霉酚酸酯对小鼠肺纤维化的治疗作用-第三军医大学学报.docVIP

霉酚酸酯对小鼠肺纤维化的治疗作用 曹 姝，李少林，兰 曦，王 勇，邹冬玲，臧春宝，王 颖( （400016重庆，重庆医科大学放射医学教研室） [摘要] 目的 探讨霉酚酸酯（ycophenolate mofetil,MMF）A Mycophenolate mofetil alleviates pulmonary fibrosis in mice Cao Shu, Li Shaolin, Lan Xi, Wang Yong, Zou Dongling, Zang Chunbao, Wang Ying (Department of Radiology, College of Preventive Medicine, Chongqing Medical University, Chongqing, 400016,China) [Abstract] Objective To investigate the possible underlying mechanism of mycophenolate mofetil (MMF) in treating bleomycin (BLM)-induced pulmonary fibrosis in mice. Methods Thirty-six C57BL/6 mice were randomly divided into 6 groups (n=6 for each group), including normal control group, MMF control group, BLM model group and MMF treatment groups at low, media and high doses. In 1 d after BLM (6 mg/kg) was intratracheally instilled to the mice from BLM model group and MMF treatment groups, MMF was given orally in the later groups at a dose of 20, 60 and 100 mg/kg respectively once per day for 2 weeks. All mice were killed after the treatment, and their lung tissues were collected. Pulmonary fibrosis was evaluated by Ashcroft score after HE and masson trichrome stainning. The expression of collagen 1 (COLA1) and COLA2 at mRNA levels was determined by RT-PCR. TGF-β1 protein was analyzed by immunohistochemistry. Results BLM-induced pulmonary fibrosis model was successfully constructed. High dose MMF treatment resulted in significant attenuated fibrosis, lower expression of COLA and COLA2 at mRNA level, and decreased TGF-β1 protein (P0.01) when compared with BLM group. No statistic difference was found between the other MMF treatment groups and BLM model groups, MMF control group and normal control group (P0.05). Conclusion MMF significantly attenuates BLM-induce pulmonary fibrosis in mice, which may be due to its inhibition of TGF-β1 expression. [Key words] mycophenolate mofetil; bleomycin; pulmonary fibrosis; TGF-β1; collagen 1 Supported by the Project of Chongqing Sci Tech Committee (CSTC2009BB5059).