PDGF-BB@TiO2纳米管通过PDGFR-β/miR-143-3p/PTEN途径调控高糖环境下种植体周巨噬细胞极化的机制研究

高糖诱导巨噬细胞持续M1极化介导的慢性炎症反应是影响II型糖尿病患者种植体骨愈合障碍的关键原因。前期研究发现将血小板衍生生长因子BB（PDGF-BB）加载至TiO2纳米管表面可诱导高糖条件下巨噬细胞M2极化、改善炎症反应，但具体机制不明。细胞膜表面受体是介导细胞感受外源刺激、调控胞内信号传导的重要媒介；PDGF-BB@TiO2可磷酸化激活M1型巨噬细胞膜表面的β型受体（PDGFR-β），并诱导胞内miR-143-3p表达上调，而阻断受体后巨噬细胞M2极化减弱。因此我们推测，PDGFR-β是调控糖尿病巨噬细胞M2极化的重要靶点。本项目拟利用细胞分生、动物模型等手段阐明PDGF-BB@TiO2通过PDGFR-β介导的miR-143-3p/PTEN途径调控糖尿病种植体周巨噬细胞M2极化的新机制，为研究膜受体介导的细胞功能调控提供理论依据，也为针对II型糖尿病患者的种植体表面优化设计提供新思路。

The chronic inflammatory response mediated by continuous M1 polarized macrophages which induced by high glucose stimulation is the key factor affecting the defect of implant bone healing in patients with type II diabetes mellitus. Previous studies have found that loading platelet-derived growth factor BB (PDGF-BB) on the surface of TiO2 nanotubes can induce M2 polarization of macrophages and improve the inflammatory response under high glucose environment, but the specific mechanism is unclear. Cytomembrane surface receptors are important mediators to mediate the exogenous stimuli and regulate the intracellular signal transduction. PDGF-BB@TiO2 nanotubes can phosphorylate and activate the β-receptor of PDGF (PDGFR-β) on the cytomembrane surface of M1 macrophages, thus inducing the up-regulation of intracellular miR-143-3p expression; while the M2 polarization of macrophages is weakened after blocking PDGFR-β. Therefore, we hypothesized that PDGFR-β is an important target of regulating M2 polarization in diabetic macrophages. This project intends to use cytobiological and molecular biological medthods, animal models and other means to clarify the new mechanism of PDGF-BB@TiO2 nanotubes regulating M2 polarization of diabetic peri-implant macrophages through the miR-143-3p/PTEN pathway mediated by PDGFR-β, so as to provide a theoretical basis for the study of cytomembrane receptor-mediated cell function regulation, and also provide a new idea for the optimization design of implant surface in patients with type II diabetes mellitus.