INVESTIGATING THE ROLE OF PLUMBAGIN IN ABATING ULCERATIVE COLITIS PATHOGENESIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：建立一种化学诱导的小鼠溃疡性结肠炎模型：为此，我们使用了三组10周龄雌性C57BL/6小鼠，每组包括5个重复。实验1组和实验2组分别给予2%和4%DSS灌胃，连续8天。对照组用正常饲料喂养。每隔一天监测小鼠体重和疾病症状。D-5组体重变化明显，D-8组体重下降4.7%(含2%DSS)，组2(含4%DSS)下降6%以上。第3天出现腹泻等疾病症状。D-3使两组大便稠度变松，D-5加重4%DSS。DSS浓度为4%的第2组，D-8组的直肠出血症状更重。DSS处理的小鼠也表现出挤在一起的疼痛症状。对照组体重略有增加(不到1%)，没有任何疾病症状。DSS小鼠在两组不同的实验中表现出类似的疾病症状，当它们被用作DSS对照白花丹处理时。DSS组小鼠离体肠体积明显缩小。就这样，我们实现了第一个目标。目的：探讨白花蛇舌草素对小鼠UC发病机制的影响：4组小鼠(每组5个重复)同前给予4%DSS。第1组和第2组分别按2 mg/kg体重和4 mg/kg体重给药。第3组：白花黄素(2 mg/kg)+姜黄素(100 mg/kg)。所有小鼠在DSS治疗8天后通过饮水给药。第4组：DSS对照组不给药。白花丹在两个剂量下都显著改善了体重。服用白花丹后，腹泻症状也有所改善。白花丹被发现比单独使用姜黄素更有效，姜黄素是另一种抗炎多酚。离体肠明显大于DSS对照组。希望需要在给药剂量和给药方式上进行各种改变，以明确确定效果。

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.