基于影像组学技术探讨肠道微生物群对脑出血后血肿周围水肿动态变化的作用机制

脑出血是严重危害人类健康疾病。我们前期研究表明脑出血早期血肿扩大患者多伴有血肿周围水肿（PHE）明显增加，且PHE是影响脑出血预后的重要因素，其机制尚不清楚。最新发现，肠道菌群可通过“肠-脑”轴介导多种神经疾病的免疫炎症反应。然而，肠道菌群是否能调控血肿周围组织免疫炎症反应和PHE的发生发展尚待解决。我们发现小鼠肠道菌群紊乱会导致PHE增加和神经功能损伤加重。我们推测：在肠道菌群紊乱状态下，刺激TLR诱导大量炎症/促炎物质表达，进入中枢后加重血肿周围组织炎症级联反应和水肿生成，继发神经功能损伤。本项目拟用影像组学技术，探究肠道菌群与血肿周围水肿的时空量效应关系。基于粪菌移植技术，构建人源化小鼠模型，以短链脂肪酸（SCFAs）对人源化脑出血模型小鼠进行干预，揭示SCFAs通过JAK/STAT/SOCS通路调控PHE变化的规律。本研究有望从“肠-脑”轴的角度为脑出血诊疗提供新的策略和干预靶点。

Intracerebral hemorrhage (ICH) is a devastating neurological disorder that is associated with heavy health burden. Our previous research suggested that early edema growth is associated with hematoma growth and perihematoma edema (PHE) is associated with poor outcome. However, the underlying mechanism is still unknown. Recently studies suggested that gut microbiome might mediate the immune and inflammatory response of various neurological diseases through the Gut-Brain axis. However, whether gut microbiome can regulate the immune inflammatory response and the development of PHE around hematoma tissues remains unclear. We found that the disturbance of gut microbiome in mice could lead to the increase of PHE and the aggravation of neurological damage. We speculate that gut microbiome disturbance may stimulate TLR induced inflammatory response, aggravating the inflammatory cascade reaction and edema formation in the tissues around the hematoma, resulting in secondary damage. In this project, we intend to explore the temporal and spatial effects of PHE and gut microbiome by using the Radiomics method. Based on fecal microbiota transplantation, the humanized mouse model was constructed, and the short-chain fatty acids (SCFAs) were used to intervene the ICH model mice, revealing the regulation of SCFAs regulating the change of PHE through JAK/ STAT / SOCS pathway. The results of this study are expected to provide new strategies and intervention targets for the diagnosis and treatment of intracerebral hemorrhage from the perspective of Gut-Brain axis.