PKCβⅡ调控内皮细胞血管生成在急性波动性高血糖延迟伤口愈合中的作用及机制研究

There may be a dramatic blood glucose increase in the case of burns, acute trauma, critical infection, perioperative stress state. Even if treated with glucose-lowering treatment, the acute glucose fluctuation is avoidless under the strong stress situation. The Chronic hyperglycemia has been shown to delay the wound healing, is it the same for acute glucose fluctuation? In our previous researches and preliminary experiment, acute glucose fluctuation contributed to delay the wound healing and cause endothelial apoptosis which can be attenuated by PKCβ inhibitor, so we conclude that PKCβⅡ plays a critical role in the delay of wound healing. In the study, in vitro and in vivo researches will be performed to validate how acute glucose fluctuation affect angiogenic function of endothelial cells and endothelial progenitor cells, to confirm whether PKCβⅡ signaling pathway contribute to angiogenesis and cell apoptosis; whether acute glucose fluctuation delay the wound healing by affecting endothelial survival and angiogenesis and whether PKCβⅡ inhibitor intervention can accelerate wound healing will be elucidated by constructing wound healing rats model. This research will study the mechanism how acute glucose fluctuation affects wound healing and the regulation of PKCβⅡ from organ, cell and molecular viewpoint. The mechanism and therapeutic target could be provided for wound healing delay under acute glucose fluctuation condition.

机体在烧伤、急性创伤、重症感染、围手术期等应激状态下可能会出现血糖急剧升高。此时给予降糖治疗，虽可降低血糖，但因机体处于强烈应激状态而常常无法有效的避免急性血糖波动。研究显示慢性高血糖会延迟伤口愈合, 那么急性波动性高血糖是否会延迟伤口愈合？申请人的前期研究及预实验发现，急性血糖波动能引起内皮细胞凋亡及伤口愈合延迟，PKCβ抑制剂可延缓这一进程。因此我们推测PKCβⅡ在急性血糖波动延迟伤口愈合中起重要作用。本课题将通过体内和体外实验研究急性血糖波动对内皮细胞血管生成的影响，及PKCβⅡ是否参与调控血管生成及细胞凋亡；建立伤口愈合大鼠模型，研究急性血糖波动是否影响内皮细胞存活和血管生成，造成伤口延迟愈合，以及PKCβⅡ在其中的作用及其机制。本课题拟在器官、细胞及分子水平上探讨急性血糖波动对伤口愈合的影响，及PKCβⅡ的调控作用。为探讨急性波动性高血糖延迟伤口愈合的机制及治疗靶点提供新思路。

剧烈的急性血糖波动会引起内皮细胞凋亡及伤口愈合延迟，本课题通过建立急性血糖波动模型，探讨PKCβ在急性血糖波动延迟伤口愈合中起重要作用。通过体内和体外实验研究急性血糖波动对内皮细胞血管生成的影响，PKCβ参与调控血管生成及细胞凋亡的机制；建立伤口愈合大鼠模型，研究急性血糖波动是否影响内皮细胞存活和血管生成，造成伤口延迟愈合，以及PKCβ在其中的作用及其机制。本课题在器官、细胞及分子水平上探讨急性血糖波动对伤口愈合的影响，及PKCβ的调控作用。综合上述结果，本研究为探讨急性波动性高血糖延迟伤口愈合的机制及治疗靶点提供了坚实的工作基础及思路。项目资助发表SCI论文6篇（主持人为通讯作者），协助培养硕士生3名。项目投入经费20万元，支出17.8069万元，各项支出基本与预算相符。剩余经费2.1913万元，剩余经费计划用于本项目研究后续支出。