Honokiol预防术后腹腔粘连的机制探索：抑制依赖于TGFβ1-SMAD2/3通路活化的腹膜间皮细胞间充质转分化

腹腔粘连始于间皮损伤。而间皮-间充质转分化(MMT)是损伤诱导腹膜纤维化的基础，在腹腔粘连中亦或重要。我们通过生信预测TGFβ1-Smad2/3通路活化诱导间皮MMT可能是腹腔粘连的关键步骤。前期实验发现小分子Honokiol可预防腹腔粘连，促进LKB1表达抑制Smad3磷酸化，逆转受损腹膜间皮MMT。故我们推测：(1)依赖于TGFβ1-Smad2/3通路活化的间皮MMT，是腹腔粘连的关键环节；(2)Honokiol通过上调LKB1表达抑制TGFβ1-Smad2/3通路激活，导致间皮MMT受阻，以此预防腹腔粘连。为证实该假说，我们以生信预测为线索，在临床标本、细胞、组织培养、动物四个层次，采用激光共聚焦、分子生物学、3D细胞培养、细胞示踪、电镜等技术，解析依赖于TGFβ1-Smad2/3通路的间皮MMT在粘连中的作用，探究Honokiol抑制粘连的机制，为预防腹腔粘连提供新依据和思路。

Postoperative intra-abdominal adhesion begins with mesothelial injury and its mechanism remains unclarified. Mesothelial-to-Mesenchymal Transition (MMT) is the basis of injury-induced peritoneal fibrosis and may play an important role in intra-abdominal adhesion. According to bioinformatic prediction, activation of TGFβ1-smad2/3 pathway to induce MMT may be a key step in intra-abdominal adhesion. Previous experiments found that Honokiol can prevent intra-abdominal adhesion, promote LKB1 expression, inhibit Smad3 phosphorylation and reverse the damage of peritoneal mesothelium MMT. Therefore, we hypothesized that (1) mesothelium MMT, which depends on the activation of TGFβ1-smad2/3 pathway, is the key link of intra-abdominal adhesion; (2) Honokiol inhibits the activation of TGFβ1-smad2/3 pathway by up-regulating the expression of LKB1, leading to the obstruction of MMT in the mesothelium and finally plays a role in preventing intra-abdominal adhesion. In order to verify the hypothesis, taking bioinformatic prediction as clues, clinical specimens, cells culture, tissue culture and animals would be used. A variety of technology will be conducted, such as laser confocal, molecular biology, 3D cell culture, cell lineage tracer, electron microscopy techniques. This research will help us understand the role of TGFβ1-Smad2/3 pathway-dependent MMT in adhesion, explore the mechanism of how Honokiol inhibits adhesion and provide theory basis and new idea for intra-abdominal adhesion prevention.