■探讨重组人血小板生成素(rhTPO)治疗后脓毒症患者内皮细胞损伤标志物和炎症因子的变化,评价rhTPO对临床预后的影响。
■这项回顾性观察性研究涉及2019年1月1日至2022年12月31日在上海总医院重症监护病房住院的脓毒症患者(根据脓毒症3.0诊断)。根据患者是否接受rhTPO分为两组(对照组和rhTPO)。基线信息,临床资料,预后,以及患者的生存状况,以及炎症因子和免疫功能指标。主要监测指标为内皮细胞特异性分子(ESM-1),人肝素结合蛋白(HBP),CD31;次要监测指标为白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α、血管外肺水指数,血小板,抗凝血酶III,纤维蛋白原,和国际标准化比率。我们用腹腔打针脂多糖(LPS)树立脓毒症小鼠模子。将小鼠随机分为四组:生理盐水,LPS,LPS+rhTPO,和LPS+rhTPO+LY294002。采用酶联免疫吸附法测定小鼠血浆指标。
■共84名患者纳入研究。治疗7天后,与第1天相比,rhTPO组的ESM-1下降更明显(中位数=38.6[四分位距,IQR:7.2to67.8]pg/mLvs.中位数=23.0[IQR:-15.7至51.5]pg/mL,P=0.008)。与对照组相比,rhTPO组的HBP和CD31也显着降低(中位数=59.6[IQR:-1.9至91.9]pg/mLvs.中位数=2.4[IQR:-23.2至43.2]pg/mL;中位数=2.4[IQR:0.4至3.5]pg/mLvs.中位数=-0.6[IQR:-2.2至0.8]pg/mL,P<0.001)。与第1天相比,rhTPO组的炎症标志物IL-6和TNF-α下降更明显(中位数=46.0[IQR:15.8至99.1]pg/mLvs.中位数=31.2[IQR:19.7至171.0]pg/mL,P<0.001;中位数=17.2[IQR:6.4至23.2]pg/mLvs.中位数=0.0[IQR:0.0至13.8]pg/mL,P=0.010)。LPS+rhTPO处理的小鼠显示血管血管性血友病因子显著降低(P=0.003),血管内皮生长因子(P=0.002),IL-6(P<0.001),和TNF-α(P<0.001)高于LPS组小鼠。血管内皮细胞损伤因子血管性假血友病因子(P=0.012),血管内皮生长因子(P=0.001),IL-6(P<0.001),TNF-α(P=0.001)通过抑制PI3K/Akt途径显著升高。
■rhTPO减轻脓毒症的内皮损伤和炎症指标,并可能通过PI3K/Akt途径调节脓毒症内皮细胞损伤。
UNASSIGNED: To evaluate the effect of recombinant human
thrombopoietin (rhTPO) on clinical prognosis by exploring changes in endothelial cell injury markers and inflammatory factors in patients with sepsis after treatment with rhTPO.
UNASSIGNED: This retrospective observational study involved patients with sepsis (diagnosed according to Sepsis 3.0) admitted to Shanghai General Hospital intensive care unit from January 1, 2019 to December 31, 2022. Patients were divided into two groups (control and rhTPO) according to whether they received rhTPO. Baseline information, clinical data, prognosis, and survival status of the patients, as well as inflammatory factors and immune function indicators were collected. The main monitoring indicators were endothelial cell-specific molecule (ESM-1), human heparin-binding protein (HBP), and CD31; secondary monitoring indicators were interleukin (IL)-6, tumor necrosis factor (TNF)-α, extravascular lung water index, platelet, antithrombin III, fibrinogen, and international normalized ratio. We used intraperitoneal injection of lipopolysaccharide (LPS) to establish a mouse model of sepsis. Mice were randomly divided into four groups: normal saline, LPS, LPS + rhTPO, and LPS + rhTPO + LY294002. Plasma indicators in mice were measured by enzyme-linked immunosorbent assay.
UNASSIGNED: A total of 84 patients were included in the study. After 7 days of treatment, ESM-1 decreased more significantly in the rhTPO group than in the control group compared with day 1 (median=38.6 [interquartile range, IQR: 7.2 to 67.8] pg/mL vs. median=23.0 [IQR: -15.7 to 51.5] pg/mL, P=0.008). HBP and CD31 also decreased significantly in the rhTPO group compared with the control group (median=59.6 [IQR: -1.9 to 91.9] pg/mL vs. median=2.4 [IQR: -23.2 to 43.2] pg/mL; median=2.4 [IQR: 0.4 to 3.5] pg/mL vs. median=-0.6 [IQR: -2.2 to 0.8] pg/mL, P <0.001). Inflammatory markers IL-6 and TNF-α decreased more significantly in the rhTPO group than in the control group compared with day 1 (median=46.0 [IQR: 15.8 to 99.1] pg/mL vs. median=31.2 [IQR: 19.7 to 171.0] pg/mL, P <0.001; median=17.2 [IQR: 6.4 to 23.2] pg/mL vs. median=0.0 [IQR: 0.0 to 13.8] pg/mL, P=0.010). LPS + rhTPO-treated mice showed significantly lower vascular von Willebrand factor (P=0.003), vascular endothelial growth factor (P=0.002), IL-6 (P <0.001), and TNF-α (P <0.001) than mice in the LPS group. Endothelial cell damage factors vascular von Willebrand factor (P=0.012), vascular endothelial growth factor (P=0.001), IL-6 (P <0.001), and TNF-α (P=0.001) were significantly elevated by inhibiting the PI3K/Akt pathway.
UNASSIGNED: rhTPO alleviates endothelial injury and inflammatory indices in sepsis, and may regulate septic endothelial cell injury through the PI3K/Akt pathway.