酪酸梭菌介导MMP9调控重症胰腺炎并腹腔内高压肠上皮屏障的机制研究

重症胰腺炎（SAP）因病情进展快且易并发腹腔内高压（IAH）和死亡率高而受广泛关注，但迄今仍缺乏有效防治方案。我们前期发现SAP并IAH模型大鼠酪酸梭菌减少及肠屏障结构破坏，给予酪酸梭菌可明显上调肠上皮紧密连接蛋白表达和肠道共生菌丰度；进一步研究还发现给予酪酸梭菌治疗的模型大鼠MMP9表达明显降低，然而酪酸梭菌可否调控肠上皮屏障，如何调控等关键问题均未解决。本项目拟SAP并IAH患者为切入点，构建SAP并IAH大鼠模型及细胞炎症模型，采用酪酸梭菌干预，CRISPR/Cas9技术和屏障功能检测等方法阐明酪酸梭菌抗炎调控机制：酪酸梭菌对SAP并IAH肠屏障的影响；酪酸梭菌介导MMP9维护SAP并IAH肠屏障的机制，探索“酪酸梭菌经MMP9调控肠屏障结构和功能，进而改善肠道炎症损伤及肠屏障功能、减缓SAP并IAH进程”等科学问题，为酪酸梭菌抗炎调控机制提供新理论，为SAP防治奠定理论和实验基础。

Severe acute pancreatitis(SAP) is received extensively attention because of its speedy development, high mortality and being prone to complicated by intra-abdominal hypertension, however, there is still a lack of effective therapeutic targets and control programs. Our early research observed that the abundance of clostridium butyricum was obviously reduced and the intestinal barrier structure was harmed in SAP rats mode. If the rats were offered with C. butyricum, the expression of intestinal epithelium tight junction protein and the abundance of symbiotic bacteria were markedly increased, furtherly, we found that the expression of MMP9 was decreased significantly. However, there is still no solution to the critical problem of that if clostridium butyricum is involved in regulation of intestinal barrier and how to regulate. Taking clinical SAP with IAH patients as a base and building rats model of SAP with IAH and inflammatory cell, the study will adopt clostridium butyricum intervention, CRISPR/Cas9 technology and detection of intestinal barrier function to research the mechanism of anti-inflammation and mediation of clostridium butyricum, the influence of clostridium butyricum to intestinal mucosal barrier of SAP with IAH and the mechanism of clostridium butyricum defending the intestinal mucosal intestinal by mediating MMP9. The study is to explore the scientific problems, which is that clostridium butyricum regulates structure and function of intestinal mucosal barrier via mediating MMP9 to ameliorate the intestinal inflammation and intestinal barrier and slow down the progress of SAP with IAH, for providing the theoretical guidance for clostridium butyricum anti-inflammatory and regulatory mechanism and establishing the theory and experimental base for the prevention and treatment of SAP.