Abstract
ObjectivesSIRT1 is an antioxidative factor, but its mechanism in methamphetamine (MA)‐induced lung injury remains unclear. The purpose of this study is to determine whether MA can disrupt the integrity of alveolar epithelial barrier, whether SIRT1 is involved in MA‐induced chronic lung injury and whether Resveratrol (Res) can protect the integrity of alveolar epithelial cells by regulating ROS to activate SIRT1/PTEN/p‐Akt pathway.Materials and methodsThe rats were randomly divided into control group and MA group. Extracted lungs were detected by Western blot, HE staining and immunohistochemistry. The alveolar epithelial cells were treated with MA or/and Res, following by Western blot, LDH leakage assay and flow cytometry. MOE is used for bio‐informatics prediction.ResultsChronic exposure to MA can cause slower growth ratio of weight, increased RVI and induced lung injury including the reduced number of alveolar sacs and the thickened alveolar walls. MA‐induced apoptosis was associated with SIRT1‐related oxidative stress. Res suppressed ROS levels, activated SIRT1, negatively regulated PTEN, phosphorylated Akt, reduced LDH leakage, increased the expression of ZO‐1 and E‐cadherin and inhibited the apoptosis of alveolar epithelial cells to attenuate MA‐induced higher permeability of alveolar epithelium.ConclusionsMA disrupted the integrity of alveolar epithelial barrier. Res inhibited oxidative stress and reversed MA‐induced higher permeability and apoptosis of alveolar epithelium by the activation of SIRT1/PTEN/p‐Akt pathway.
Highlights
Methamphetamine (MA) is a greatly addictive drug.[1]
These results indicated that chronic exposure of MA can increase the permeability of cell epithelium to disrupt the barrier function of alveolar epithelium
These results were confirmed that SIRT1 expression and apoptosis of alveolar epithelial cells were modulated by MA-induced oxidative stress
Summary
Methamphetamine (MA) is a greatly addictive drug.[1] MA is abused by snorting, smoking and injection It is well-absorbed in pulmonary alveoli.[2] Alveolar epithelium plays an essential role in maintaining the pulmonary homoeostasis.[3] Higher uptake rate of MA in lungs suggests that lung is a primary target for MA-related injury.[4] It was reported that MA could increase the ROS levels in rat lungs.[5,6] Excessive accumulation of ROS induces alveolar epithelial apoptosis and even pulmonary toxicity.[5] disruption of alveolar epithelial integrity is the key to chronic lung injury induced by MA. Lung injury was calculated by the thickness of alveolar septum and the number of alveolar sacs (three visual fields selected randomly were analysed in each section; magnification, ×200 and ×400).[24]
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