EBF2在腹股沟疝形成及疝修补术后补片感染中的作用及分子机制

Although with a high incidence rate, inguinal hernia with mesh infection, the most common postoperative complication, made its treatment tricky. However, the precise mechanisms are still unknown. Our previous study found that the tolerance of local tissue to infection also execute an important role in mesh infection with bacterial infection of sac after hernia repair patch the main reason behind. We then found a gradually decreased expression of EBF2 in transverse fascia tissues among healthy subjects, inguinal hernia patients and inguinal hernia patients with repair mesh infection by gene-chip. Reduced EBF2 expression lowered PPARγ level, which on the one hand reduced the ratio of collagenⅠ/Ⅲ through elevating (MMP1 and MMP13) expression. On the other hand, EBF2 also could directly activate inflammatory cytokines (IL-6, TNF-α and NF- κB) . In this study, via the cell, animal and clinical experiments, we will for the first time reveal that a decreased EBF2 expression in the transverse fascia reduced cellular PPARγ level which down regulated PPARγ expression. Reduced PPARγ contributed to an overproduced matrix proteases and inflammatory cytokines which eventually lead to a lower collagenⅠ/Ⅲ ratio, a looser collagen fiber structure and a more exacerbated local inflammatory response. Our studies elucidate a novel mechanism underlying inguinal hernia and could possibly provide new method for mesh infection future prevention.

腹股沟疝发病率高，补片感染是其术后常见并发症，但机制并不清楚。我们的前期研究发现，疝囊细菌感染是疝修补术后补片感染的原因之一，但局部组织对感染的耐受性也发挥了重要作用。预实验通过基因芯片技术发现EBF2在健康者、腹股沟疝患者及疝修补术后补片感染患者的腹横筋膜组织中表达量逐渐下降。并且EBF2下调导致PPARγ表达的降低，即可以通过上调基质金素蛋白酶（MMP1及MMP13）表达，降低Ⅰ/Ⅲ型胶原蛋白比例，又可以直接激活炎症因子（IL-6、TNF-α及NF-κB）。本研究将从临床样本、细胞和动物三个层面首次揭示：腹横筋膜内EBF2下降→PPARγ表达降低→基质金素蛋白酶及炎症因子表达量增多→Ⅰ/Ⅲ型胶原蛋白比例下降、胶原纤维结构疏松、局部炎症反应加重→促进腹股沟疝形成及疝修补术后补片感染这一机制，为腹股沟疝形成机制的阐明及疝修补术后补片感染的预防提供新的思路。