雷公藤甲素通过周细胞EMT-like通路改善百草枯诱导的小鼠肺纤维化及其作用机制OA

Objective To explore the improvement effect and mechanism of triptolide on paraquat-induced pulmonary fibrosis in mice through pericytes.Methods Sixty male C57BL/6 mice were randomly assigned to five groups,with 12 mice in each group:a blank control group,a model group,a low-dose triptolide group,a medium-dose triptolide group,and a high-dose triptolide group.A pulmonary fibrosis model was established using paraquat.The effects of the drug on body weight,lung coefficient,and collagen content in lung tissue were investigated.Lung tissue sections were scored based on indicators such as inflammatory cell infiltration and the degree of pulmonary interstitial fibrosis.The content of hydroxyproline(Hyp)was measured,and changes in serum levels of reduced glutathione(GSH),nitric oxide(NO),superoxide dismutase(SOD),malondialdehyde(MDA),and inflammatory factors were detected.Immunohistochemistry and Western blot techniques were used to systematically evaluate the regulatory effect of triptolide on epithelial-mesenchymal transition(EMT)markers,and changes in the relative expression levels of TGF-β1,Smad homolog 3(Smad3)mRNA and protein were observed.Results The content of Hyp in the lung tissue of mice in the model group was significantly higher than that in the control group(P<0.01).The Hyp content in the low,medium,and high-dose triptolide groups were reduced compared to the model group(P<0.05).Compared with the low and medium-dose triptolide groups,the Hyp content in the lung tissue of mice in the high-dose triptolide group was further decreased(P<0.05).Significant differences were observed in the levels of serum GSH,NO,SOD,and MDA among the groups of mice.Compared to the control group,the expression levels of IL-1β,IL-18,and TNF-α in the lung tissue of mice in the model group were significantly increased(P<0.01).Compared to the model group,the expression levels of IL-1β,IL-18,and TNF-α in the lung tissue of mice in the low,medium,and high-dose triptolide groups were significantly decreased(P<0.05).Compared to the low and medium-dose triptolide groups,the expression levels of IL-1β,IL-18,and TNF-α in the lung tissue of mice in the high-dose triptolide group were further decreased(P<0.05).Compared to the control group,the mRNA and protein expression levels of TGF-β1 and Smad3 in the alveolar microvascular pericytes of mice in the model group were increased(P<0.01).The mRNA and protein expression levels of TGF-β1 and Smad3 in the alveolar microvascular pericytes of mice in the low,medium,and high-dose triptolide groups were lower than those in the model group(P<0.05).Furthermore,compared to the low and medium-dose triptolide groups,the mRNA and protein expression levels of TGF-β1 and Smad3 in the alveolar microvascular pericytes of mice in the high-dose triptolide group were further decreased(P<0.05).Conclusion This study demonstrated that triptolide regulates the pericyte EMT-like pathway and targets TGF-β1 to play an anti-pulmonary fibrosis role.