Bufei-Yishen formula mitigates mitochondrial damage in rats with chronic obstructive pulmonary disease by regulating AMPK/PGC-1α signaling pathway
10.3969/j.issn.1000-4718.2025.11.015
- VernacularTitle:补肺益肾方通过调控AMPK/PGC-1α信号通路减轻慢性阻塞性肺疾病大鼠线粒体损伤
- Author:
Li MA
1
;
Zhengyuan FAN
;
Ya LI
;
Gaofeng LI
;
Zihan SHEN
;
Suyun LI
Author Information
1. 河南中医药大学第一附属医院呼吸科,河南 郑州 450000;河南中医药大学第一临床医学院,河南 郑州 450000
- Publication Type:Journal Article
- Keywords:
Bufei-Yishen formula;
chronic obstructive pulmonary disease;
mitochondrial damage;
AMPK/PGC-1α signaling pathway
- From:
Chinese Journal of Pathophysiology
2025;41(11):2200-2209
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study aimed to explore the mechanism by which Bufei-Yishen formula(BYF)mitigates mitochondrial damage in rats with chronic obstructive pulmonary disease(COPD)by regulating the AMPK/PGC-1α signal-ing pathway.METHODS:Forty rats were randomly divided into four groups,each containing ten rats each:control group,COPD group,BYF group,and N-acetylcysteine(NAC)group.The COPD model was established through chronic cigarette smoke exposure combined with periodic bacterial inoculations over an eight-week induction phase.During the subsequent eight-week treatment period(i.e.,weeks 9～16),rats in the control and COPD groups received an isovolumet-ric saline solution via oral gavage,at a standardized daily dose of 2 mL per animal.Moreover,rats in the BYF and NAC groups were given Bufei Yishen formula(11.61 g·kg-1·d-1)or N-acetylcysteine(54 mg·kg-1·d-1)by gavage,once per day.At week 16,samples were collected and the general condition of the rats was observed.Body weight was recorded weekly.We also obtained data characterizing rat lung function,lung pathology,ATP content,and mitochondrial ultra-structure,as well as the levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),se-rum transforming growth factor-beta 1(TGF-β1)and the enzymatic activities of mitochondrial electron transport chain complexes I(NADH dehydrogenase)and III(cytochrome c reductase).Finally,we quantified the mRNA and protein lev-els of AMPK and PGC-1α in lung tissue.RESULTS:Compared to the control group,the COPD group exhibited yellow-ish hair color,reduced gloss,slower weight gain,and a disordered respiratory rhythm.We also observed significant de-creases(P<0.01)in pulmonary function tidal volume(TV),minute ventilation(MV),peak expiratory flow(PEF),expi-ratory flow at 50%of tidal volume(EF50),forced vital capacity(FVC),forced expiratory volume in 0.1 s(FEV0.1),and FEV0.1/FVC.Histopathological analysis showed alveolar cavity enlargement,bullous changes in lung morphology,smooth muscle hypertrophy in the tracheal wall,ciliary destroyed,mucosal shrinking and thickening,and a large number of in-flammatory cells gathered around the tube.Moreover,the mean linear intercept(MLI)and bronchial wall thickness(BWt)had both significantly increased(P<0.01).Electron microscopic analysis of the lungs revealed a reduction in the number of mitochondria in alveolar epithelial cells,a swollen and deformed lung morphology overall.We observed that the mitochondrial cristae were broken,dissolved or vacuolated,accompanied by a significant reduction in the number of lamel-lar bodies and lung volume,along with a disordered internal lipid layer structure.Furthermore,some lung samples were vacuolated or had content leakage.Further quantitative analyses showed statistically significant increases(P<0.01)in the levels of serum pro-inflammatory mediators,including IL-6,TNF-α,IL-1β,and TGF-β1.At the same time we observed substantial reductions in the enzymatic activities of mitochondrial electron transport chain complexes I and III(P<0.01).Moreover,we found that metabolic impairment correlated with significantly attenuated ATP production(P<0.01)in exper-imental subjects.Moreover,the expression levels of AMPK and PGC-1α mRNA and proteins in lung tissue were signifi-cantly decreased(P<0.01).Moreover,compared to the COPD group,the BYF group showed significant improvements in several of the above indicators,albeit to different degrees(P<0.01 or P<0.05).Moreover,BYF was more effective than NAC in improving minute ventilation and up-regulating PGC-1α expression(P<0.05).CONCLUSION:Bufei-Yishen formula may ameliorate mitochondrial damage in rats with chronic obstructive pulmonary disease by regulating the AMPK/PGC-1α signaling pathway.
