Gong Xinyi, Fan Jingchuan, Huang Hui, Xu Fei, Hu Kaijiao, Liu Jianping, Tan Yi, Chen Feilan
Laboratory Animal Center, Chongqing Medical University, Chongqing 400016, China.
Chongqing Engineering Research Center for Rodent Laboratory Animals, Chongqing 400016, China.
Biomedicines. 2025 Mar 28;13(4):821. doi: 10.3390/biomedicines13040821.
: Identifying effective and safe treatment options for non-infectious uveitis remains challenging due to chronic and relapsing ocular inflammation. Previous studies have shown that artesunate (ART) plays an immunosuppressive role in several classic autoimmune diseases, including uveitis. However, its impact on the plasma metabolic profile of recurrent autoimmune uveitis remains unclear. This study aims to explore the effect of ART on the plasma metabolic features of recurrent experimental autoimmune uveitis (EAU) in a Lewis rat. : Rats were clinically and pathologically evaluated for the development of recurrent EAU induced by inter-photoreceptor retinoid-binding protein (IRBP) R16 peptide-specific T-cells (tEAU). The disruptive effects of ART on tEAU were investigated to evaluate the potential role of rat recurrent EAU. Differentially expressed metabolites were identified in the plasma of rats by untargeted metabolomics analysis after ART treatment. The differential metabolites were applied to subsequent pathway analysis and biomarker analysis by MetaboAnalyst. : ART can significantly alleviate the severity of clinical signs and pathological injuries of eyeballs with tEAU. Both non-supervised principal component analysis and orthogonal partial least-squares discriminant analysis showed 84 differential metabolites enriched in 16 metabolic pathways in the tEAU group compared with heathy controls and 51 differential metabolites enriched in 17 metabolic pathways, including arginine and proline metabolism, alanine metabolism, and aminoacyl-tRNA biosynthesis, in the ART-treated group compared with the tEAU group. Particularly, upregulated L-alanine levels in both alanine metabolism and aminoacyl-tRNA biosynthesis were associated with T-cell activation, while elevated spermidine and N-acetyl putrescine levels in arginine and proline metabolism related to T-cell differentiation proved to be valuable biomarkers for ART treatment. : Our study demonstrates that ART treatment can alleviate recurrent uveitis by altering the plasma metabolic characteristics associated with T-cell activation and differentiation, which might provide novel insights for potential therapeutic treatments.
由于慢性复发性眼部炎症，确定非感染性葡萄膜炎的有效且安全的治疗方案仍然具有挑战性。先前的研究表明，青蒿琥酯（ART）在包括葡萄膜炎在内的几种经典自身免疫性疾病中发挥免疫抑制作用。然而，其对复发性自身免疫性葡萄膜炎血浆代谢谱的影响仍不清楚。本研究旨在探讨ART对Lewis大鼠复发性实验性自身免疫性葡萄膜炎（EAU）血浆代谢特征的影响。：对大鼠进行临床和病理评估，以观察由光感受器间类视黄醇结合蛋白（IRBP）R16肽特异性T细胞诱导的复发性EAU（tEAU）的发展情况。研究ART对tEAU的破坏作用，以评估大鼠复发性EAU的潜在作用。在ART治疗后，通过非靶向代谢组学分析鉴定大鼠血浆中差异表达的代谢物。利用MetaboAnalyst对差异代谢物进行后续的通路分析和生物标志物分析。：ART可显著减轻tEAU大鼠眼球的临床症状严重程度和病理损伤。非监督主成分分析和正交偏最小二乘判别分析均显示，与健康对照组相比，tEAU组有84种差异代谢物富集于16条代谢通路；与tEAU组相比，ART治疗组有51种差异代谢物富集于17条代谢通路，包括精氨酸和脯氨酸代谢、丙氨酸代谢以及氨酰-tRNA生物合成。特别是，丙氨酸代谢和氨酰-tRNA生物合成中上调的L-丙氨酸水平与T细胞活化相关，而精氨酸和脯氨酸代谢中与T细胞分化相关的亚精胺和N-乙酰腐胺水平升高被证明是ART治疗的有价值生物标志物。：我们的研究表明，ART治疗可通过改变与T细胞活化和分化相关的血浆代谢特征来减轻复发性葡萄膜炎，这可能为潜在的治疗方法提供新的见解。
