法测量血清中免疫球蛋白IgG、IgA、IgM水平的变化。结果模型组大鼠的IL-2、IL-4明显低于正常组。与模型组比较,胃乐散能提高大鼠的IL-2、IL-4的水平(P<0.05),也能增加血清中IgG、IgA、IgM的含量(P<0.05)。结论胃乐散治疗胃溃疡的机制之一可能与提高机体的细胞免疫和体液免疫有关。     

2，4-噻唑二酮的合成

以硫脲和氯乙酸忆酯为原料,经环合、中和,得到2-亚胺基-4-噻唑酮,然后用20%盐酸水解,合成了目标物2,4-噻唑二酮,总收率为61%,该方法未见文献报道。     

巴柳氮治疗轻、中度溃疡性结肠炎24例

目的：观察巴柳氮胶囊治疗轻、中度溃疡性结肠炎(UC)的临床疗效和安全性。方法：采用随机、双盲、双模拟及阳性药物平行对照方案,将46例UC病人随机分为巴柳氮胶囊试验组(24例,6.75 g·d~(-1))和柳氮磺吡啶(SASP)对照组(22例,3 g·d~(-1)),疗程均为8 wk。对2组病人治疗前后的临床症状、肠镜检查及不良反应情况进行比较。结果：试验组总有效率为96%,明显高于对照组45%(P＜0.01)。试验组不良反应发生率低于对照组(4%比36%,P＜0.05)。结论：巴柳氮胶囊治疗轻、中度急性发作性溃疡性结肠炎是安全、有效的,适用于SASP耐受性差的UC病人。     

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。     

黄连水煎液对实验性大鼠溃疡性结肠炎治疗作用的研究

目的 探寻黄连水煎液对大鼠溃疡性结肠炎的治疗作用。 方法 大鼠以二甲肼(DMH) 40 mg/kg皮下注射+3%葡聚糖硫酸钠(DSS)水溶液饮用诱导形成大鼠溃疡性结肠炎模型,给予黄连水煎液灌胃治疗5周,观察黄连水煎液对大鼠溃疡性结肠炎的治疗作用。 结果 与模型组相比,黄连水煎液各剂量组能够不同程度改善溃疡性结肠炎引起的大鼠体重增长过慢(P<0.05,P<0.01)。实验第10周各组大鼠结肠均有畸变隐窝灶(ACF)形成, 黄连水煎液各剂量组形成ACF的平均数量明显低于模型组(P<0.01。病理检查结果显示,模型组大鼠可见结肠组织出现了比较严重的不典型增生,腺体排列紊乱,细胞层次明显增多且拥挤,黏液分泌显著减少,黏膜上皮脱落,糜烂重,溃疡多且大,黏膜严重充血、水肿;采用黄连水煎液各剂量组的大鼠上述现象则有所改善,但出现了不同程度的细胞拥挤,核增大和复层。透射电镜结果显示,模型组大鼠出现上皮细胞核染色质聚集,细胞表面微绒毛排列紊乱、断裂现象,黄连水煎液各剂量组的大鼠绒毛排列稀疏,未见断裂。结论 黄连水煎液对大鼠溃疡性结肠炎有显著的治疗作用。     

Radioiodination of balsalazide,bioevaluation, and characterization as a highly selective radiotracer for imaging of ulcerative colitis in mice

This work focuses on tracking ulcerative colitis in mice. High labeling yield and radiochemical purity were achieved for the formation of a [^125/131I]balsalazide radiotracer at optimum conditions of oxidizing agent content (chloramines-T [Ch-T], 75 μg), substrate amount (100 μg), pH of reaction mixture (6), reaction time (30 min), and temperature (37°C), using radioactive iodine-125 (200–450 MBq). The radiolabeled compound, [^125/131I]balsalazide, was stable in serum and saline solution during 24 h. Balsalazide is acting as a peroxisome proliferator-activated receptor (PPARγ). Biodistribution studies were carried in normal and ulcerated colon mice. High uptake of 75 ± 1.90% injected dose/g organ (ID/g) observed in ulcerated mice confirmed the suitability of [¹³¹I]balsalazide as a novel radiotracer for ulcerative colitis imaging in mice.     

实验性溃疡性结肠炎大鼠模型的建立

目的采用三硝基苯磺酸（TNBS）诱导大鼠溃疡性结肠炎动物模型,探讨与人溃疡性结肠炎（UC）的相似程度。方法 TNBS/乙醇法制作溃疡性结肠炎动物模型,分别于造模后1、3、7周3个时间段动态观察模型鼠的一般状态、结肠黏膜大体和病理及电镜变化。同时检测血清肿瘤坏死因子-α（TNF-α）、白细胞介素-2（IL-2）、白细胞介素-4（IL-4）含量。结果大鼠的一般情况、大体病理及组织学病理及电镜变化均与人类溃疡性结肠炎类似,并且血清TNF-α、IL-2、IL-4含量变化亦与人类溃疡性结肠炎的变化基本一致。结论 TNBS可以成功诱导大鼠溃疡性结肠炎动物模型,一般情况、大体与病理表现与人UC的相似度高,有急、慢性转变过程等,而且是免疫学模型,可用于UC免疫学方面的研究。     

Role of nitric oxide synthase inhibitor in experimental colitis induced by 2,4,6-trinitrobenzene sulphonic acid in rats

1. The present study was designed to investigate the role of nitric oxide (NO) in modulating 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. 2. Damage scores and NO synthase (NOS) activity were measured. 3. The damage scores and NOS activity reached a peak on the 4th day after administration of TNBS solution (day 0), thereafter gradually decreasing, and were significantly higher than in the group treated with saline throughout the experimental period. 4. Subsequently, we divided the stage of colitis into two groups, one from day 0 to day 3 after induction of colitis, and the other from day 4 onwards. We evaluated the effects of the NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA), on TNBS-hapten-induced colitis and colonic mucosal blood flow. Two different methods of L-NMMA administration, from day 0 to day 3, and from day 4 onwards, were undertaken. 5. The damage score in the early L-NMMA treatment group was significantly higher than in the group without L-NMMA on day 14. In contrast, the damage score in the late L-NMMA treatment group was not significantly different from the group without L-NMMA. Colonic mucosal blood flow in the early L-NMMA treatment group was not significantly different from that in the late L-NMMA treatment group. 6. These data suggest that NO is important for inhibiting inflammation during the early stages.     

Cellular pathology of experimental colitis induced by trinitrobenzenesulphonic acid (TNBS): Protective effects of recombinant human interleukin-11

The objective of this study was to elucidate colonic mucosal ultrastructural effects of trinitrobenzene-sulphonic acid (TNBS) with and without co-administration of recombinant human interleukin-11 (rhIL-11). Using a standard colitis model (ir alcoholic TNBS), rats were sacrificed at 3~14 days after TNBS. Co-administration of rhIL-11 (100, 300 or 1000 μg/kg sc) was given for protection, and controls received saline or alcohol ir, or rhIL-11 sc alone. Transmission electron microscopy revealed that early TNBS-induced cytopathology was primarily in absorptive cells, changes which occurred prior to goblet cell damage. Progressive cellular changes included vacuolization and increased multivesicular bodies in cell apices, disconfiguration of microvilli, enlarged Golgi apparatuses, enlargement of basal inter-cellular spaces, and eventual desquamation of epithelium and apical bursting. Organelle damage preceded surface changes and resembled ultrastructural changes reported for human ulcerative colitis. The principal effect of rhIL-11 was apparent massive release of mucus from goblet cells, filling the colonic crypts, and suggesting a mode of its protection.     

Influence of simultaneous inhibition of cyclooxygenase-2 and inducible nitric oxide synthase in experimental colitis in rats

The inflamed mucosa in ulcerative colitis produces high amount of prostaglandin (PG) and nitric oxide (NO) through inducible enzymes: cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), respectively, implicating them as potential anti-inflammatory drug targets. COX-2 or iNOS-related treatments in different models of colitis have yielded ambiguous results ranging from exacerbation of disease to abolition of inflammation. iNOS and COX-2 induction is blocked by potent anti-inflammatory glucocorticoids, however, serious side effects including relapses limit their usefulness in colitis for long time. Simultaneous inhibition of iNOS and COX-2 was investigated in the current study in 2, 4, 6 trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Treatment group received rofecoxib, aminoguanidine hydrochloride or their combination at different doses at 48, 36, 24, 12 and 1 h prior to induction of colitis and 12 h later. Colonic myeloperoxidase (MPO), COX-2, nitrate and nitrite, tumor necrosis factor-α (TNF-α) and lipid peroxidation were maximally reduced by combination of 10 mg/kg rofecoxib and 30 mg/kg of aminoguanidine hydrochloride in TNBS-induced colitis in rats. However, maximum increase in SOD and catalase was noted by this combination. Rats treated with rofecoxib, aminoguanidine hydrochloride and their combinations reduced the inflammation, acute colonic damage produced by TNBS as verified by macroscopic changes in colon. Combination of rofecoxib (10 mg/kg) and aminoguanidine hydrochloride (30 mg/kg) has maximal protective effect on colonic injury induced by TNBS enema which is probably, via mechanism of local inhibition of iNOS and COX-2 activity in colonic mucosa and support the idea that simultaneous inhibition of iNOS and COX-2 inhibitors have a promising potential in the treatment of colitis.     

The treatment of ulcerative colitis with balsalazide sodium

Balsalazide sodium (5-aminosalicylic acid [5-ASA] linked to 4-aminobenzyl-β-alanine) was designed to deliver 5-ASA to the colonie mucosa without the sulphapyridine-associated side-effects seen with sulphasalazine. Studies amounting to some 450 patient-years exposure to balsalazide in patients with ulcerative colitis have so far confirmed the expectation of higher efficacy and high patient tolerance of balsalazide.     

青藤碱干预多柔比星肾病大鼠的实验研究

目的:观察白介素-6(IL-6)在多柔比星肾病大鼠肾组织及尿液中的表达及青藤碱(SIN)对其表达的影响.方法:雄性Wistar大鼠120只.随机分为正常组32只,肾病组88只.肾病组大鼠单次尾静脉注射多柔比星5mg/kg,制备微小病变型肾病(MCNS)模型.采用酶联免疫吸附法(ELISA)检测各组大鼠不同时期肾组织及尿...