srt1720, a sirt1 activator, aggravates bleomycin-induced lung injury in micesrt1720 sirt1激活器,加剧bleomycin-induced在小鼠肺损伤.pdf

Food and Nutrition Sciences, 2012, 3, 157-163 /10.4236/fns.2012.32024 Published Online February 2012 (http://www.SciRP.org/journal/fns) SRT1720, a SIRT1 Activator, Aggravates Bleomycin-Induced Lung Injury in Mice 1 1 1 1 2 Shingo Imanishi , Ryuji Hayashi , Tomomi Ichikawa , Kensuke Suzuki , Masakiyo Sasahara , Takashi Kondo3 1 1 , Hirofumi Ogawa , Kazuyuki Tobe 1First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 2 Japan; Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; 3Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. Email: htaro@med.u-toyama.ac.jp Received October 12th, 2011; revised November 29th, 2011; accepted December 6th, 2011 ABSTRACT Diagnosis and management of interstitial lung diseases (ILDs), caused by lung epithelial injury followed by apoptosis, are often challenging. It has been controversial whether the SIRT1 protein, a principal modulator of longevity due to caloric restriction, ameliorates or aggravates ILD in animal models. Here we examined the effect of SRT1720, a syn- thetic activator of SIRT1, on bleomycin-induced lung injury in a mouse model and apoptosis in cultured epithelial cells. Oral intubation of SRT1720 over a period of 15 days caused body weight loss and a high mortality rate among bleomy- cin-treated mice. Histological examinations showed that the SRT1720 load increased fibrosis in the bleomycin-treated lung. An analysis of bronchoalveolar lavage fluid revealed remarkably increased numbers of inflammatory cells in the SRT1720-treated group. Moreover, the apoptosis of A549 lung cancer