诊断学理论与实践 ›› 2025, Vol. 24 ›› Issue (06): 583-592.doi: 10.16150/j.1671-2870.2025.06.003
收稿日期:2025-10-10
修回日期:2025-11-20
出版日期:2025-12-25
发布日期:2025-12-25
通讯作者:
黄曼 E-mail: huangman@zju.edu.cn基金资助:Received:2025-10-10
Revised:2025-11-20
Published:2025-12-25
Online:2025-12-25
摘要:
脓毒症在全球范围内每年导致约1 100万例患者死亡,当前发病率仍呈上升趋势,特别是在老龄化社会中。老年患者由于基础疾病多、免疫功能下降,常在感染后迅速演变为脓毒症,预后较差。此外,器官移植、恶性肿瘤等免疫抑制患者,脓毒症的发生率也显著高于一般人群。2017年至2019年,我国住院患者脓毒症年标准化发病率为(328.25~421.85)/10万,其中超过57%的病例发生在65岁以上的老年人。脓毒症作为一种由感染引起全身性过度炎症反应导致的器官功能障碍综合征,仍然是全球范围内导致高死亡率和医疗负担的重要疾病。尽管近年来随着对脓毒症机制的深入研究,其诊断和治疗策略持续完善,但临床实践仍面临三大核心挑战:早期诊断困难,现有评估体系与生物标志物存在局限;抗生素耐药性日益严峻,显著限制治疗选择;疾病极高的异质性导致标准化治疗方案疗效不佳,个体化治疗远未普及。近年,诊断层面新型生物标志物、分子诊断技术与人工智能的应用,正推动早期识别与精准分型能力的革新;在治疗层面,个体化与精准医疗理念日益深入,免疫调节等新型治疗策略展现出应对疾病复杂性的巨大潜力。应对上述三大核心挑战的关键在于将精准医学理念贯穿诊疗全程:通过整合多组学数据深化对疾病异质性的理解,利用前沿技术实现精准诊断与分型,并在此基础上发展靶向治疗,最终实现改善患者预后的目标。
中图分类号:
黄曼, 丁朔. 脓毒症的诊治现状及挑战[J]. 诊断学理论与实践, 2025, 24(06): 583-592.
HUANG Man, DING Shuo. Current status and challenges in sepsis diagnosis and treatment[J]. Journal of Diagnostics Concepts & Practice, 2025, 24(06): 583-592.
表1
脓毒症常用生物标志物比较
| 标志物 | 分泌来源 | 动态变化 | 参考范围 | 特征 |
|---|---|---|---|---|
| 白细胞计数 | 骨髓 | 感染后8~20 h内开始上升,24~48 h内达到峰值,约3 d后恢复至参考范围 | 4 000~12 000 个/mm3 | 细胞因子驱动白细胞的产生和释放,导致其在脓毒症中计数升高;灵敏度59.5%,特异度79.6% |
| PCT | 甲状腺 | 炎症发生后2~4 h内上升,24 h达到峰值,增加数百倍甚至数千倍 | < 0.1 ng/mL | 脓毒症患者中PCT水平升高,与生存率相关,可作为感染严重程度和预后相关生物标志物;灵敏度71%~100%,特异度61%~88% |
| CRP | 肝脏 | 炎症发生后4~6 h内开始上升,在48~72 h达到峰值,炎症刺激消退后24 h内下降 | 0.3~1.0 mg/dL | 由肝脏合成,对炎症刺激反应敏感;灵敏度75%~91%,特异度36%~67% |
| IL-6 | 巨噬细胞和淋巴细胞 | 炎症发生1~2 h内上升,随后在炎症消退过程中缓慢下降 | 5~15 pg/mL | IL-6可激活B和T淋巴细胞,在损伤部位淋巴细胞和巨噬细胞的聚集过程中发挥作用,与疾病严重程度相关;灵敏度68%~72%,特异度72%~73% |
| TNF-α | 巨噬细胞 | 感染后6~8 h内上升 | ≤5 pg/mL | TNF-α是脓毒症中的关键细胞因子,可激活内皮细胞、招募中性粒细胞并调节免疫反应,其水平升高与炎症和器官损伤相关,有助于预后判断;灵敏度82.6%,特异度91.7% |
| 血浆可溶性白细胞分化抗原14亚型 | 巨噬细胞 | 细菌感染后2 h内上升 | <100 pg/mL | 是CD14的可溶性形式,表达于巨噬细胞和单核细胞上,对脂多糖等细菌配体具高亲和力;水平较高可能指示革兰氏阴性细菌感染,有助于评估脓毒症的严重程度和进展;灵敏度77%~85%,特异度73%~88% |
| 可溶髓系细胞表达的触发受体1(sTREM-1) | 中性粒细胞 | - | 31.25~2 000 pg/mL | 是一种表达于中性粒细胞、成熟单核细胞和巨噬细胞表面的糖蛋白,细菌感染可导致sTREM-1表达增加;目前已被研究用于区分细菌感染与非感染性炎症状态及指导脓毒症抗生素治疗;灵敏度73%~89%,特异度74%~86% |
| CD64 | 中性粒细胞 | 感染后48 h内上升 | <1.00 ng/mL | CD64是免疫球蛋白G Fc段的Ⅰ型受体,持续表达于单核细胞、巨噬细胞和树突状细胞表面,并介导细菌吞噬作用;灵敏度87%,特异度89% |
| 高迁移率族蛋白B1 | 巨噬细胞 | - | ≤4 ng/mL | 可由活化的巨噬细胞分泌,或在细胞坏死和凋亡过程中释放,作为一种损伤相关分子模式,通过Toll样受体4和晚期糖基化终末产物受体途径激活巨噬细胞,从而延长炎症反应;灵敏度75.8%,特异度41.3% |
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