Department of Clinical Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.
Department of Drug Control, Criminal Investigation Police, University of China, Shenyang, China.
Cell Prolif. 2020 Mar;53(3):e12773. doi: 10.1111/cpr.12773. Epub 2020 Feb 5.
SIRT1 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.
The 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.
Chronic 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.
MA 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.
SIRT1 是一种抗氧化因子，但它在甲基苯丙胺（MA）诱导的肺损伤中的作用机制尚不清楚。本研究旨在确定 MA 是否会破坏肺泡上皮细胞屏障的完整性，SIRT1 是否参与 MA 诱导的慢性肺损伤，以及白藜芦醇（Res）是否可以通过调节 ROS 来激活 SIRT1/PTEN/p-Akt 通路来保护肺泡上皮细胞的完整性。
将大鼠随机分为对照组和 MA 组。通过 Western blot、HE 染色和免疫组织化学检测提取的肺组织。用 MA 或/和 Res 处理肺泡上皮细胞，然后进行 Western blot、LDH 漏出测定和流式细胞术。MOE 用于生物信息学预测。
慢性暴露于 MA 可导致体重增长速度减慢、RVI 增加，并引起肺损伤，包括肺泡囊数量减少和肺泡壁增厚。MA 诱导的细胞凋亡与 SIRT1 相关的氧化应激有关。Res 抑制 ROS 水平，激活 SIRT1，负调控 PTEN，磷酸化 Akt，减少 LDH 漏出，增加 ZO-1 和 E-cadherin 的表达，抑制肺泡上皮细胞凋亡，从而减轻 MA 诱导的肺泡上皮通透性增加。
MA 破坏了肺泡上皮细胞屏障的完整性。Res 通过激活 SIRT1/PTEN/p-Akt 通路抑制氧化应激，逆转 MA 诱导的肺泡上皮通透性增加和细胞凋亡。
