Study On The Effect And Mechanism Of Bergenin On Improving The Symptoms Of Pulmonary Fibrosis In Mice

Idiopathic pulmonary fibrosis is a chronic progressive disease,and once patients are diagnosed with idiopathic pulmonary fibrosis,their median survival is approximately 3-5 years.There is a lack of drugs for the treatment of idiopathic pulmonary fibrosis,and the irreversible progression of fibrosis symptoms places a heavy medical and nursing burden on patients.Bergenin is an isocoumarin compound with multiple biological functions,with cough-expectorant effects and antioxidant activity,has not been investigated in idiopathic pulmonary fibrosis.Aims:(1)To investigate the effect of bergenin on improving the symptoms of pulmonary fibrosis.(2)To investigate the therapeutic effect of bergenin on pulmonary fibrosis.(3)To investigate the mechanism of bergenin in improving the symptoms of idiopathic fibrosis and treating pulmonary fibrosis.Methods:(1)A mouse model of pulmonary fibrosis was constructed by intratracheal injection of bleomycin,and different concentrations of bergenin were injected intraperitoneally for intervention.(2)The BUXCO system was used to detect lung function in mice,and the expression levels of Muc5 ac and Muc5 b in lung tissues were detected by Q-PCR.(3)WB and Q-PCR were used to detect the expression levels ofα-SMA,collagen Ⅰ,HO-1 and NQO1.(4)Using DHE staining to detect ROS content in lung tissue.(5)Different concentrations of bergenin were added and incubated during the transformation of fibroblasts into myofibroblasts induced by TGF-β1.(6)WB and Q-PCR were used to detect cellular expression levels ofα-SMA,collagen Ⅰ,HO-1 and NQO1.(7)NIH3T3 cells were incubated with TGF-β1 and different concentrations of bergenin,and the cellular ROS content was detected by DCFH-DA probe.(8)Nrf2 si RNA and p62 si RNA treated NIH3T3 cells were co-incubated with bergenin and the expression levels of α-SMA,collagen Ⅰ,HO-1 and NQO1 were detected by WB and Q-PCR.Results:(1)Bergenin improved lung function indexes such as lung compliance,lung resistance and respiratory rate in lung fibrosis mice.(2)Bergenin decreased the expression levels of Muc5 b,Muc5ac,α-SMA and collagen Ⅰ and increased the expression levels of HO-1 and NQO1 in lung tissues of lung fibrosis mice.(3)Bergenin decreased the levels of ROS in lung tissue of lung fibrosis mice.(4)Bergenin inhibited the expression levels of α-SMA and collagen Ⅰ and increased the expression levels of HO-1 and NQO1 during myofibroblast transformation.(5)Bergenin recuded the levels of ROS during the myofibroblast transformation of NIH3T3 cells.(6)Bergenin promoted the expression levels of p62 and P-p62 in NIH3T3 cells.(7)The effect of bergenin on α-SMA,collagen Ⅰ,HO-1 and NQO1 expression was suppressed after p62 and Nrf2 silencing.Conclusions:(1)bergenin improved the symptoms of pulmonary fibrosis in mice.(2)Bergenin is an effective treatment for pulmonary fibrosis.(3)The p62-Nrf2 regulatory loop mediates the anti-pulmonary fibrosis effect and antioxidant action of bergenin.