On The Blog. Iloilo Prostaglandin Bleomycin Induced Pulmonary Fibrosis In Mice, Rats And Relevant Mechanisms,

Objective●To investigate the interventional effectiveness of Iloprost on Bleomycin-induced pulmonary fibrosis in mice.●To further explore the mechanisms of the preventive role of Iloprost on bleomycin-induced pulmonary fibrosis in mice.Method●The BPF model was established by a single dosage of 2mg/kg bleomycin intra-tracheal injection.Single dosage of 200ug/kg Iloprost intraperitoneal injection was given to the mice.●The effectiveness was evaluated by the weight curve and survival rate. The fibrosis degree was determined biochemically by hydroxyproline assay in lung tissue,Ashcroft' scoring pathologically by using HE and Masson Trichrome stained lung tissue,alveolar septal thickening measurement and physical index.●The expression of the cytokines and chemokines in lung tissue was assayed by semi-quantitative RT-PCR.●ELISA kits was used to evaluate the cytokines and chemokines in BALF at protein level.Result●Compare to the mice administrated by bleomycin,there was significant protection in BPF mice treated with iloprost in several aspects:weight (p＜0.05),survival rate(90%vs 40%,p＜0.01),hydroxyproline content (56.04±2.23 ug/ml vs 77±6.01ug/ml,p＜0.05),Ashcroft' scoring (3.35±0.54 vs 5.64±0.18,p＜0.01),alveolar septal thickening (23.03±4.91 vs 56.12±4.06,p＜0.01),compliance(0.02015±0.00074 ml/cmH2O vs 0.01448±0.00178ml/cmH2O,p＜0.05) and elastance (49.96±1.83 cmH2O/ml vs 86.84±13.13cmH2O/ml,p＜0.01) of the lung tissue.●The mRNA expression of the cytokines tested,IL-6(0.75±0.33 vs 1.67±0.22,p＜0.05),TNF-α(0.28±0.02 vs 0.44±0.05,p＜0.05),TGF-β(0.90±0.10 vs 1.26±0.07,p＜0.05) was significantly down-regulated in the lung tissues from mice treated with iloprost.The expression of IFN-y (0.90±0.10 vs 1.26±0.07,p＜0.05),CXCL10(1.03±0.09 vs 0.76±0.03, p＜0.05),CXCL11(0.35±0.04 vs 0.22±0.02,p＜0.05) was significantly up-regulated.●The up-regulated expression of IFN-γ(59.25±10.49 vs 18.91±9.84 pg/ml,p＜0.05),CXCL10(108.4±5.46 vs 65.88±6.39 pg/ml,p＜0.01) and down-regulated expression of IL-6(26.5±4.04 vs 131.5±38.21 pg/ml,p＜0.05),TGF-β(1906±988 vs 14350±4798pg/ml,p＜0.01) was found in BALF from mice treated with iloprost.Conclusion●The mortality and pulmonary fibrosis degree were significantly reduced by the intrapedtoneal injection of Iloprost.●The inhibition of inflammatory cytokines expression was the potential mechanism that iloprost protected from bleomycin-induced pulmonary fibrosis in mice.●The induction of anti-angiogenesis mediators associated with upregulation of IFN-γ,including CXCL10 and CXCL11,was another potential protective mechanism of iloprost.