Effects Of Metformin On Expression Of AMPK And LC3-? In Lung Tissues Of Rats With Pulmonary Fibrosis

Objective: To investigate the effects of metformin on expression of AMPK and LC3-? in lung tissues of rats with pulmonary fibrosis.Methods: 40 SD male rats of body weight 180.0~200.0g were fed at the center room of experimental animals(grade SPF)of Zunyi Medical College.They were free to eat and drink for 1 week.They were randomly divided into 5 groups(control group,model group,metformin group,pifimenone group,metformin + pifafenone group),8 rats in each group.The control group was given a single intratracheal injection of 0.9% normal saline 2ml/Kg,and the other groups were given a single intratracheal intratracheal injection of bleomycin5mg/Kg to establish a pulmonary fibrosis model.After 7 days,the corresponding drugs were given(0.9% normal saline 5ml/Kg,0.9% physiological saline 5ml/Kg,metformin500mg/Kg,pifimenone 50mg/Kg,metformin 500mg/Kg+ pifafenone 50mg/Kg)for 21 days,and the rats were killed on the twenty-second day(rats had been fasting for 24 hours).The changes of inflammation and fibrosis in lung tissues of rats were observed by HE and Masson staining images.The content of AMPK,HYP and TGF-beta 1 in lung tissues homogenate were measured by enzyme linked immunosorbent assay.The content of LC3-? in lung tissues were measured by immunohistochemical.Results: Rats with pulmonary fibrosis were successfully replicated.Compared with the control group,the expression of HYP and TGF-beta 1 and the semi quantitative scores of HE and Masson staining images in the lung tissues of the model group were increased,the expression of AMPK were decreased,the difference was statistically significant(P<0.05),the expression of LC3-? content in the lung tissues of the model group were increased,the difference was not statistically significant(P > 0.05).Compared with the model group,the levels of HYP and TGF-?1 in the lung tissues of the metformin group,pirfenidone group,and pirfenidone + metformin group and the semi-quantitative scores of the lung tissues with HE and Masson staining were decreased,AMPK content were increased,the difference was statistically significant(P<0.05).The expression of LC3-? in the lung tissues of metformin group and pifimidone + metformin group were increased.the difference was statistically significant(P < 0.05).Compared with the single drug group,the expression of TGF-beta 1 and HYP in the lung tissues of the combined drug group and and the semi quantitative scores of HE and Masson in lung tissues were decreased,the content of AMPK and LC3-? were increased,the difference was not statistically significant(P > 0.05).Conclusion:1.Metformin can reduce pulmonary inflammation and delay the progression of pulmonary fibrosis,but metformin combined with pifimidone has no significant difference compared with metformin alone.2.Metformin can up regulate the expression of AMPK and LC3-? in lung tissues of rats with pulmonary fibrosis.