SERS分子病理诊断技术动态监测肝硬化大鼠组织成分变化及其与肠道菌群失衡的相关性研究

为寻求快速、高效的病理检测新方法，我们基于表面增强拉曼散射(SERS)快速诊断、动态监测组织分子结构的优势，通过构建肝靶向SERS探针，监测了早期肝纤维化小鼠肝组织细胞中糖类、脂质等成分变化，提出了SERS分子病理诊断的概念。针对目前肠道微生态对肝病发生发展影响机制不明的现状，近期利用SERS分子病理诊断技术监测了早期肝硬化大鼠组织成分变化，发现toll样受体4在早期肝硬化中起重要作用；S1、S2期肝硬化大鼠的组织SERS图谱具有高度一致性且与正常对照组有显著性差异。肠道微生物组学分析结果与之高度吻合。据此，本项目拟采集完整肝硬化分期下大鼠肝组织的SERS图谱，辅以高通量测序，监测病变过程中肠道菌群失衡与SERS图谱的变化，结合传统病理检测、质谱分析、免疫组化等技术，并融合机器学习算法，深入解析“肠道菌群-SERS图谱-肝组织成分”之间相关性及因果关系，建立起肠道菌群与肝病全局监测新方法。

In order to seek a new method for rapid and efficient pathological detection, we constructed a liver-targeted SERS probe to monitor the liver of mice with early hepatic fibrosis based on the advantages of surface-enhanced Raman scattering (SERS) for rapid diagnosis and dynamic monitoring of tissue at the molecular level. The changes of carbohydrates, lipids and other components in cells of liver tissues were monitored, and the concept of SERS molecular pathological diagnosis has been put forward. In view of the current situation that the mechanism of intestinal microecology on the influence and development of liver disease is still unclear, SERS molecular pathological diagnosis technology was used to monitor the changes of tissue components in early-stage liver cirrhosis rats, and it was found that toll-like receptor 4 played an important role in early-stage liver cirrhosis The tissue SERS spectra of S1 and S2 cirrhotic rats were highly consistent and significantly different from that of the normal control group. The results of gut microbiome analysis were in good agreement with these observations. And then, we plan to collect the SERS spectra of rat liver tissues at whole liver cirrhosis stages, supplemented by high-throughput sequencing, to monitor the changes in intestinal flora imbalance and SERS spectra during the process of disease. Combined with traditional pathological detection, mass spectrometry analysis, Immunohistochemistry and other techniques, together with machine learning algorithms, the correlation and causal relationship between "intestinal flora-SERS spectra-liver tissue components" will be deeply analyzed, and a new method for global dynamic monitoring of intestinal flora and liver disease can be thus established.