Effects of Polydatin on Immune Inflammatory and Metabolic Injury in a Mouse Model of Interstitial Lung Disease
Objective To investigate the protective effect and mechanism of polydatin(PD)on bleomycin(BLM)-induced interstitial lung disease(ILD)in mice.Methods The mouse model of ILD was established in SPF-grade male C57BL/6J mice,with a body weight of(20±2)g,by intratracheal instillation of BLM(2 mg/kg).The 30 mice successfully modeled were randomly divided into model group,positive drug group,high,medium and low dose PD groups,with 6 mice in each group.Six male C57BL/6J mice without modeling were set as normal control group.The mice in the normal control group and model group were given deionized water at a dose of 10 ml/(kg·d).The mice in the positive drug group were given prednisone at a dose of 7.5 mg/(kg·d).The mice in the high,medium and low PD groups were respectively given PDat doses of 200,100,and 50 mg/(kg·d).The mice in each group were subjected to intragastric administration once a day,and the high dose group PD was given twice a day.The mice were euthanized,and lung tissue samples were collected after 4 weeks of continuous intervention.Hematoxylin-eosin(HE)staining method was used to assess pathological changes of the lung tissue in each group of mice.RT-PCR was employed to detect the mRNA transcription levels of AMPKα1,PPARγ,and PGC-1α in the lung tissue.Western blot was conducted to detect the protein expression levels of AMPKα1,pAMPKα1,PPARγ,PGC-1α,HMGB1,TGF-β1,and NF-κB p65 in the lung tissue.Results Compared with the nor-mal control group,the mice in the model group had obvious pathological changes(P＜0.01),mainly characterized by in-flammatory cell infiltration and interstitial fibrosis in lung tissue.Compared with the model group,the inflammatory lesions of lung tissue in the positive drug group were improved(P＜0.05),and the mice in the PD treatment groups showed im-provement in lung tissue inflammatory cell infiltration and interstitial fibrosis compared to the model group(P＜0.05).The results from RT-PCR indicated a decreasing trend in the mRNA transcription levels of AMPKα1,PPARγ,and PGC-1αin the lung tissue of mice in the model compared to the normal control group.The mice in the positive drug group and the PD treatment groups showed an increasing trend in the mRNA transcription levels of AMPKα1,PPARγ,and PGC-1α in lung tissue compared to the model group.However,there were no significant differences between the positive drug group and the PD treatment groups.Compared with the normal control group,the HMGB1 and NF-κB p65 protein expressions were up-regulated(P＜0.01),and AMPKα1,pAMPKα1,PPARγ and PGC-1α protein expressions were down-regula-ted(P＜0.05)in the model group.Compared with the model group,the positive drug group and high dose PD group showed a significant increase in AMPKα1 protein expression levels(P＜0.05),the high and low dose PD groups showed a signifi-cant increase in pAMPKα1 levels(P＜0.05),and the medium dose PD group showed a significant increase in PPARγ pro-tein expression levels(P＜0.05).The protein expression levels of HMGB1 and NF-κB p65 significantly decreased in the positive drug group and low dose PD group(P＜0.05),while the other treatment groups showed a decreasing trend com-pared to the model group.There were no significant differences observed in the changes between the positive drug group and the PD treatment groups.Conclusion PD can improve the pathological inflammatory damage and interstitial fibrosis in the lung tissue of CTD-ILD model mice,and inhibit immune-inflammatory injury.The mechanism may involve the ac-tivation of AMPKα1/PPARγ/PGC-1α signaling pathway,which inhibits the overexpression of downstream immune in-flammatory factors HMGB1 and NF-κB,thereby improving the immune inflammatory injury of lung tissue.PD may also in-hibit the release of fibrotic cytokine TGF-β1 and alleviate immune-inflammatory injury and interstitial fibrosis in lung tissue.
万方数据
维普
