INVESTIGATING THE ROLE OF PLUMBAGIN IN ABATING ULCERATIVE COLITIS PATHOGENESIS

研究白花丹素在减轻溃疡性结肠炎发病机制中的作用

• 批准号: 8168297
• 负责人: Nilesh Charndra Sharma
• 金额: $ 1.28万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168297
• 关键词: Abate; Anti-Inflammatory Agents; Anti-inflammatory; Body Weight; C57BL/6 Mouse; Computer Retrieval of Information on Scientific Projects Database; Curcumin; Diarrhea; Disease; Dose; Feces; Female; Funding; Goals; Grant; Hemorrhage; Institution; Large Intestine; Modeling; Monitor; Mus; Pain; Pathogenesis; Pharmaceutical Preparations; Research; Research Personnel; Resources; Role; Severities; Source; Symptoms; Testing; Ulcerative Colitis; United States National Institutes of Health; Water; dosage; feeding; improved; plumbagin; polyphenol; rectal; research study

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aim I: To develop a chemically-induced murine-model of ulcerative colitis: Towards this end, we used three groups of 10-week-old female C57BL/6 mice, each group comprising 5 replicates. Experimental groups 1 and 2 were administered 2% and 4% DSS, respectively, via feeding water for 8 days. Control was set up with normal feeding water. Mice body weight and symptoms of disease were monitored every alternate day. Change in body weight was noticeable by D-5, and by D-8, a decrease of 4.7% in group 1 (with 2% DSS) and more than 6% in group 2 (4% DSS) was recorded. Disease symptom such as diarrhea was manifest by 3rd day. While consistency of stool became loose by D-3 in both groups, 4% DSS caused more severity by D-5. Likewise, symptom of rectal bleeding was more severe by D-8 in group 2 with 4% DSS. DSS-treated mice also presented symptoms of pain by huddling. Control registered negligible increase (less than 1%) in body weight with no disease symptoms. DSS mice presented similar disease symptoms in two different sets of experiments when they were used as DSS-control against plumbagin treatments. Size of isolated large intestine was found significantly reduced in DSS mice. In this way, we achieved the first goal. Aim II: To test the effects of plumbagin on UC pathogenesis in murine model: Four groups of mice (each having 5 replicates) were administered 4% DSS as before. Group 1 and group 2 were treated with plumbagin at the rate of 2mg/kg body weight and 4mg/kg body weight, respectively. Group 3 was treated with plumbagin (2mg/kg) and curcumin (100mg/kg). Drugs were administered via feeding water after 8 days of DSS treatment to all mice. Group 4: DSS-control was given no drug. Plumbagin improved body weight significantly at both doses. Symptoms of diarrhea also improved with plumbagin. Plumbagin was found to be more effective singly than in combination with curcumin, another anti-inflammatory polyphenol. Isolated large intestine was significantly larger than DSS- control. It is hoped that various alterations in the dosage and mode of drug administration will be required to determine the effect clearly.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目标一：为了开发溃疡性结肠炎的化学诱导的鼠模型：为此，我们使用三组10周龄雌性C57 BL/6小鼠，每组包括5个重复。实验1组和实验2组分别以2%和4%的DSS喂饲8天。对照组用正常的饲养水。每隔一天监测小鼠体重和疾病症状。到D-5时体重变化明显，到D-8时，第1组（含2% DSS）和第2组（含4% DSS）分别记录到体重下降4.7%和6%以上。第3天出现腹泻等疾病症状。虽然两组中的粪便稠度在D-3时变得松散，但4%DSS在D-5时引起更严重的程度。同样，第2组（4%DSS）的直肠出血症状在D-8时更严重。DSS处理的小鼠也通过蜷缩呈现疼痛症状。对照组的体重增加可忽略不计（小于1%），无疾病症状。当DSS小鼠用作对抗白花丹素处理的DSS对照时，它们在两组不同的实验中表现出相似的疾病症状。发现DSS小鼠的离体大肠尺寸显著减小。这样，我们实现了第一个目标。目标二：为了在鼠模型中测试白花丹素对UC发病机理的影响：如前所述向四组小鼠（每组具有5个重复）施用4%DSS。第1组和第2组分别以2 mg/kg体重和4 mg/kg体重的剂量给予白花丹素。第3组：白花丹素（2 mg/kg）和姜黄素（100 mg/kg）灌胃。在DSS处理8天后，通过给所有小鼠喂水来施用药物。第4组：DSS对照组不给药。白花丹素在两种剂量下均显著改善体重。服用白花丹素后腹泻症状也得到改善。研究发现，白花丹素单独使用比与另一种抗炎多酚姜黄素联合使用更有效。离体大肠显著大于DSS-对照。希望需要对给药剂量和方式进行各种改变，以明确确定其效果。