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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 目标 I：开发化学诱导的溃疡性结肠炎小鼠模型：为此，我们使用了三组 10 周龄雌性 C57BL/6 小鼠，每组包含 5 个重复。实验组1和2分别通过喂水施用2%和4% DSS，持续8天。用正常饲喂水进行对照。每隔一天监测小鼠体重和疾病症状。第 5 天体重变化明显，第 8 天体重变化明显，第 1 组（2% DSS）体重下降 4.7%，第 2 组（4% DSS）体重下降超过 6%。第3天出现腹泻等疾病症状。虽然两组粪便的稠度在 D-3 时都变得稀松，但 4% DSS 在 D-5 时导致更严重。同样，在 4% DSS 的第 2 组中，D-8 时直肠出血的症状更为严重。接受 DSS 治疗的小鼠也表现出蜷缩的疼痛症状。对照体重增加可忽略不计（小于 1%），且无疾病症状。当 DSS 小鼠被用作白花丹素治疗的 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 小鼠离体大肠的大小显着减小。这样，我们就达到了第一个目标。目的 II：在小鼠模型中测试白花丹素对 UC 发病机制的影响：四组小鼠（每组 5 个重复）如前所述给予 4% DSS。第1组和第2组分别以2mg/kg体重和4mg/kg体重的剂量用白花丹素治疗。第3组用白花丹素(2mg/kg)和姜黄素(100mg/kg)治疗。对所有小鼠进行 DSS 治疗 8 天后，通过喂水给药。第 4 组：DSS 对照不给予任何药物。两种剂量的白花丹素均显着改善体重。白花丹素还可以改善腹泻症状。研究发现，单独使用白花丹素比与另一种抗炎多酚姜黄素联合使用更有效。离体大肠明显大于DSS对照。希望需要对剂量和给药方式进行各种改变才能清楚地确定效果。