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1、 专硕3班-石群锋-2018ZD026国家自然科学基金申 请 书（2 0 1 8版）资助类别： 面上项目 亚类说明： 附注说明： 项目名称： 补阳还五汤对百草枯诱导肺纤维化中转化生长因子1/Smad3通路的调控机制研究 申 请 人： 石群锋 电 话： 18408257676 依托单位： 成都中医药大学 通讯地址： 成都市十二桥路37号 邮政编码： 610075 单位电话： 61800000 电子邮箱： 申报日期： 2019年03月01日 国家自然科学基金委员会基本信息申请人信息姓名石群锋性别男出生年月19780902民族汉学位硕士职称教授每年工作时间（月） 8电话 18408257676电子
2、邮箱 传真123-3124234国别或地区中国个人通讯地址成都市十二桥路37号 工作单位成都中医药大学 主要研究领域中医药防治呼吸与老年病的研究依托单位信息名称成都中医药大学 联系人XXXX电子邮箱 XXXXXXXX电话XXXXXX网站地址http:/合作研究单位信息单位名称项目基本信息项目名称补阳还五汤对百草枯诱导肺纤维化中转化生长因子1/Smad3通路的调控机制研究英文名称 资助类别面上项目亚类说明附注说明申请代码 H0110：肺间质性疾病H0111：急性肺损伤基地类别研究期限2019年01月2021年12月研究方向：应用基础研究申请经费40.0000万元中文关键词百草枯，肺纤维化，转化生
3、长因子1/Smad3通路英文关键词 Paraquat, pulmonary fibrosis, transforming growth factor beta 1/Smad3 pathway中文摘要百草枯（Paraquat，PQ）化学名为1，1-二甲基4，4-二联吡啶，分子式：CH3（C5H4N）2CH3Cl2，分子量：257.2，自1962年开始作为除草剂被广泛使用。PQ对人畜的急性毒性作用很强，且无有效解毒剂，中毒事件经常发生，病死率居高不下。PQ中毒后肺纤维化过程中，TGF-1/Smad3的表达水平和功能状态会发生改变，亦存在明显的 EndoMT现象，但这些细胞和转导因子与 EndoMT
4、 的相关性及它们在PQ导致肺纤维化过程中的具体生物学机制均尚未明了。PQ致肺纤维化是基于直接毒性作用还是由免疫炎症反应诱导所形成1。祝春青的研究表明已有成熟的注射PQ肺纤维化模型方案，一次性腹腔注射百草枯可制备小鼠肺纤维化模型,40和50 mg/kg为较合适的造模剂量2。补阳换物汤作为活血化瘀的代表方剂，多项研究表明可延缓肺纤维化的进程，并改善肺功能3。本研究拟采用逆转录-聚合酶链反应(RT-PCR) 法检测TGF-1mNA，Smad3 mNA 的表达。同时采用病理切片行HE染色和Masson 染色，光镜下观察病理组织学变化并摄片，参照Szapiel4等方法评价各组大鼠肺组织肺泡炎程度及肺纤维
5、化程度。并设想在以下几方面深入研究：1、扩大样本量，确证其抗炎作用；2、延长观察时间，重点观察后期的抗纤维化作用；3、观察其对成纤维细胞的作用及其机制。国内外目前未见同类报道。参考文献:1 陆远强,姜久昆.转化生长因子1/Smad3通路和百草枯中毒所致上皮-间充质转变J. 中华危重症医学杂志(电子版),2017,10(3):145-148.2祝春青,陈冬波,王喆,等.腹腔注射百草枯构建小鼠肺纤维化模型J.生物技术通讯,2012,23(4):563-566.3杨晗,王飞,王全林,等.补阳还五汤对肺纤维化大鼠肺组织TGF-1/Smad3表达的影响J.中国实验方剂学杂志,2013,19(24):24
6、0-244.4 Szapiel S V，Elson Na，Fulmer J D，et alBleomycin induced interstitial pulmonary disease in the nude，athymic mouseJAm Rev Respir Dis，1979，120: 893. Paraquat (PQ) is chemically known as 1,1-dimethyl 4,4-bipyridine, the molecular formula: CH3 (C5H4N) 2CH3Cl2, molecular weight: 257.2, since 1962 a
7、s a herbicide has been widely used. The acute toxicity of PQ to human and animal is very strong, and there is no effective antidote, poisoning events often occur, the mortality rate is high. In the process of pulmonary fibrosis after PQ intoxication, the expression level and functional status of TGF
8、-beta 1/Smad3 will change, and there is also obvious EndoMT phenomenon. However, the correlation between these cells and transduction factors and EndoMT, and their specific biological mechanism in the process of pulmonary fibrosis induced by PQ are still unclear. PQ induced pulmonary fibrosis is bas
9、ed on direct toxicity or 1 induced by immune inflammatory response. Zhu Chunqings research shows that there is a mature model of pulmonary fibrosis by injection of PQ. Paraquat can be injected intraperitoneally once to establish pulmonary fibrosis model in mice. As a representative prescription of p
10、romoting blood circulation and removing blood stasis, Buyang Changwu Decoction can delay the process of pulmonary fibrosis and improve pulmonary function. In this study, reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of TGF-beta 1 mRNA and Smad3 mRNA. At t
11、he same time, HE staining and Mason staining were used for pathological sections, histopathological changes were observed and photographed under light microscope, and the degree of alveolitis and pulmonary fibrosis in lung tissues of rats in each group were evaluated by Szapiel 4. And envisaged in t
12、he following areas: 1, expand the sample size to confirm its anti-inflammatory effect; 2, prolong the observation time, focusing on the late anti-fibrosis effect; 3, observe its effect on fibroblasts and its mechanism. No similar reports have been reported at home and abroad.Reference:1 Lu Yuanqiang
13、, Jiang Jiukun. Transforming growth factor beta 1/Smads pathway and epithelial-mesenchymal transition induced by paraquat poisoning J.Chinese Journal of Critical Care Medicine (electronic edition), 2017, 10 (3): 145-148.2 Zhu Chunqing, Chen Dongbo, Wang Zhe, et al. Pulmonary fibrosis model of mice was established by intraperitoneal injection of paraquat J.Biotechnology Communication, 2012, 23 (4): 563-566.3 Yang Pi, Wang Fei, Wang Quanlin, et al. Effect of Buyang Huanwu Decoction on the expression of TGF-beta_1/Smad3 in lung tissue of pulmonary fibrosis rats J.Chinese Journal of Experi
