Effects Of Indole-3-carbinol On Bleomycin-induced Pulmonary Fibrosis In Mice/rats And Its Mechanisms

Objective: To investigate the effects and mechanisms of indole-3-carbinol （I3C） onbleomycin-induced pulmonary fibrosis in mice and rats.Methods: The ICR mice were divided into six groups randomly：control group, modelgroup, prednisolone group(6.67mg·kg^-1) and I3C low-dose (25mg·kg^-1), middle-dose (50mg·kg^-1), high-dose group (100mg·kg^-1). The SD rats were divided into six groupsrandomly：control group, model group, prednisolone group (3.34mg·kg^-1) and I3Clow-dose (12.5mg·kg^-1), middle-dose (25mg·kg^-1), high-dose group (50mg·kg^-1).Pulmonary fibrosis model was replicated by single intratracheal injection of bleomycin. Inthe next day, the animals were treated by intragastric administration once a day. After28days, the animals were sacrificed. The lung index and the levels of T-AOC and HYP weremeasured, and the pathologic changes of the lung tissue were obtained by HE and Massonstaining. The levels of IL-1β and IL-6in bronchoalveolar lavage fluid were assayed byELISA. The levels of α-SMA, Collagen I, TGF-β1, Smad2and Smad7mRNA wereassayed by RT-PCR. The levels of miRNA-21and Let-7d were assayed by Real TimeRT-PCR. The levels of α-SMA, Vimentin, Caveolin-1, TGF-β1and Smad2protein wereanalyzed by western blot.Results: I3C improved the activity of T-AOC in serum, and reduced pulmonary indexand the content of HYP as well（P<0.05or P<0.01）; the alveolitis and fibrosis extent wereattenuated significantly（P<0.05or P<0.01）; the levels of IL-1β and IL-6inbronchoalveolar lavage fluid were decreased significantly; the levels of TGF-β1, Smad2,Vimentin, α-SMA and Collagen I were all decreased significantly（P<0.05or P<0.01）;thelevels of Caveolin-1and Smad7were all increased significantly（P<0.05or P<0.01）; thelevel of miRNA-21was decreased significantly, while the level of Let-7d was increasedremarkably（P<0.05or P<0.01）.Conclusion: I3C could attenuate bleomycin-induced pulmonary fibrosis in mice and rats. The mechanisms might be related with the anti-oxidatant, the anti-inflammatory,inhibition of collagen formation and the regulation of TGF-β1/Smad signal pathway.