卒中后肺炎致多种非肺炎并发症风险增加的细胞及分子机制研究

Medical complications are common among stroke patients during acute hospitalization. Evidences showed that these medical complications not only increase length of hospital stay and medical cost, but also are major causes of mortality and morbidity after stroke. Although several studies have systematically investigated medical complication(s) after stroke, much attention was paid to specific complication(s) and nearly no study was focused on investigating potential interrelationship among them. In daily clinical practice, it is common for stroke patients to experience multiple medical complications (>2) during acute hospitalization, especially for those patients with severe neurological deficit. It is still unclear whether these stroke-associated medical complications occur independently or not? And if not, what is the potential association among them? Based on the largest stroke registry in China, the China National Stroke Registry (CNSR), we systematically investigated interrelationship among common medical complications after acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH). It was found that the combination of common medical complications after acute stroke was not random and pneumonia was significantly associated with the development of several non-pneumonia medical complications (such as gastrointestinal bleeding, decubitus ulcer, deep vein thrombosis, epileptic seizure, atrial fibrillation/flutter, urinary tract infection, and recurrent stroke) after both AIS and ICH. Organ crosstalk is an emerging, interesting and clinically relevant field. Currently, limited is known about the intrinsic pathway and pathophysiological mechanisms of medical complications crosstalk after acute stroke. Accumulating evidence indicated that acute stroke could induce significant immunological changes, such as stroke-induced immunodepression, which was a key facilitating factor for poststroke infection, especially pneumonia. Meanwhile, we can learn important lessons from studies on postinjury multiple organ dysfunction syndrome (MODS), in which pneumonia or acute lung injury has been described as the pacemaker of multiple organ failure and could induce MODS by releasing inflammatory mediators into bloodstream. Based on these indirect evidences, we speculated that association between pneumonia and development of non-pneumonia medical complications after acute stroke might be medicated by systemic immunological response and inflammatory mediators. In the present study, we aim to further investigate the potential cellular and molecular mechanisms underlying multiple medical complications after acute stroke by observing the dynamic changes of peripheral blood white blood cell, cytokines and microRNAs. Our study would encourage studies to clarify pathophysiological mechanisms underlying interrelationship among stroke-associated medical complications, as hopefully would pave ways to develop novel preventive strategies for improving stroke outcome.

卒中后并发症是一种常见的临床现象，不仅增加了患者住院时间和医疗费用，而且大大增加了死亡和残疾的风险。虽然国际上有多个卒中并发症的相关研究，但他们更多的关注了对单个、特定并发症发生特征的研究，而大大忽略了对各并发症之间潜在关系的探索。近期，我们在国际上首次报道了"急性卒中后肺炎是增加其他多种非肺炎并发症发生风险的重要危险因素"，并提出"卒中后肺炎至其他非肺炎并发症发生风险增加的三步曲理论假设"。在此次立项中，我们拟基于前期已建立的急性卒中住院并发症前瞻性队列，通过监测卒中患者外周血白细胞（分类、免疫分型和数量）、炎症介质（种类和数量）和microRNAs（种类和数量）的动态变化，揭示卒中后肺炎致其他非肺炎并发症风险增加的潜在细胞及分子机制。对卒中后并发症相互关系病生机制的研究，不仅有利于我们深入认识卒中后并发症发生发展的规律，更为我们从整体角度探索卒中后各种并发症有效的防控策略开辟崭新的领域

卒中后并发症是一种常见的临床现象，不仅增加了患者住院时间和医疗费用，而且大大增加了死亡和残疾的风险。虽然国际上有多个卒中并发症的相关研究，但他们更多的关注了对单个、特定并发症发生特征的研究，而大大忽略了对各并发症之间潜在关系的探索。在此次立项中，我们拟基于前期已建立的急性卒中住院并发症前瞻性队列，通过监测卒中患者外周血白细胞（分类、免疫分型和数量）、炎症介质（种类和数量）和microRNAs（种类和数量）的动态变化，揭示卒中后肺炎致其他非肺炎并发症风险增加的潜在细胞及分子机制。我们建立了卒中并发症临床预测模型、并对卒中后肺炎、深静脉血栓、上消化道出血等进行比对，且揭示相关分子机制。为日后的临床工作提供便利，并为后续的相关研究打下夯实基础。