Oxidative stress and inflammatory processes are proposed to mediate the development of silicosis. However, antioxidant therapy has not produced consistent results during the treatment of silicosis. α-Lipoic acid synthesized by lipoic acid synthase is a powerful anti-oxidant and helps protect mitochondria. Thus far, the effect of endogenous α-Lipoic acid on silicosis has not been elucidated yet. We established an experimental model of silicosis with wildtype and LiasH/H mice, a new antioxidant mouse model which has overexpressed Lias gene (∼150%) relative to its wild type counterpart. We systemically examined main pathological changes of pulmonary fibrosis, and explored α-lipoic acid effects on oxidative stress, inflammatory and pulmonary fibrosis biomarkers in silica-instillated mice. In LiasH/H mice over-expression of lipoic acid alleviated the severity of major pathological alterations in the early stage of pulmonary fibrosis induced by silica compared with wild type mice. Silica significantly increased oxidative stress in both wild type and LiasH/H mice. The antioxidant defense was strengthen including increased NRF2 and LIAS production in LiasH/H mice. Relieved oxidative stress resulted in decreased inflammatory response and secretion of chemokines. LiasH/H mice reduced chronic inflammatory response and inhibition of NF-κB activity after silica instillation. The LiasH/H mouse model overexpression of lipoic acid synthase gene retarded the development of silica-induced pulmonary fibrosis. Strengthen antioxidant defense by increased lipoic acid synthase is a potential strategy for protection against silica-induced pulmonary fibrosis.

中文翻译：

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内源性硫辛酸合酶的过度表达减轻由结晶二氧化硅诱导的小鼠肺纤维化

氧化应激和炎症过程被提议介导矽肺的发展。然而，抗氧化疗法在矽肺的治疗过程中并没有产生一致的结果。硫辛酸合成酶合成的α-硫辛酸是一种强大的抗氧化剂，有助于保护线粒体。迄今为止，内源性α-硫辛酸对矽肺的影响尚未阐明。我们用野生型和 LiasH/H 小鼠建立了矽肺实验模型，这是一种新的抗氧化小鼠模型，相对于其野生型对应物，Lias 基因过表达（~150%）。我们系统地检查了肺纤维化的主要病理变化，并探讨了 α-硫辛酸对二氧化硅灌注小鼠氧化应激、炎症和肺纤维化生物标志物的影响。在 LiasH/H 小鼠中，与野生型小鼠相比，硫辛酸的过度表达减轻了二氧化硅诱导的肺纤维化早期主要病理改变的严重程度。二氧化硅显着增加了野生型和 LiasH/H 小鼠的氧化应激。抗氧化防御得到加强，包括在 LiasH/H 小鼠中增加 NRF2 和 LIAS 的产生。缓解氧化应激导致炎症反应和趋化因子分泌减少。LiasH/H 小鼠在二氧化硅滴注后减少了慢性炎症反应和 NF-κB 活性的抑制。硫辛酸合酶基因的 LiasH/H 小鼠模型过表达延缓了二氧化硅诱导的肺纤维化的发展。