EV71感染引起重症手足口病中枢神经系统病变的机制研究

Enteroviruse 71 (EV71) is a major pathogen causing Hand-Foot-Mouth Disease (HFMD) in children. Severe neurological complications in central nervous system (CNS) accompanying the infection often leads to death of children patients, which including encephalitis, aseptic meningitis, and brain stem encephalitis, and fatal pulmonary edema and hemorrhage. Moreover, virus is detected in only 0–5% of CSF samples from patients with neurological disease, suggesting the inflammatory response is the key of EV71 induced-injury of CNS, but the details of the CNS impairment in HFMD still remains unclear. In this study, we plan to investigate the mechanisms of CNS impairment mediated by EV71-induced inflammatory response, based on a neonatal mouse model of EV71-adapted virus strain, from basic to clinic, from in vitro to in vivo research. The study try to illustrate that the infection of EV71 forms viremia in acute phase, activates macrophage, breakdowns the BBB(blood brain barrier), then activates microphage in CNS, resulting in the severe inflammatory impairment, through the CXCL10-CXCR3 pathway. This research provides scientific foundation for further understanding the molecular pathologic mechanisms of EV71 infection and provides possible targets for curing severe cases clinically.

肠道病毒71型（Enteroviruse 71，EV71）是引起儿童手足口病的主要病原，感染后引发严重的中枢神经系统病变，表现为脑膜炎、脑脊髓膜炎等症状甚至死亡，但重症患儿脑脊液中EV71核酸检出率仅0-5%，提示EV71感染后引发的免疫炎症反应可能是重症患儿中枢神经系统损伤的关键，但具体机制尚不清楚。本研究采用EV71感染新生乳鼠造成中枢神经系统病变动物模型为研究基础，采用体内与体外，基础与临床研究相结合的方法，阐明EV71感染后激活外周血巨噬细胞产生炎症因子，进而破坏血脑屏障，活化小胶质细胞，由趋化因子CXCL10及其受体CXCR3介导的免疫炎症级联反应性损伤。本研究结果为EV71感染引起中枢神经系统病理损伤的分子机制提供一定的科学依据。为临床上救治EV71感染致重症神经系统病变患儿提供可能的治疗靶点。

肠道病毒71型（Enteroviruse 71，EV71）是引起儿童手足口病的主要病原体之一，易并发严重的中枢神经系统病疾病，如脑膜炎、脑脊髓膜炎等甚至导致死亡，但重症患儿脑脊液中EV71核酸检出率仅0-5%，提示EV71感染后引发的免疫炎症反应可能是重症患儿中枢神经系统损伤的关键，但具体机制尚不清楚。本研究从流行病学调查、临床症状分析、EV71感染动物模型和细胞实验四个方面入手，采用体内与体外，基础与临床研究相结合的方法，阐明EV71感染后可通过两次病毒血症在多个器官组织中大量增殖复制，并激活外周血免疫细胞产生炎症因子，进而透过血脑屏障进入中枢神经系统，并介导免疫炎症级联反应性损伤。本研究结果为EV71感染引起中枢神经系统病理损伤的分子机制提供一定的科学依据。为临床上救治EV71感染致重症神经系统病变患儿提供可能的治疗靶点。