基于超声影像方法研究肠道菌群与甲状腺VEGF表达的联合干预对改善桥本甲状腺炎的作用

研究表明肠道菌群与甲状腺VEGF表达均可影响甲状腺功能和免疫炎症，但干预它们对改善桥本甲状腺炎(HT)的效果和作用尚不清楚。在前期研究中，我们发现HT患者双歧杆菌属和乳杆菌属明显减少，血液VEGF水平显著升高，HT大鼠血液VEGF水平和甲状腺VEGF表达水平也明显升高。基于此，我们提出双歧杆菌属和乳杆菌属的某些特征菌种减少和甲状腺VEGF表达升高共同影响甲状腺功能并加重其炎症浸润，从而参与HT的发生发展。本研究将肠道菌群干预与超声靶向微泡破裂(UTMD)介导的甲状腺VEGF表达干预相结合，利用超声影像学、微生物学、生物化学与分子生物学等手段，从人群和动物两个层面，兼顾甲状腺形态/组织硬度/血流/炎性反应与肠道菌群和VEGF表达的交互效应，拟围绕肠道菌群与UTMD介导的甲状腺VEGF表达的联合干预对改善HT的效果进行研究，阐明其在改善甲状腺功能和免疫炎症中的作用，为HT的早期防治提供新思路。

Previous studies suggested that alteration of gut microbiota and changes in VEGF expression in thyroid gland would affect thyroid function and its immune inflammation, but the effects of regulating them on improving Hashimoto's thyroiditis (HT) remain unknown. In previous experiments, we identified that Bifidobacterium and Lactobacillus genera in HT patients were significantly reduced, blood VEGF levels in HT patients were significantly increased, and blood VEGF levels and thyroid VEGF expression levels in HT rats were also significantly increased. Based on the pre-experimental results of populations and animals, we propose that the reduction of certain specific species of Bifidobacterium and Lactobacillus genera in gut microbiota and the increased expression of VEGF in the thyroid gland would affect the thyroid function and increase its inflammatory infiltration, thereby participating in the development of HT. The proposal will first analyze gut microbiota and VEGF levels in strictly matched case-control samples to identify the specific species in Bifidobacterium and Lactobacillus genera and the changes in VEGF levels. Then, the correlation analyses of thyroid morphology, blood flow, tissue hardness, and function will be performed between each subgroup of HT patients and between them and healthy control group, in order to determine the relationships between specific species, VEGF levels, thyroid morphology, blood flow, tissue hardness, and function. Finally, the innovative joint interventions of specific species in gut microbiota and VEGF expression mediated by ultrasound-targeted-microbubble-destruction (UTMD) in thyroid gland would be conducted in HT rats. Based on three aspects in thyroid (thyroid morphology / blood flow / tissue hardness and thyroid function and thyroid inflammatory), together with the interactive associations of them with specific species in gut microbiota and VEGF expression, the effects of joint interventions of specific species in gut microbiota and VEGF expression mediated by UTMD in thyroid gland on improving HT would be verified. These will clarify their roles in improving thyroid function and immune inflammation levels, and provide new methods and new ideas for the early prevention and treatment of HT.