PDGF-BB-LDH纳米载药PLCL/Pluronic在糖尿病创面愈合中的作用及分子机制

Non-healing wounds represent a common complication of diabetes. Recently, tissue engineering technique is of great concern in the field of repairing diabetic wounds. Different from diabetic foot with vascular stenosis caused by thickening the basement membrane, diabetic wounds exhibit decreases in both angiogenic response and formation of stable epidermis within the wound. The modulation of VEGF-Notch signaling and PI3K-Akt pathway by PDGF plays a crucial role in angiogenesis and cell survival, which seems a promising therapeautic target for diabetes wounds. Our previous study has demonstrated that adipose-derived mesenchymal stem cells combined with PLCL/Pluronic electrospun scaffold could enhance wound healing in SD rats. In this study, we will fabricate PDGF-BB-LDH PLCL/pluronic and evaluate the effect in diabetic wound healing. Subsequently, the controlled release mechanism of PDGF-BB loaded PLCL/Pluronic will be further studied for improving the long-term efficacy of scaffold. In addition, the expression of PDGF-BB、VEGF-Notch signaling and PI3K-Akt pathway related factors in the process of healing will be analyzed to explore the molecular mechanism of diabetic wound healing. Finally, the effects of PDGF-BB over-expression or inhibition in ADSCs on the VEGF-Notch signaling and PI3K-Akt pathway will be fully investigated to clarify the molecular mechanism of vascularization and epidermization in the process of diabetic wound healing, which could be the basement for clinical applications.

创面难愈是糖尿病常见并发症之一，近年来组织工程技术修复糖尿病创面颇受关注。与糖尿病足微血管病变不同，糖尿病创面存在血管化及表皮形成障碍。PDGF调控VEGF-Notch信号通路促进血管新生，调控PI3K-Akt信号通路维持细胞生存和抗凋亡，加速血管和表皮形成，可成为治疗糖尿病创面的新方法。本研究拟构建PDGF-BB-LDH纳米载药PLCL/Pluronic静电纺薄膜用于糖尿病创面的修复，研究PDGF-BB在PLCL/Pluronic中的缓控释机制，为材料的改良提供依据。然后进一步研究糖尿病创面修复中PDGF-BB和血管新生VEGF-Notch信号通路及促有丝分裂PI3K-Akt信号通路相关因子的表达情况，探讨其修复糖尿病创面的可行性。最后，建立PDGF-BB在ADSCs高表达与VEGF-Notch及PI3K-Akt通路的关系，阐明PDGF-BB调控血管化及表皮形成促进糖尿病创面愈合的分子机制，为将来临床应用提供理论基础。

创面难愈是糖尿病常见并发症之一，近年来组织工程技术修复糖尿病创面颇受关注。与糖尿病足微血管病变不同，糖尿病创面存在血管化及表皮形成障碍。PDGF调控VEGF-Notch信号通路促进血管新生，调控PI3K-Akt信号通路维持细胞生存和抗凋亡，加速血管和表皮形成，可成为治疗糖尿病创面的新方法。本研究成功构建了PDGF-BB-LDH纳米载药PLCL/Pluronic静电纺薄膜，并进一步研究糖尿病创面的修复的体内实验和转染后ADSCs的VEGF-Notch及PI3K-Akt通路。结果表明，PDGF-BB-LDH纳米载药PLCL/Pluronic静电纺丝薄膜能够高效地促进糖尿病创面的愈合；PDGF-BB 通过 VEGF-Notch 信号通路和 PI3K-Akt 信号，促进创面愈合，并可以从分子层面促进糖尿病创面中的成血管作用，为糖尿病创面的临床治疗开辟新的途径。