茶多酚对博莱霉素导致的小鼠肺纤维化模型的干预作用及其机制  

Effects of Tea Polyphenols on Experimental Pulmonary Fibrosis and Their Mechanisms in Mice

作　　者：曹志飞[1,2] 蒋小岗[1,2,3] 顾振纶[1,2,3] 周文轩[2] 郭次仪[2] 

机构地区：[1]苏州大学医学部,江苏苏州215123 [2]苏州中药研究所,江苏苏州215007 [3]苏州大学衰老与神经疾病实验室,江苏苏州215123

出　　处：《抗感染药学》2011年第3期171-176,共6页Anti-infection Pharmacy

基　　金：香港保健协会资助项目(No.20060903)

摘　　要：目的:研究茶多酚(简称TP)对博莱霉素(bleomycin,BLM)所致肺纤维化动物模型的干预作用,并探讨其作用机制。方法:将昆明种小鼠随机分为假手术组、模型组、醋酸泼尼松组、TP(大、中、小剂量)组。经气管内1次性灌注BLM复制肺纤维化动物模型,造模后第2天起各给药组给予相应药物灌服给药,药物干预后第7,14,28天分别处死动物,观察肺系数、肺组织羟脯氨酸(HYP)、谷胱甘肽(GSH)含质量和总抗氧化能力(T-Aoc)的变化;取固定部位肺组织作病理切片观察其病理形态;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(Col-I)蛋白的表达。结果:TP可显著降低肺纤维化小鼠的肺系数、肺组织中HYP的质量,显著提高肺组织的T-Aoc和GSH质量(P<0.01,P<0.05);光镜观察显示,给予TP干预的小鼠的肺泡炎程度与肺纤维化程度明显减轻(P<0.01,P<0.05);免疫组织化学结果显示TP能显著抑制肺组织中α-SMA、TGF-β1和Col-I蛋白的表达(P<0.01,P<0.05)。结论:TP对博莱霉素所致小鼠肺纤维化具有一定的干预作用,其作用机制可能与下调TGF-β1蛋白的表达和抑制肺肌成纤维细胞的活化以及下调其下游靶基因Col-I蛋白,从而抑制细胞外基质的过度生成以及增加机体的抗氧化能力有关。Objective： To study the effects of tea polyphenols on bleomycin-induced pulmonary fibrosis in mice and to explore their mechanisms. Methods： Mice were randomly divided into 6 groups： control group, model group, prednisolone group and high, moderate and low tea polyphenols groups. The experimental groups were injected intratracheally bleomycin and were further treated with saline, tea polyphenols or prednisone, p.o. daily. The control group was received distilled water.The hydroxyproline（HYp） contents, glutathion（GSH） contents, total antioxidant capacity （T-Aoc） in lung tissue and lung index were assessed at the 7 th, 14 th and 28 th day. Lung samples collected were sliced up, and the changes of structure were measured by light microscope. The expression of transforming growth factor β1 （TGF-β1）, a-smooth muscle actin（α-SMA） and collagen I （Col-I） were analyzed by immunohistochemistry. Results： Tea polyphenols treatment obviously reduced lung index and lung HYP contents in mice with pulmonary fibrosis and significantly improved the T-Aoc and GSH contents in lung tissue（P〈0.01, P〈0.05）. The histological evaluation of lung specimens demonstrated that tea polyphenols dramatically decreased lung inflammation and lung fibrosis（P〈0.01, p〈 0.05）. Tea polyphenols could significantly decrease the expression of protein TGF-β1, α-SMA and Col-I by immonohistostaing technique（P〈0.01, P〈0.05）. Conclusion：Tea polyphenols could alleviate bleomycin-induced pulmonary fibrosis in mice. The mechanisms might be associated with the reinforcement of antioxidant systems.The elevation of the protein expression of TGF-β1 and α-SMA inhibited the proliferation of lung myofibroblast, and then regulation of the protein expression of Col-1 to inhibit the over-express of extracellular matrix.

关 键 词：肺纤维化 茶多酚 博莱霉素 转化生长因子β1(TGF-β1) α-平滑肌肌动蛋白(α-SMA) 

分 类 号：R285.5[医药卫生—中药学]