Sinos Georgios, Schizas Dimitrios, Kapelouzou Alkistis, Frountzas Maximos, Katsimpoulas Michalis, Mylonas Konstantinos S, Kapetanakis Emmanouil I, Papalampros Alexandros, Liakakos Theodore, Alexandrou Andreas
First Department of Surgery, National and Kapodistrian University of Athens, "Laikon" General Hospital, 115 27 Athens, Greece.
Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 115 27 Athens, Greece.
Int J Mol Sci. 2025 Mar 4;26(5):2274. doi: 10.3390/ijms26052274.
Sepsis is a leading cause of death in hospitalized patients. The underlying pathophysiologic mechanisms of sepsis have not been fully elucidated thus far. The receptor of programmed cell death 1 (PD-1) and its ligand (PD-L1), in combination with the Toll-like receptors (TLRs), seem to contribute considerably in systematic responses during sepsis. Investigating the relationship between them and identifying potential target pathways is important in the future management of sepsis, especially in relation to acute lung injury. This study investigated the interactions between TLR-5, -6, and -9 and PD-1/PD-L1 expression in a septic mouse model. Sixty C57BL/6J mice were included and categorized in six study groups. Three sepsis (S) groups (24 h, 48 h, and 72 h) and three sham (Sh) groups (24 h, 48 h, and 72 h) were created. Cecal ligation and puncture (CLP) was utilized to simulate sepsis in the S groups. Hematological analysis and lung tissue histopathological analysis were performed after 24 h, 48 h, and 72 h. Significant decreases in S groups compared to Sh groups in WBC and lymphocyte counts at 24, 48, and 72 h were observed. Significant increases in S groups compared to Sh groups in RBC and monocyte counts, IL-6 and IL-10 levels, alveolar flooding, and alveolar collapse were demonstrated by histopathological analysis. This study suggested a strong correlation between TLR expression and PD-1/PD-L1 up-regulation in lung tissue during sepsis. These molecules, also, seem to contribute to the histopathological changes in lung tissue during sepsis, leading to acute lung injury.
脓毒症是住院患者死亡的主要原因。迄今为止，脓毒症的潜在病理生理机制尚未完全阐明。程序性细胞死亡蛋白1（PD-1）及其配体（PD-L1），与Toll样受体（TLR）共同作用，似乎在脓毒症期间的全身反应中发挥了重要作用。研究它们之间的关系并确定潜在的靶标途径对于脓毒症的未来治疗很重要，尤其是与急性肺损伤相关的治疗。本研究在脓毒症小鼠模型中研究了TLR-5、-6和-9与PD-1/PD-L1表达之间的相互作用。纳入60只C57BL/6J小鼠并分为六个研究组。创建了三个脓毒症（S）组（24小时、48小时和72小时）和三个假手术（Sh）组（24小时、48小时和72小时）。在S组中采用盲肠结扎和穿刺（CLP）来模拟脓毒症。在24小时、48小时和72小时后进行血液学分析和肺组织病理组织学分析。观察到在24、48和72小时时，S组的白细胞和淋巴细胞计数与Sh组相比显著降低。组织病理学分析显示，S组的红细胞和单核细胞计数、IL-6和IL-10水平、肺泡积水和肺泡塌陷与Sh组相比显著增加。本研究表明，脓毒症期间肺组织中TLR表达与PD-1/PD-L1上调之间存在密切相关性。这些分子似乎也促成了脓毒症期间肺组织的组织病理学变化，导致急性肺损伤。
