放射性肺炎方抗大鼠放射性肺纤维化作用机制的研究  

The mechanisms of ARPD in treating radiation-induced lung fibrosis in rats

作　　者：陈不尤[1] 李曙光[1] 肖明兵[3] 江枫[3] 倪温慨[3] 倪润洲[3] 陆亚鹏[4] 黄华[2] 马剑波[1] 仇晓军[1] 

机构地区：[1]江苏省南通大学附属医院放疗科,南通226001 [2]江苏省南通大学附属医院病理科,南通226001 [3]江苏省南通大学附属医院消化研究室科,南通226001 [4]南通大学医学院海洋医学研究所

出　　处：《中华放射医学与防护杂志》2012年第5期475-480,共6页Chinese Journal of Radiological Medicine and Protection

基　　金：基金项目：江苏省南通市社会发展计划（S2008035）

摘　　要：目的探讨放射性肺炎方（ARPD）干预放射性肺纤维化的作用机制。方法将105只雄性SD大鼠采用随机数字表法分为中药（6MVX射线，15Gy单次照射＋ARPD，10ml·kg^-1·d^-1）组、单纯照射组（6MVX射线，15Gy单次照射）和对照组，每组35只，分别于第15、30、60、75、90、105、140天各收集5只大鼠肺组织及血液样本，肺组织行常规病理学检查；Westernblot及RT-PCR法检测转化生长因子．B1（TGF—B1）、纤溶酶原激活物抑制因子-1（PAI-1）、Ⅲ型胶原（collagentype11I，CⅢ）蛋白及基因在组织中的动态表达；ELISA法检测血清TGF-β及血浆PAI-1含量；酸水解法及碱水解法分别检测组织及血清羟脯氨酸（HYP）。结果受照肺组织病理学检查在各时间点均见炎性反应改变，60d后出现纤维化，中药组早期炎性反应、后期纤维化均显著轻于单纯照射组。中药组30d后TGF—β1、PAI-1、CⅢ蛋白及基因在肺组织中表达水平低于同期单纯照射组（蛋白：t=2．49—3．74，t=2．63—4．57，t=2．76—3．83；基因：t=2．59—4．33，t=2．83—4．62，t=2．83～3．96，P〈0．05），15d后血浆PAI-1、血清TGF—B1水平低于同期单纯照射组（t=2．85—6．27，t=3．69—5．27，P〈0．05），60d后肺组织及血清HYP水平低于同期单纯照射组（t=3．65-g．40，t=6．56—3．75，P〈0．05），且肺组织TGF-B1分别与PAI-1及CⅢ的蛋白（r=0．604、0．759，P〈0．05）和基因（r=0．519、0．816，P〈0．05）变化水平呈显著正相关。结论ARPD可通过下调TGF—B1、PAI-1，减少CⅢ的合成干预放射性肺纤维化。Objective To investigate the therapeutic effects and mechanism of anti-radiation pneumonia decoction（ARPD） on radiation induced lung fibrosis in rats. Methods One hundred and five male SD rats in a SPF grade were divided into Chinese medicine group, single radiation group and control group by random digits table method, with 35 in each group. After anesthetization, rats in Chinese medicine and single radiation groups were exposed to 6 MV X-rays at the dose of 15Gy. Rats in Chinese medicine group were treated with ARPD at the dosage of 10 ml·kg^-1 .d^-1 once a day, but rats in single radiation group did not receive ARPD treatment. Rats in control group were treated with neither irradiation nor drugs. Five rats of each group were killed and the lung tissues and blood samples were collected at 15, 30, 60, 75, 90, 105 and 140 d. The pathological changes of lung tissues were observed and the tissue protein and gene expressions of TGF-β1, PAI-1 and collagen type Ⅲ （ C Ⅲ ） were assayed by Western blot and RT-PCR. ELISA was used to detect serum TGF-β1 and plasma PAI-1. Tissue and serum HYP were determined by acid hydrolysis and alkaline hydrolysis methods respectively. Results Inflammation was found in the lung tissues of all the exposed rats. Obvious pathological lung fibrosis was found at 60 d, the inflammation and the fibrosis in treated group were slighter than those in single radiation group. In Chinese medicine group, the protein and gene expression levels of TGF-β1, PAI-1, C HI 30 d（ Protein： t = 2.49 -3.74, t =2.63-4.57 and t =2.76-3.83;Gene： t =2.59-4.33, t =2.83-4.62 and t =2.83- 3.96, P〈0.05）, serumTGF-131 and plasma PAI-1 15 dlater （t =2.85-6.27 and t =3.69-5.27, P 〈0.05）, and the levels of tissue and serum HYP60 dlater （t=3.65-4.40 andt =6.56-3.75, P〈 0. 05）, all of them were lower than those in single radiation groups. There were significant positive correlations between tissue TGF-β1 and PAI-1 as well as C Iii （Protein expression： r = 0. 604,0. 759, P 〈 0. 05;G

关 键 词：放射性肺炎方 放射性肺纤维化 转化生长因子-β1 纤溶酶原激活物抑制因子-1 III型胶原 羟脯氨酸 

分 类 号：R285.5[医药卫生—中药学]