Tissue plasminogen activator (tPA) is a serine protease involved in cleavage of neurotrophic factors. In addition, tPA and neuroserpin can also directly bind to low density lipoprotein receptor-related protein 1 (LRP1), promoting neurogenesis and neurite outgrowth. Given both the cleavage and non-cleavage actions of the fibrinolytic system are crucial in neurological functions, the present study, for the first time, systematically detected the changes of fibrinolytic system factors in rats exposed to chronic unpredictable mild stress (CUMS) or lipopolysaccharide (LPS) and patients with depression. In general, our data demonstrated that both CUMS and LPS reduced tPA but elevated plasminogen activator inhibitor-1 (PAI-1; SERPINE1) mRNA expression. Intriguingly, decreased expression of neuroserpin and LRP1 was also observed in rats exposed to CUMS or LPS. The down-regulated neuroserpin and LRP1 signaling were confirmed by western blotting and immunoflurence data. Likewise, elevated PAI-1 but a significant reduction of neuroserpin and LRP1 mRNA expression were observed in the peripheral blood mononuclear cells (PBMCs) of patients with first-episode depression, and the mRNA levels of PAI-1, neuroserpin and LRP1 were correlated with the Beck Depression inventory (BDI) scores, further strengthening the clinical significance and involvement of the fibrinolytic system in depression. Collectively, the present study demonstrated the alterations of fibrinolytic system in stressed and inflamed brain and in patients with first-episode depression, firstly showing that not only the cleavage actions, but also the non-cleavage actions of the system may play an essential role in the development of depression.

组织纤溶酶原激活剂（tPA）是一种丝氨酸蛋白酶，参与神经营养因子的切割。此外，tPA和Neuroserpin还可以直接与低密度脂蛋白受体相关蛋白1（LRP1）结合，从而促进神经发生和神经突生长。鉴于纤维蛋白溶解系统的裂解和非裂解作用在神经功能中均至关重要，因此本研究首次系统地检测了暴露于慢性不可预测的轻度应激（CUMS）或脂多糖的大鼠中纤维蛋白溶解系统因子的变化（ LPS）和抑郁症患者。通常，我们的数据表明CUMS和LPS均可降低tPA，但可提高纤溶酶原激活物抑制剂1（PAI-1; SERPINE1）mRNA表达。有趣的是 在暴露于CUMS或LPS的大鼠中也观察到神经丝氨酸蛋白酶抑制剂和LRP1的表达降低。免疫印迹和免疫印迹数据证实了神经丝氨酸蛋白酶抑制剂和LRP1信号的下调。同样，在首发抑郁症患者的外周血单个核细胞（PBMC）中，PAI-1升高，但神经丝氨酸蛋白酶抑制剂和LRP1 mRNA表达显着降低，并且PAI-1，神经丝氨酸蛋白酶抑制剂和LRP1的mRNA水平与贝克抑郁量表（BDI）评分，进一步增强了纤溶系统在抑郁症中的临床意义和参与度。总体而言，本研究证明了紧张和发炎的大脑以及首发抑郁症患者的纤溶系统发生了变化，首先表明不仅裂解作用，