below是什么意思分类号：R9 单位代码：10752 密级：公开学号：2009039
宁夏医科大学
硕士研究生学位论文
苦参碱调控p16INK4a/cyclinD1/CDK4通路干预N-丁基-N-(4-羟丁基)亚硝基胺致大鼠辅音字母
膀胱癌的研究
Matrine suppress tumor invasion in N-butyl-N-(4-hydroxybutyl) nitrosamine-induced urinary bladder cancer via regulation of
p16INK4a/cyclinD1/CDK4 pathway
学位申请人：国亚芳
指导教师：戴贵东教授
申请学位门类级别：医学イモウトノカタチ
专业名称：药理学
研究方向：肿瘤药理
所在学院：药学院
论文完成日期：二〇一二年四月
宁夏医科大学研究生院
Ningxia Medical University
Thesis for Application of Master’s Degree
Matrine suppress tumor invasion in N-butyl-N-(4-hydroxybutyl) nitrosamine-induced urinary bladder cancer via regulation of
p16INK4a/cyclinD1/CDK4 pathway
英译汉翻译
Student’s Name: Guo Yafang
Supervisor：Dai Guidong
Subject Category: Medical Science
Major: Pharmacology
spillSpecialty: Oncopharmacology
School: Ningxia Medical University
Completion Date: Apr.2012
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苦参碱调控p16INK4a/cyclinD1/CDK4通路干预
N-丁基-N-(4-羟丁基)亚硝基胺致大鼠膀胱癌的研究
摘要
目的研究苦参碱对N-丁基-N-(4-羟丁基)亚硝胺(BBN)诱导的大鼠膀胱癌膀胱组织p16INK4a/cyclinD1/CDK4细胞周期调控通路中各蛋白的表达，阐明苦参碱降低大鼠膀胱癌浸润率的分子机制。
方法雄性Sprague-Dawley大鼠，随机分为6组，分别是正常组、模型组、塞来昔布阳性药物对照组、苦参碱50、100和200mg·kg-1·d-1剂量组。塞来昔布按500mg·kg-1·d-1 灌胃给药；苦参碱剂量分别为50、100、200mg·kg-1·d-1灌胃给药；正常对照组和模型组给予等剂量生理盐水。在上述给药的基础上，从第二周开始除正常组给予等体积溶剂对照液外，其余各组灌胃给予膀胱癌致癌剂BBN（200mg·0.5mL-1·只-1），每周2次，共给药8周。各组动物于35周后处死，组织病理学检查膀胱组织形态以及免疫组织化学方法检测膀胱组织中p16INK4a的表达情况；Western blot方法测定各组大鼠膀胱组织p16INK4a/cyclinD1/CDK4细胞周期调控通路中p16INK4a、cyclinD1、CDK4的表达情况。
结果免疫组织化学结果显示p16INK4a蛋白表达定位于胞核，少量表达于胞浆。Western blot结果显示，与正常组相比，BBN诱导的大鼠膀胱癌模型组膀胱组织中p16INK4a 的表达量显著性降低（P＜0.01），cyclinD1和CDK4的表达明显升高（P＜0.01）；与BBN 诱导的大鼠膀胱癌模型组相比，苦参碱200mg·kg-1·d-1剂量组p16INK4a的表达量显著升高（P＜0.05），苦参碱50和200mg·kg-1·d-1剂量组cyclinD1的表达量下降（P＜0.05），CDK4蛋白在苦参碱200mg·kg-1·d-1剂量组也表现为显著性降低（P＜0.05）。状语从句
结论苦参碱能通过对大鼠膀胱组织p16INK4a/cyclinD1/CDK4细胞周期调控通路的影响，进而抑制BBN诱导的大鼠膀胱癌的发展。
关键词苦参碱，BBN，膀胱癌，发展，p16INK4a，cyclinD1，CDK
Matrine suppress tumor invasion in N-butyl-N-(4-hydroxybutyl) nitrosamine-induced urinary bladder cancer via regulation of
p16INK4a/cyclinD1/CDK4 pathway
ABSTRACT
Objectives This study was designed to explore the effect and molecular mechanism of matrine on N-buthy1-N-(4-hydroxybuty1) nitrosamine(BBN)-induced bladder cancer in rats, the pathway of p16INK4a/cyclinD1/cdk4 were investigated.
Methods Male Sprague-Dawley rats were randomly divided into six groups, the control, BBN, celecoxib, matrine (50, 100 and 200 mg·kg-1·d-1) group. The bladder cancer was induced by daily intragastric administration of N-bthyl-N-(4-hydroxybutyl) nitrosamine (BBN) (200mg·0.5ml-1) twice a week for eight weeks in Sprague-Dawley rats. One week before administration of BBN, rats were given celecoxib(500mg·kg-1·d-1) and different do (50, 100 and 200mg·kg-1·d-1) of matrine or saline by intragastric, whereas the group were only fed with saline from the beginning. Animals were sacrificed at the end of 35th week, immunohistochemical method was ud to detect the expression of p16INK4a, and the protein content of p16INK4a/cyclinD1/CDK4 pathway in bladder tissue were m
四级考试时间几点到几点easured by the method of Western blot.
Results Compared with control group, the protein level of p16INK4a was significantly reduced in BBN-induced bladder cancer model group(P＜0.01), while the expression of cyclinD1 and CDK4 were showed markedly increa(P＜0.01). Matrine (200mg·kg-1·d-1) treatment could increa the expression of p16INK4a compared with BBN group (P＜0.05). Compared with BBN group, Matrine (50 and 200mg·kg-1·d-1) treatment groups could reduce
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