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

doi:10.3877/cma.j.issn.1674-6902.2017.03.006

Abstract

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

feng Liu, huaping Huang, mingjing Chen. Insulin-like growth factor-1 promotes pulmonary fibrosis with time in acute lung injury induced by oleic acid in a rat model[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2017, 10(03): 271-276.

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References 20

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状态时段	d0	d1	d3	d7	d14	d21	d28
肺泡炎(分)	0.00±0.00	1.00±0.00	2.33±0.58	2.00±0.00	1.67±0.58	1.33±0.57	1.00±0.00
肺纤维化(%)	0.00±0.00	0.00±0.00	3.33±5.77	20.00±0.00	23.33±5.77	36.67±5.77	41.67±2.87

状态时段	d0	d1	d3	d7	d14	d21	d28
肺泡炎(分)	0.00±0.00	1.00±0.00	2.33±0.58	2.00±0.00	1.67±0.58	1.33±0.57	1.00±0.00
肺纤维化(%)	0.00±0.00	0.00±0.00	3.33±5.77	20.00±0.00	23.33±5.77	36.67±5.77	41.67±2.87

时相点		d0	d1	d3	d7	d14	d21	d28
IGF-1mRNA		?	?	?	?	?	?	?
?	油酸组	2.15±0.13	2.20±0.04	2.44±0.10^a	2.89±0.08^b	2.94±0.10^b	3.68±0.16^b	3.32±0.05^b
?	对照组	2.18±0.19	2.17±0.12	2.12±0.10	2.19±0.05	2.21±0.04	2.15±0.06	2.11±0.16
IGF-1R mRNA		?	?	?	?	?	?	?
?	油酸组	2.28±0.13	2.33±0.40	2.52±0.17^a	3.02±0.09^b	3.08±0.09^b	3.81±0.18^b	3.46±0.04^b
?	对照组	2.26±0.18	2.25±0.11	2.19±0.12	2.25±0.05	2.28±0.05	2.21±0.05	2.19±0.15

时相点		d0	d1	d3	d7	d14	d21	d28
IGF-1mRNA		?	?	?	?	?	?	?
?	油酸组	2.15±0.13	2.20±0.04	2.44±0.10^a	2.89±0.08^b	2.94±0.10^b	3.68±0.16^b	3.32±0.05^b
?	对照组	2.18±0.19	2.17±0.12	2.12±0.10	2.19±0.05	2.21±0.04	2.15±0.06	2.11±0.16
IGF-1R mRNA		?	?	?	?	?	?	?
?	油酸组	2.28±0.13	2.33±0.40	2.52±0.17^a	3.02±0.09^b	3.08±0.09^b	3.81±0.18^b	3.46±0.04^b
?	对照组	2.26±0.18	2.25±0.11	2.19±0.12	2.25±0.05	2.28±0.05	2.21±0.05	2.19±0.15

时相点		d0	d1	d3	d7	d14	d21	d28
IGF-1蛋白		?	?	?	?	?	?	?
?	油酸组	134.33±9.50	142.33±8.50	164.33±8.02^a	202.00±10.82^b	214.33±6.03^b	276.33±10.21^b	259.33±10.60^b
?	对照组	132.67±7.02	131.33±9.07	134.00±8.72	133.33±4.51	136.00±7.00	134.33±7.51	134.00±9.85
IGF-1R蛋白		?	?	?	?	?	?	?
?	油酸组	153.33±7.57	163.00±8.54	183.67±10.50^a	223.00±9.54^b	235.00±6.56^b	297.67±10.02^b	279.67±11.68^b
?	对照组	157.00±10.54	150.67±9.07	154.67±5.69	156.00±10.54	154.00±8.00	154.00±5.57	155.00±9.54

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