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脓毒症和脓毒性休克患者中Nox2活性与血小板活化之间的相互作用:一项前瞻性研究。

Interplay between Nox2 Activity and Platelet Activation in Patients with Sepsis and Septic Shock: A Prospective Study.

作者信息

Tiseo Giusy, Cavarretta Elena, Forniti Arianna, Nocella Cristina, Sciarretta Sebastiano, Spagnolello Ornella, Baldini Enrico, Peruzzi Mariangela, Bertazzoni Giuliano, Menichetti Francesco, Marullo Antonino G M, Miraldi Fabio, Morelli Andrea, Frati Giacomo, Carnevale Roberto, Marco Falcone

机构信息

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Mediterranea Cardiocentro, Napoli, Italy.

出版信息

Oxid Med Cell Longev. 2020 Oct 27;2020:4165358. doi: 10.1155/2020/4165358. eCollection 2020.

Abstract

BACKGROUND

Although preclinical studies highlighted the potential role of NADPH oxidase (NOX) in sepsis, only few studies evaluated the oxidative stress in patients with sepsis and septic shock. The objective of the study is to appraise the oxidative stress status and platelet function in patients with sepsis and septic shock compared to healthy controls.

METHODS AND RESULTS

Patients with sepsis or septic shock admitted to the hospital Policlinico Umberto I (Sapienza University, Rome) underwent a blood sample collection within 1 hour from admission. Platelet aggregation, serum thromboxane B2 (TxB2), soluble NOX2-derived peptides (sNox2-dp), and hydrogen peroxide breakdown activity (HBA) were measured and compared to those of healthy volunteers. Overall, 33 patients were enrolled; of these, 20 (60.6%) had sepsis and 13 (39.4%) septic shock. Compared to healthy controls ( = 10, age 67.8 ± 3.2, male 50%), patients with sepsis and septic shock had higher platelet aggregation (49% (IQR 45-55), 60% (55.75-67.25), and 73% (IQR 69-80), respectively, < 0.001), higher serum TxB2 (77.5 (56.5-86.25), 122.5 (114-131.5), and 210 (195-230) pmol/L, respectively, < 0.001), higher sNox2-dp (10 (7.75-12), 19.5 (17.25-21), and 33 (29.5-39) pg/mL, respectively, < 0.001), and lower HBA (75% (67.25-81.5), 50% (45-54.75), and 27% (21.5-32.5), respectively, < 0.001). Although not statistically significant, a trend in higher levels of serum TxB2 and sNox2-dp in patients who died was observed.

CONCLUSIONS

Patients with septic shock exhibit higher Nox2 activity and platelet activation than patients with sepsis. These insights joined to better knowledge of these mechanisms could guide the identification of future prognostic biomarkers and new therapeutic strategies in the scenario of septic shock.

摘要

背景

尽管临床前研究强调了烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NOX)在脓毒症中的潜在作用,但仅有少数研究评估了脓毒症和脓毒性休克患者的氧化应激情况。本研究的目的是评估脓毒症和脓毒性休克患者与健康对照者相比的氧化应激状态和血小板功能。

方法与结果

入住罗马萨皮恩扎大学翁贝托一世综合医院的脓毒症或脓毒性休克患者在入院后1小时内接受血样采集。检测血小板聚集、血清血栓素B2(TxB2)、可溶性NOX2衍生肽(sNox2-dp)和过氧化氢分解活性(HBA),并与健康志愿者进行比较。总共纳入了33例患者;其中,20例(60.6%)患有脓毒症,13例(39.4%)患有脓毒性休克。与健康对照者(n = 10,年龄67.8±3.2,男性占50%)相比,脓毒症和脓毒性休克患者的血小板聚集率更高(分别为49%(四分位间距45 - 55)、60%(55.75 - 67.25)和73%(四分位间距69 - 80),P < 0.001),血清TxB2水平更高(分别为77.5(56.5 - 86.25)、122.5(114 - 131.5)和210(195 - 230)pmol/L,P < 0.001),sNox2-dp水平更高(分别为10(7.75 - 12)、19.5(17.25 - 21)和33(29.5 - 39)pg/mL,P < 0.001),而HBA更低(分别为75%(67.25 - 81.5)、50%(45 - 54.75)和27%(21.5 - 32.5),P < 0.001)。虽然无统计学意义,但观察到死亡患者的血清TxB2和sNox2-dp水平有升高趋势。

结论

脓毒性休克患者比脓毒症患者表现出更高的Nox2活性和血小板活化。这些见解以及对这些机制的更好了解可指导在脓毒性休克情况下识别未来的预后生物标志物和新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1de6/7641261/675a91908122/OMCL2020-4165358.001.jpg

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