清燥救肺汤对乌拉坦诱导肺癌模型鼠TGF-β1、Smad2和p38 MAPK的影响  

Effect of Qingzao Jiufei Tang on TGF-β1,Smad2 and p38MAPK in mice with lung Cancer induced by urethane

作　　者：熊秋迎[1] 朱金华[2] 孙昊鑫[2] 郭慧君[2] 胡丽霞[2] 叶荷平[2] Xiong Qiuying;Zhu Jinhua;Sun Haoxin;Guo Huijun;Hu Lixia;Ye Heping(Department of Pathology,the First Affiliated Hospital of Nanehang University,Nanchang 330006;Jiangxi University of Traditional Chinese Medicine,Nanehang 330004)

机构地区：[1]南昌大学第一附属医院病理科,南昌330006 [2]江西中医药大学,南昌330004

出　　处：《中药药理与临床》2018年第3期14-18,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：2016年江西省卫生计生委中医药科技计划项目(NO.2016A031)

摘　　要：目的:研究清燥救肺汤对乌拉坦诱导肺癌模型鼠TGF-β1、Smad2和p38 MAPK的影响。方法:选择清洁级KM小鼠,随机分为6组,即正常组、模型组、六味地黄丸4.6g/kg组、清燥救肺汤33.6g/kg、16.8g/kg、8.4g/kg组。除正常组外,其余各组小鼠腹腔注射乌拉坦800mg/kg,每周两次,连续五周,复制小鼠肺癌模型。给药与造模同时进行,1次/d,连续15周。清燥救肺汤33.6g/kg、16.8g/kg、8.4g/kg组、六味地黄丸4.6g/kg组分别给予等体积药物,正常组与模型组灌胃生理盐水。15周后,取肺脏检测。肉眼及镜下计数双肺小鼠肺肿瘤结节数,并计算小鼠肺肿瘤发生率;Western Blot测定肺组织TGF-β1、Smad2和p38 MAPK蛋白的表达;免疫组化检测肺组织TGF-β1、Smad2和p38 MAPK活性的表达。结果:清燥救肺汤(8.4、16.8、33.6g/kg)均能使肺肿瘤发生率从91.7%降至58.3~75.0%,平均肿瘤结节数从5降至3,明显降低肺癌模型鼠肺组织TGF-β1、Smad2和p38 MAPK蛋白的表达,并可使肺组织中TGF-β1、Smad2和p38 MAPK活性的表达也显著下降。结论:清燥救肺汤可能通过抑制TGF-β1、Smad2和p38 MAPK的过度表达,从而多靶点调控TGF-β1/Smad2及p38 MAPK等信号通路来实现延缓肺癌的发生发展及转移。Objective： To study the effect of Qingzao Jiufei Tang（QJT） on TGF-β1,Smad2 and p38 MAPK in mice with lung Cancer induced by urethane. Methods： KM mice were randomized into six groups： the control group（A）,the model group（B）,Liuwei Dihuang Wan（4. 6 g/kg）group（C） and QJT（33. 6 g/kg） group（D）,QJT（16. 8 g/kg） group（E）,QJT（8. 4 g/kg） group（F）. Except A,lung cancer was induced by subcutaneous injection of 0. 8 g/kg urethane in the other groups,twice one week,which lasted for five weeks. Administration of drug and establishing model at the same time,once a day,lasted for fifteen weeks. Mice in C,D,E,F groups were respectively given Liuwei Dihuang Wan（4. 6 g/kg） and QJT（33. 6,16. 8,8. 4 g/kg）,those in A,B were given saline. After fifteen weeks＇ administration,mice were sacrificed,lung tissues were tested. Expressions of TGF-β1,Smad2 and p38 MAPK proteins in lung tissues were detected by Western Blot method. Activity expressions of TGF-β1,Smad2 and p38 MAPK in lung tissues were determined by immunohistochemical method. Results： In the process of lung carcinogenesis,QJT（8. 4,16. 8,33. 6 g/kg） significantly reduced lung chemical carcinogenesis（dropped from 91. 7% to 58. 3 ~ 75.0%） and tumor nodules（dropped from 5 to 3） in mice（P〈0. 05）. QJT significantly decreased expressions of TGF-β1,Smad2 and p38 MAPK proteins（P〈0. 05 or P〈0. 01） and the activity expressions of TGF-β1,Smad2 and p38 MAPK（P〈0. 05 or P〈0. 01） in lung tissues of mice with lung Cancer. Conclusions： QJT could decrease overexpressions of TGF-β1,Smad2 and p38 MAPK,thus regulate the signaling pathways of TGF-β1/Smad2 and p38 MAPK by multiple targets,in order to delay the development and metastasis of the lung cancer.

关 键 词：清燥救肺汤 肺癌 转化生长因子β1 SMAD2 P38丝裂原活化蛋白激酶 

分 类 号：R285.5[医药卫生—中药学]