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目的 探究脂质运载蛋白2(LCN2)在矽肺纤维化中的调控作用，并利用其高选择性LCN2抑制剂ZINC00640089进行干预。方法 将32只SPF级C57BL/6雄性小鼠随机分为对照组、ZINC00640089组、矽肺组和矽肺+ZINC00640089组，每组8只。通过气管灌注50 μL二氧化硅(SiO2， 1×105 mg/L)混悬液制备小鼠矽肺模型。ZINC00640089组和矽肺+ ZINC00640089组小鼠分别腹腔注射浓度为2×103 mg/L的ZINC00640089 100 μL，对照组小鼠注射等体积的生理盐水。于第4周处死小鼠，采集小鼠肺组织及血浆，采用苏木精-伊红染色(HE)和苦味酸-酸性品红染色(VG)观察小鼠肺组织病理情况，利用脂质代谢组学筛选血浆脂质差异代谢物及富集途径。Western blot检测脂质代谢功能型标志物胆碱磷酸转移酶 1(CHPT1)的蛋白表达水平。结果 与对照组比较，矽肺组见明显矽结节及胶原沉积，ZINC00640089干预后结节缩小、胶原减少；代谢组学筛选出对照组和矽肺组中有9个差异代谢物，矽肺组和矽肺+ZINC00640089组中有6个差异代谢物。两个比较组差异代谢物均主要富集在甘油磷脂代谢通路。对甘油磷脂代谢通路中的CHPT1进行验证，与矽肺组比较，矽肺+ZINC00640089组的CHPT1表达升高(P=0.015)。结论 LCN2可能通过调控甘油磷脂代谢通路改善 SiO2诱导的脂质代谢紊乱。
Abstract：Objective To investigate the regulatory role of Lipocalin 2 (LCN2) in silicosis-induced pulmonary fibrosis， we employed ZINC00640089， a highly selective inhibitor of LCN2， for intervention. Methods 32 SPF-grade C57BL/6 male mice were randomly divided into the control group， the ZINC00640089 group， the silicosis group， and the silicosis + ZINC00640089 group， with 8 mice in each group. The silicosis model of mice was prepared by intratracheal instillation of 50 μL of 1×105 mg/L SiO2 suspension. The ZINC00640089 group and the silicosis + ZINC00640089 group were intraperitoneally injected with 100 μL of 2×103 mg/L ZINC00640089， while the control group was injected with the same volume of normal saline. The mice were sacrificed at the 4th week， and the lung tissues and plasma of the mice were collected. The pathological conditions of the lung tissues of the mice were observed by HE and VG staining， and the differential metabolites and enriched pathways of plasma lipids were screened using lipidomics. The protein expression level of the lipid metabolism functional marker choline phosphate transferase 1 (CHPT1) was detected by Western blot. Results Compared with the control group， the silicosis group showed obvious silicotic nodules and collagen deposition. After ZINC00640089 intervention， the nodules shrank and the collagen decreased. Nine differential metabolites were screened out in the control group and the silicosis group， and 6 differential metabolites were found in the silicosis group and the silicosis + ZINC00640089 group. The differential metabolites in the two comparison groups were mainly enriched in the glycerophospholipid metabolism pathway. The CHPT1 in the glycerophospholipid metabolism pathway was verified， and compared with the silicosis group， the CHPT1 expression in the silicosis + ZINC00640089 group was increased (P=0.015). Conclusion LCN2 may improve lipid metabolism disorders induced by SiO2 through regulating the glycerophospholipid metabolism pathway.
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基本信息:
中图分类号:R135.2
引用信息:
[1]张越,戚荣,万方泽,等.基于血浆脂质组学探究LCN2调控矽肺脂质代谢的作用[J].安徽医科大学学报().
基金信息:
国家自然科学基金项目（编号：U21A20334）; 河北省自然科学基金项目（编号：H2025209083、H2025209038）; 河北省高等学校科学研究项目（编号：QN2026045）
2026-08-31
2026-08-31
2026-08-31