■弥漫性肺泡出血(DAH)是一种灾难性的临床综合征,是系统性红斑狼疮(SLE)肺部受累的表现之一,以咯血为特征,弥漫性肺浸润,和呼吸衰竭。然而,DAH的治疗选择仍然有限,与DAH相关的研究需要探索更有效的治疗方向,以改善疾病管理和预后.
■本研究利用了前列腺素诱导的DAH小鼠模型来模拟SLE患者DAH的病理过程。进行蛋白质组学分析以检测存活和非存活小鼠血浆中的差异表达蛋白(DEP),其次是生物学功能和途径的分析。然后在有或没有DAH和有或没有致命结局的DAH鼠模型的SLE患者的血浆中证实了最显著的DEP。最后,结合珠蛋白(Hp)替代的治疗价值在DAH小鼠模型中通过肺组织病理学,RT-qPCR,和生存分析。
■这项研究确定了178个DEP,在非存活组中有118个上调和60个下调的DEP。在一组著名的京都基因和基因组百科全书(KEGG)途径中,补体和凝血级联是与DAH过程相关的最突出的途径。稍后,最重要的DEP,触珠蛋白(Hp),通过ELISA测试证实,SLE-DAH和DAH小鼠模型的血浆显着降低,结果较差。最后,与对照组相比,Hp治疗组DAH的严重程度明显减轻,表现为促炎细胞因子(IL-6和TNF-α)水平降低,抗炎细胞因子(IL-10和TGF-β)水平升高,降低死亡率。
■在SLE-DAH中观察到血浆Hp水平降低,Hp替代疗法可以减轻DAH小鼠的肺出血并降低死亡率。这项研究确定了Hp作为其临床诊断和治疗方向的潜在生物标志物。
UNASSIGNED: Diffuse alveolar hemorrhage (DAH) is a catastrophic clinical syndrome and one of the manifestations of pulmonary involvement in systemic lupus erythematosus (SLE), which is characterized by hemoptysis, diffuse pulmonary infiltrates, and respiratory failure. However, the treatment options for DAH remain limited, and DAH-related studies are needed to explore more effective therapeutic directions for better disease management and improved prognosis.
UNASSIGNED: This study utilized the pristane-induced DAH murine model to mimic the pathological process of DAH in patients with SLE. Proteomic analysis was conducted to detect differentially expressed proteins (DEPs) in the plasma of surviving and non-surviving mice, followed by an analysis of biological functions and pathways. The most significant DEP was then confirmed in the plasma of SLE patients with or without DAH and DAH murine model with or without fatal outcomes. Finally, the therapeutic value of
haptoglobin (Hp) replacement was validated in a DAH murine model through lung histopathology, RT-qPCR, and survival analysis.
UNASSIGNED: This study identified 178 DEPs, with 118 upregulated and 60 downregulated DEPs in the non-survival group. Within a set of notable Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, complement and coagulation cascades emerged as the most prominent pathway associated with the process of DAH. Later, the most significant DEP,
haptoglobin (Hp), was confirmed to exhibit a significant decrease in the plasma of individuals with SLE-DAH and DAH murine model with poor outcomes by the ELISA test. Finally, compared with the control group, the severity of DAH in the Hp treatment group was alleviated significantly, as manifested by the decreased levels of pro-inflammatory cytokines (IL-6 and TNF-α), increased levels of anti-inflammatory cytokines (IL-10 and TGF-β), and decreased mortality.
UNASSIGNED: A reduction in plasma Hp levels was observed in SLE-DAH, and the replacement therapy with Hp could alleviate pulmonary hemorrhage and reduce mortality in DAH mice. This study identified Hp as a potential biomarker for its clinical diagnosis and a direction for treatment.