Rhein attenuates bleomycin-induced rats pulmonary fibrosis through TGF-β1/Smad pathway by inhibiting miR-21 expression / 中国病理生理杂志

ABSTRACT

AIM:To investigate the effect of rhein on bleomycin-induced pulmonary fibrosis and the expression of microRNA-21 (miR-21) and transforming growth factor-β1 (TGF-β1)/Smad signaling molecules in rats.METHODS:A single dose of bleomycin was intratracheal injected into the SD rats to induce pulmonary fibrosis .After injection of bleo-mycin, the rats were randomly divided into low-, medium-and high-dose rhein treatment groups and model group .The rats that were instilled with normal saline intratracheally served as control group .After the treatment for 28 d, the pulmonary pathologic changes were observed under microscope with hematoxylin-eosin staining .The lung coefficient and hydroxypro-line content were also measured .The expression of miR-21 and the mRNA levels of TGF-β1 and Smad7 in the lung tissues were detected by real-time PCR.The protein levels of TGF-β1 and Smad7 were determined by Western blot .RESULTS:Rhein significantly attenuated the experimental alveolitis , pulmonary fibrosis , lung coefficient and hydroxyproline contents in the rats.Rhein obviously decreased the expression of miR-21,and the mRNA and protein levels of TGF-β1, but signifi-cantly increased the mRNA and protein levels of Smad 7 in the lung tissues .CONCLUSION: Rhein effectively prevents bleomycin-induced pulmonary fibrosis by inhibiting the expression of miR-21 and promoting the expression of Smad 7, thus regulating the TGF/Smad signaling pathway to decrease extracellular matrix deposition .