矽肺是长期吸入大量二氧化硅粉尘引起的常见职业病。脂代谢在矽肺的进展中起重要作用,但其作用机制尚不清楚。本研究的目的是研究矽肺大鼠肺组织中的差异脂质代谢产物和活性代谢途径。我们首先构建了矽肺大鼠模型,将24只雄性SD大鼠随机分为对照组(C组),矽肺组1周(S1W),矽肺组2周(S2W),矽肺组4周(S4W),每组6只。将1mlSiO2混悬液(50mg/ml)或生理盐水注入气管,老鼠在1周时被杀死,2周4周,分别。HE染色和VG染色观察大鼠肺组织病理,试剂盒检测血浆TC和FC水平。Westernblot检测脂质相关因子CD36、PGC1α和LXR的表达。此外,使用UPLC-IMS-QTOF质谱仪对肺组织样本进行脂质组学分析,以筛选出矽肺模型中潜在的差异代谢物并分析脂质富集,并验证了差异基因CHPT1在代谢通路中的表达。HE和VG染色显示矽肺模型组结节数量和纤维化呈时间依赖性增加,和TC的水平,矽肺血浆中FC和CE升高。Westernblot结果显示,矽肺模型组PGC1α和LXR降低,而CD36表达增加。此外,代谢组学在S1W组中筛选出28种差异代谢物,32在S2W组中,S4W组中有22人,发现差异代谢产物主要富集在甘油磷脂代谢和醚脂代谢等代谢途径中,矽肺模型组代谢通路中差异基因CHPT1的表达降低。这些结果提示矽肺模型大鼠肺组织脂质代谢产物有显著变化,甘油磷脂代谢显著富集,表明甘油磷脂在矽肺的进展中起重要作用。本研究报道的差异代谢产物和通路可能为矽肺的发病机制提供新的思路。
Silicosis is a common occupational disease caused by the long-term inhalation of large amounts of silica dust. Lipid metabolism plays an important role in the progression of silicosis, but its contributing mechanism remains unclear. The aim of this study was to investigate the differential lipid metabolites and active metabolic pathways in silicosis rat lung tissue. We first constructed a silicosis rat model, and randomly divided 24 male SD rats into control group (C), silicosis group for 1 week (S1W), silicosis group for 2 weeks (S2W) and silicosis group for 4 weeks (S4W) with 6 rats in each group. 1 mL SiO2 suspension (50 mg/mL) or normal saline were injected into the trachea, and the rats were killed at 1 week, 2 weeks and 4 weeks, respectively. The lung tissue pathology of the rats was observed by HE staining and VG staining, and the plasma TC and FC levels were detected by the kit. Western blot was used to detect the expression of lipid-related factors CD36, PGC1α and LXR. In addition, lipidomics analysis of lung tissue samples was performed using UPLC-IMS-QTOF mass spectrometer to screen out potential differential metabolites in silicosis models and analyze lipid enrichment, and verified the expression of differential gene CHPT1 in the metabolic pathway. HE and VG staining showed that the number of nodules and fibrosis increased in a time-dependent manner in the silicosis model group, and the levels of TC, FC and CE in silicosis plasma increased. Western blot results showed that PGC1α and LXR decreased in the silicosis model group, while CD36 expression increased. In addition, metabolomics screened out 28 differential metabolites in the S1W group, 32 in the S2W group, and 22 in the S4W group, and found that the differential metabolites were mainly enriched in metabolic pathways such as glycerophospholipid metabolism and ether lipid metabolism, and the expression of differential gene CHPT1 in the metabolic pathway was decreased in the silicosis model group. These results suggest that there are significant changes in lipid metabolites in lung tissue in silicosis rat models, and glycerophospholipid metabolism was significantly enriched, suggesting that glycerophospholipids play an important role in the progression of silicosis. The differential metabolites and pathways reported in this study may provide new ideas for the pathogenesis of silicosis.