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表没食子儿茶素没食子酸酯对X线照射大鼠肺损伤及TNFα、TGFβ表达和SOD活性的影响
衷敬华1,王勇2,王祥财3,许明君3,施华球3,王钇力3,姜茂竹1,张积仁1*
0
(1.南方医科大学珠江医院肿瘤中心,广州 510282
2.南方医科大学珠江医院药剂科,广州 510282
3.赣南医学院第一附属医院肿瘤科,赣州 341000
*通信作者)
摘要:
目的 观察表没食子儿茶素没食子酸酯(EGCG)对放射线所致大鼠肺损伤的干预作用, 并探讨其可能的作用机制。方法 通过6 MV X射线复制大鼠放射性肺损伤模型, 随机分为模型对照组及大剂量\[200 mg/(kg·d) EGCG\]、中剂量\[100 mg/(kg·d) EGCG\]、小剂量\[50 mg/(kg·d) EGCG\]干预组, 采用H-E及VG染色观察肺组织病理变化和胶原沉积情况,并计算肺泡炎和肺纤维化积分,免疫组织化学(IHC)染色测定肿瘤坏死因子α(TNFα)、转化生长因子β(TGFβ)的表达水平,黄嘌呤氧化酶法测定超氧化物歧化酶(SOD)活性。 结果 40 d时模型对照组大鼠出现明显的肺泡炎和肺纤维化,中、大剂量EGCG干预组大鼠肺泡炎和纤维化积分均低于模型对照组(P<0.01); EGCG小剂量组肺泡炎及肺纤维化积分与模型对照组比较差异无统计学意义。10、20、40 d时,EGCG中、大剂量组肺组织TNFα、TGFβ表达均低于模型对照组及EGCG小剂量组(P<0.01或P<0.05),而SOD活性均高于模型对照组及EGCG小剂量组(P<0.05)。结论 中、大剂量EGCG能减轻放射线所致的肺泡炎和肺纤维化程度,其机制可能与抑制TNFα和TGFβ的表达、提高SOD活性有关。
关键词:  表没食子儿茶素没食子酸酯  放射性肺损伤  肿瘤坏死因子α  转化生长因子β  超氧化物歧化酶
DOI:10.3724/SP.J.1008.2013.00633
投稿时间:2013-03-05修订日期:2013-05-22
基金项目:
Effect of epigallocatechin gallate on TNFα and TGFβ expression, SOD activity and lung injury in rat radiation model
ZHONG Jing-hua1,WANG Yong2,WANG Xiang-cai3,XU Ming-jun3,SHI Hua-qiu3,WANG Yi-li3,JIANG Mao-zhu1,ZHANG Ji-ren1*
(1. Tumor Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, China
2. Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, China
3. Department of Oncology, the First Affiliated Hospital of Gannan Medical College, Ganzhou 341000, Jiangxi, China
*Corresponding author.)
Abstract:
Objective To evaluate the effect of epigallocatechin gallate on radiation-induced lung injury in rats and to discuss the related mechanism. Methods Rat models of radiation-induced lung injury were produced by 6 MV X ray radiation, and then the animals were divided into model control group and low-, medium- and high-dose (200, 100, 50 mg/\[kg·d\]) epigallocatechin gallate groups. The pulmonary histopathological changes and collagen disposition were observed by H-E staining and Van Gieson (VG) staining, and the scores of alveolitis and pulmonary fibrosis were calculated. The expression of tumor necrosis factor-α (TNFα) and transforming growth factor β (TGFβ) in lung tissues was examined by immunohistochemical (IHC) staining. The activity of superoxide dismutase (SOD) was examined by xanthine oxidase method. Results Apparent alveolitis and pulmonary fibrosis were observed in model rats at 40 d after radiation, and the scores of the alveolitis and pulmonary fibrosis were signficantly lower in medium- and high-dose epigallocatechin gallate groups than in the model control group (P<0.01), and there was no difference between the low-dose epigallocatechin gallate group and the model control group. Pulmonary TNFα and TGFβ expression was significantly lower in the medium- and high-dose epigallocatechin gallate groups than in the model control group and low-dose epigallocatechin gallate groups at 10 d, 20 d, and 40 d after radiation (P<0.01 or P<0.05) , while SOD activity in the former two groups were significantly higher compared with those in the model control group and low-dose epigallocatechin gallate groups(P<0.05). Conclusion Medium- and high-dose epigallocatechin gallate can ameliorate the alveolitis and pulmonary fibrosis in radiation-induced lung injury in rats, which might be associated with the inhibition of TNF-α, TGF-β expression and promotion of SOD activity.
Key words:  epigallocatechin gallate  radiation-induced lung injuries  tumor necrosis factor-alpha  transforming growth factor-beta  superoxide dismutase