超声多模态显像动态监测NF-κB调控溃疡性结肠炎黏膜炎症及黏膜愈合

Ulcerative colitis (UC), usually occurs at an early age, and has a high recurrence rate, thus leading to severe labor loss. Therefore, the increasing incidence rate of ulcerative colitis (UC) has made the disease a huge economic and social burden of the country. The pathogenesis of UC has been proved to have an essential correlation with chronic and relapsing inflammation of mucosa. NF-κB is believed to be one of the most essential pathways that regulate the process of mucosal inflammation and angiogenesis, and the pharmacological blockage of NF-κB activation is a hot spot in the researching field of target therapy. Mucosal healing (MH) may be significantly related to the good prognosis of the patients with UC. Noninvasive imaging modality is the future focus of the MH evaluation. With the development of some sophisticated ultrasound imaging techniques, such as contrast-enhanced ultrasonography and elastography, abdominal ultrasound imaging may have the potential abilities to make quantitative assessments of the mucosal inflammation of UC. .In this research, the regulating mechanism of NF-κB and VEGF-A will be studied at different points in time after establishing the animal models of UC, and further etiology will be learned by performing target blockage of the NF-κB pathway. In the meanwhile, the quantitative assessments of mucosal inflammation and mucosal healing will be made by the multiple ultrasound modality combining grey-scale ultrasound, color-Doppler ultrasound, micro-vascular imaging ultrasound and elastography. Meanwhile, taking the clinical comprehensive assessments of UC as the gold standard, we will investigate the value of multiple ultrasound in the assessment of mucosal inflammation and MH through the follow-up of cases of moderate to severe UC.The results of our study may help to set up an imaging platform of visual and quantitative evaluation of UC inflammatory activity and MH in vivo, as well as guide further research in pathogenesis and clinical translation.

溃疡性结肠炎（UC）在我国的发病率逐年增高，该病青少年期起病、复发率高，造成巨大经济、社会负担。慢性反复炎症导致黏膜损伤是UC发病的中心环节，NF-κB通路调控黏膜炎症、新生血管及其靶向药物已成为研究热点。治疗后黏膜愈合是UC患者预后良好的重要指标，非侵入性的影像学评价黏膜愈合是未来的研究方向。经腹超声在炎性肠病诊治的价值已被广泛认可，而超声造影、超声剪切波弹性显像有望成为定量评估UC的良好技术手段。.本研究拟在UC小鼠模型构建后不同时间点研究NF-κB及VEGF-A调控炎症机制，并靶向阻断NF-κB，进一步探讨病因，同期采用灰阶、微血管显像及剪切波弹性超声定量评估黏膜炎症及黏膜愈合；通过中重度活动期UC临床病例的治疗随访，以临床综合参数为金标准，探究超声定量评价黏膜愈合的临床可行性。研究成果有望为UC炎症活动、修复、疗效随访提供可视化和量化的超声影像研究平台，深化病因研究及临床转化。

溃疡性结肠炎（UC）在我国的发病率逐年增高，该病青少年期起病、复发率高，造成巨大经济、社会负担。慢性反复炎症导致黏膜损伤是UC发病的中心环节，NF-κB通路调控黏膜炎症、新生血管及其靶向药物已成为研究热点。治疗后黏膜愈合是UC患者预后良好的重要指标，非侵入性的影像学评价黏膜愈合研究热点。经腹超声在炎性肠病诊治的价值已被广泛认可，超声造影等新技术为定量评估炎症活动性提供了良好的技术手段。本研究构建了炎性肠病小鼠模型，通过超声动态观察小鼠在炎症早期、高峰期和缓解期的声像图表现；研究设计了靶向NF-κB的超声微泡，通过体外定征及细胞实验证实该微泡可靶向识别炎性细胞，并进一步在炎性肠病小鼠不同病变时期及治疗前后进行了靶向超声造影成像，结果显示超声可量化评估炎性肠病的炎症活动、修复，为深化病因研究及临床转化提供研究平台。达到了项目的预期目标。