It is growingly concerned about methamphetamine (MA)‐induced lung toxicity. IMP1 is identified as a key molecule for cell life processes, but the role of IMP1 in MA‐induced senescence remains unclear. The purpose of this study was to investigate whether chronic exposure to MA can cause autophagy and senescence of the lungs, whether there are interactions between Mammalian target of rapamycin (mTOR) and IMP1 and whether IMP1 is involved in pulmonary senescence promoted by mTOR‐autophagy. The rats were randomly divided into control group and MA group, following by H&E staining, immunohistochemistry staining and Western blot. The alveolar epithelial cells were proceeded by ß‐galactosidase staining, cell cycle detection, transfection and co‐immunoprecipitation. Long‐term exposure to MA led to the thickening of alveolar septum and more compact lungs. MA promoted the conversion of LC3‐I to LC3‐II and inhibited the activation of mTOR to induce autophagy. Bioinformatics and co‐immunoprecipitation results presented the interactions between IMP1 and mTOR. MA induced cell senescence by decreasing IMP1, up‐regulating p21 and p53, arresting cell cycle and increasing SA‐β‐gal. Overexpression of IMP1 reduced p21 and SA‐β‐gal to inhibit the senescence of alveolar epithelial cells. These results demonstrated that mTOR‐autophagy promotes pulmonary senescence through IMP1 in chronic toxicity of methamphetamine.

中文翻译：

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mTOR自噬通过甲基苯丙胺的慢性毒性通过IMP1促进肺衰老。

人们越来越担心甲基苯丙胺（MA）引起的肺毒性。IMP1被认为是细胞生命过程的关键分子，但尚不清楚IMP1在MA诱导的衰老中的作用。这项研究的目的是调查长期暴露于MA是否会引起肺部自噬和衰老，雷帕霉素的哺乳动物靶标（mTOR）和IMP1之间是否存在相互作用以及IMP1是否参与mTOR自噬促进的肺衰老。H＆E，免疫组化，Western blot法将大鼠随机分为对照组和MA组。在肺泡上皮细胞通过β-半乳糖苷染色，细胞周期检测，转染和共进行-免疫沉淀。长期接触MA会导致肺泡隔膜增厚和肺部更紧实。MA促进了LC3-I向LC3-II的转化，并抑制了mTOR的激活以诱导自噬。生物信息学和合作-免疫效果呈现IMP1和mTOR之间的相互作用。MA通过降低IMP1，上调p21和p53，阻滞细胞周期并增加SA-β-gal来诱导细胞衰老。IMP1的过表达降低了p21和SA-β-gal的表达，从而抑制了肺泡上皮细胞的衰老。这些结果表明，mTOR自噬在甲基苯丙胺的慢性毒性中通过IMP1促进肺衰老。