Insulin-like growth factor-1 promotes pulmonary fibrosis with time in acute lung injury induced by oleic acid in a rat model

Abstract

Objective To investigate the role of insulin-like growth factor-1 in the development of pulmonary fibrosis in acute lung injury induced by oleic acid in a rat model. Methods The mice were injected with oleic acid (0.3 ml/kg) intravenously to induce ALI. Sixty BALB/c mice were randomly divided into an oleic acid group (n=35) and a control group (n=25). The oleic acid group was treated with oleic acid (0.3 ml/kg) intravenously and the control group was treated with same amount of normal saline. 3 rats in each group respectively were sacrificed on 1st, 3rd, 7 th, 14 th, 21 th and 28 th day after the treatment. The expression levels of IGF-1 and IGF-1R mRNA were detected by quantitative real-time polymerase chain reaction ( qRT-PCR), the protein levels of IGF-1 and IGF-1R were measure by western blotting assay and the number of positive cells of IGF-1, IGF-1R, collagen Ⅰ, collagenⅢ, α-smooth muscle actin, CD68 and proliferating cell nuclear antigen were measure by immunohistochemical assay, meanwhile, pathological changes were observed in sections of left lung stained with Hematoxylin Eosin and Masson. Results Compared with control group, the expression levels of IGF-1 and IGF-1R mRNA, the protein levels and the number of positive cells of IGF-1 and IGF-1R in lung homogenate of the rats in the oleic acid group were significantly increased with time(P<0. 05). And the number of positive cells of IGF-1, IGF-1R collagen Ⅰ, collagenⅢ, α-smooth muscle actin, CD68 and proliferating cell nuclear antigen synchronously increased with time in the oleic acid group. The phase in early (1-3 d) was characterized by acute alveolitis. The phase in later stage (7-21 d) was characterized by marked proliferation of fibrous tissue. It would become slower after 28 th day. Conclusions The expression of IGF-1, IGF-1R, collagen Ⅰ, collagenⅢ, α-smooth muscle actin, CD68 and proliferating cell nuclear antigen are increased strong with time in lung homogenate in acute lung injury induced by oleic acid in a rat model which are consistent with the progression of pulmonary fibrosis in the comparison of the lung histopathological examination. The study indicated that insulin-like growth factor-1 probably promoted pulmonary fibrosis by up-regulating the expression of collagen Ⅰ, collagenⅢ, α-smooth muscle actin, CD68 and proliferating cell nuclear antigen which could increase pulmonary interstitial collagen deposition and proliferation of myofibroblasts in acute lung injury induced by oleic acid in a rat model. Key words: Oleic acid; Acute lung injury; Pulmonary fibrosis; Insulin-like growth factor-1; Insulin-like growth factor-1 receptor