ABSTRACT
Chronic obstructive pulmonary disease (COPD) has always attracted global attention with its high prevalence, incidence rate, and mortality. Exposure to cigarette smoke is one of main causes of COPD. Therefore, it is still necessary to study its pathogenesis and find new therapeutic strategies for early COPD prevention and treatment. Vardenafil, a type 5 phosphodiesterase (PDE5) inhibitor, is known to have an efficient therapy in some cardiovascular, pulmonary, and vascular diseases, which is an important mechanism for COPD. However, it still loss relevant research on whether vardenafil is effective in COPD and its mechanism. In this study, the cigarette smoke inhalation was performed to establish cigarette smoke-induced COPD model using C57BL/6 mice and 16HBE cells were treated with cigarette smoke extract (CSE). Mice were treated with vardenafil for 30 d. Then condition of lung injury was evaluated using histological analysis. The content of cytokines and the number of inflammatory cells in lung tissues or bronchoalveolar lavage fluid were measured. Additionally, western blot analysis was employed to evaluate the activation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR)-mediated autophagy in vitro. The results showed that vardenafil abolished CSE's effect by activating autophagy via the AMPK/mTOR signalling pathway in vitro. Vardenafil attenuated cigarette smoke-induced lung injury and inflammation response by activating autophagy via the AMPK/mTOR signalling pathway in vivo. These results provide valuable insights into the molecular mechanisms underlying vardenafil's beneficial effects in cigarette smoke-induced COPD treatment. In conclusion, vardenafil alleviates cigarette smoke-induced experimental COPD by activating autophagy via the AMPK/mTOR signalling pathway.
Subject(s)
Cigarette Smoking , Lung Injury , Pulmonary Disease, Chronic Obstructive , Vardenafil Dihydrochloride , Animals , Mice , AMP-Activated Protein Kinases/metabolism , Autophagy , Cigarette Smoking/adverse effects , Mice, Inbred C57BL , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/etiology , TOR Serine-Threonine Kinases/metabolism , Vardenafil Dihydrochloride/therapeutic useABSTRACT
OBJECTIVE: To investigate the relationship between the renal tubular function and the severity of tubulo interstitial lesion and the effects of Astragalus Injection (AI) on renal tubular function in patients with IgA nephropathy (IgAN). METHODS: Sixty-seven patients with IgAN were randomly divided into the control group and the astragalus group, both received dipyridamole and benazepril orally, while the astragalus group treated with AI by intravenous dripping additionally. The indices for renal tubular function, including protein in blood and urine, urinary retinol binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (UNAG), were detected. Area of glomerular Bowman capsule, renal tubules, and capillary were measured with color magic image analysis system type CMIAS2000. RESULTS: Urinary RBP and UNAG were correlated with tubulointerstitial lesion. Urine protein concentration decreased, blood albumin increased remarkably and renal tubular function improved after treatment in the astragalus group, with the improvement significantly different to those in the control group respectively. CONCLUSION: The severity of tubulointerstitial lesion was positively related to urinary RBP concentration, and astragalus injection has obvious effect on IgAN.
