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表没食子儿茶素没食子酸酯对博莱霉素致小鼠肺纤维化的干预作用及其机制探讨
引用本文:曹志飞,蒋小岗,张洪涛,顾振纶,周文轩,郭次仪.表没食子儿茶素没食子酸酯对博莱霉素致小鼠肺纤维化的干预作用及其机制探讨[J].苏州大学学报(自然科学版),2010,30(2):265-268,I0001.
作者姓名:曹志飞  蒋小岗  张洪涛  顾振纶  周文轩  郭次仪
作者单位:曹志飞,CAO Zhi-fei(苏州大学医学部,江苏苏州215123;苏州中药研究所,江苏苏州215007);蒋小岗,顾振纶,JIANG Xiao-gang,GU Zhen-lun(苏州大学医学部,江苏苏州215123;苏州中药研究所,江苏苏州215007;苏州大学衰老与神经疾病实验室,江苏苏州215123);张洪涛,ZHANG Hong-tao(苏州大学医学部,江苏苏州,215123);周文轩,郭次仪,ZHOU Wen-xuan,GUO Ci-yi(苏州中药研究所,江苏苏州,215007)
基金项目:香港保健协会研究项目,江苏省中医药局资助项目,苏州市2008年度科技发展计划(国际科技合作)项目
摘    要:目的探讨表没食子儿茶素没食子酸酯(EGCG)对博莱霉素(BLM)所致小鼠肺纤维化的干预作用及其相关机制。方法 32只昆明种小鼠随机分为假手术组、模型组、EGCG治疗组和醋酸泼尼松阳性对照组,每组8只。采用气管内注射博莱霉素复制小鼠肺纤维化模型。造模后,治疗组分别灌服相应的受试药物,假手术组和模型组灌服等量的生理盐水。28d后观察肺组织肺系数、羟脯氨酸(HYP)含量、丙二醛(MDA)和谷胱甘肽(GSH)含量的变化;取固定部位肺组织做病理组织学检查;免疫组织化学技术测定肺组织中α平滑肌肌动蛋白(α-SMA)、转化生长因子-β1(TGF-β1)和I型胶原(ColⅠ)蛋白的表达。结果给药治疗28d后,EGCG能明显降低肺系数(P〈0.01)、肺组织HYP含量(P〈0.01)和MDA含量(P〈0.05),明显升高肺组织中GSH含量(P〈0.01);病理组织学检查结果显示,EGCG组肺组织肺泡炎程度和肺组织纤维化程度明显减轻(P〈0.01,P〈0.05);EGCG能明显抑制肺组织中α-SMA、TGF-β1和ColⅠ蛋白的表达(P〈0.01)。结论 EGCG对博莱霉素所致小鼠肺纤维化具有一定的干预作用,其机制可能与抗氧化作用和降低TGF-β1蛋白的表达进而抑制肺肌成纤维细胞的活化有关。

关 键 词:表没食子儿茶素没食子酸酯  肺纤维化  博莱霉素  羟脯氨酸  小鼠

Effects and Mechanisms of Epigallocatechin Gakkate (EGCG) on Bleomycin-induced Pulmonary Fibrosis in Mice
CAO Zhi-fei,JIANG Xiao-gang,ZHANG Hong-tao,GU Zhen-lun,ZHOU Wen-xuan,GUO Ci-yi.Effects and Mechanisms of Epigallocatechin Gakkate (EGCG) on Bleomycin-induced Pulmonary Fibrosis in Mice[J].Suzhou University Journal of Medical Science,2010,30(2):265-268,I0001.
Authors:CAO Zhi-fei  JIANG Xiao-gang  ZHANG Hong-tao  GU Zhen-lun  ZHOU Wen-xuan  GUO Ci-yi
Affiliation:1.Medical College,Soochow University,Jiangsu Suzhou 215123,China;2.Suzhou Institute of Chinese Materia Medica,Jiangsu Suzhou 215007,China;3.Laboratory of Aging and Nervous Diseases,Soochow Univer-sity,Jiangsu Suzhou 215123,China)
Abstract:Objective To study the effects and mechanisms of EGCG on bleomycin-induced pulmonary fibrosis in mice.Methods Kunming mice were randomly divided into control group and three experimental groups(BLM group,BLM-EGCG group and BLM-prednisone group).The experimental groups were injected intratracheally with BLM and were further treated with saline,EGCG or prednisone,p.o.daily.The animals in the control group was received distilled water.The HYP contents,MDA contents and GSH contents in lung tissue and the lung index were assessed at the 28th day.Lung samples collected were stained with hematoxylin-eosin (HE) staining and scored.The expression of α-smooth muscle actin (α-SMA),transforming growth factorβ1 (TGF-β1) and collagen I (Col Ⅰ) were analyzed by immunohistochemistry.Results Compared with model group,EGCG treatment dramatically reduced the lung index,HYP contents and MDA contents in lung tissue (P0.01,P0.05),significantly improved the GSH contents in lung tissue (P0.01).Lung histology in the EGCG-treated mice was also ameliordied (P0.01,P0.05).Moreover,EGCG could significantly decrease the expression of protein α-SMA,TGF-β1 and Col Ⅰ(P0.01).Conclusion EGCG could alleviate BLM-induced pulmonary fibrosis in mice,probably by the reinforcement of antioxidant systems,decreasing the expression of TGF-β1 protein and then inhibiting the proliferation of lung myofibroblast.
Keywords:epigallocatechin gallate  pulmonary fibrosis  bleomycin  hydroxyproline  mice
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