抑制PARP1活性对博来霉素诱导的肺纤维化的改善作用

doi:10.13481/j.1671-587x.20150302

Abstract

Abstract:

Objective To determine the intervention effect of poly(ADP-ribose) polymerase 1 (PARP1) inhibition on the bleomycin(BML)-induced pulmonary fibrosis in anti-tumor therapies, and to further elucidate the mechanisms of anti-fibrosis role of PARP1 inhibition. Methods Forty eight female ICR mice were randomly divided into normal control (peritoneal injection of saline) and BLM groups (model groups) with doses of 5, 10 and 15 mg·kg^-1, respectively. BLM was peritoneally injected at day 1, 4, 8, 15, 18, 22 and 25. Sixty female ICR mice were randomly divided into normal control, 10 mg·kg^-1 BLM model group, and differeat doses(1, 5 and 10 mg·kg^-1) of PJ34-treated groups. BLM was administrated 20 min after intravenous injection of PARP1 inhibitor PJ34. In all above experiments, 3 mice were sacrificed at day 14, 21 and 28, the lungs were removed for histochemical analysis. HE staining was performed to detect the alveolar damage and Masson staining was performed to detects the collagen deposition. Moreover, A549 cells were exposed to BLM, and the effects of PARP1 inhibition on the expression of EMT biomarkers were detected by Real-time PCR. Results Compared with BLM model group, the alveolar damage and collagen deposition in the lung tissue of the mice in PJ34-treated group were effectively decreased. Compared with BLM group, the E-cadherin mRNA expression levels in A549 cells of the mice in PJ34-treated group was increased (P<0.05), and the expression levels of α-SMA and TGF-β mRNA were decreased(P<0.05 or P<0.01). Conclusion PARP inhibition can affect the expressions of EMT marker genes, and alleviate the BLM-induced pulmonary fibrosis, suggesting PARP1 inhibitors can be utilized to prevent the pulmonary fibrosis in the process of cancer therapy.

Key words: bleomycin, pulmonary fibrosis, poly(ADP-ribose) polymerase 1, epithelial-mesenchymal transition

CLC Number:

R563.9

ZHAO Yan, LIN Tianyu, SUN Ru, HAN Yanlong, MI Donghui, ZENG Xianlu, BA Xueqing. Ameliorative effect of PARP1 inhibition on bleomycin- induced pulmonary fibrosis[J].Journal of Jilin University Medicine Edition, 2015, 41(03): 442-447.

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Ameliorative effect of PARP1 inhibition on bleomycin- induced pulmonary fibrosis

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