糖尿病周围神经病变中磷酸磷脂酶Lipin1对线粒体质量控制调控作用研究

Diabetic Peripheral Neuropathy (DPN) is one of the most common chronic complications of diabetes. It seriously affects the patient life expectancy and quality of life; however, the exact mechanism is still unclear. Our previous study has shown that the expression of phosphatidic acid phosphohydrolase Lipin1 in peripheral sciatic nerve and Schwann cell decreased in high glucose environment. It is known that Lipin1 is the key enzyme that regulates phospholipid metabolism. Knockdown Lipin1 in Hela and NIH3T3 cells can cause disorganization of the mitochondrial mass control (MQC). Our further study found that there are also mitochondrial quality control disorders in DPN. Therefore, our proposal intends to use diabetic and Lipin1-/- knockout animal models and mainly focus on the followings: (1) The regulation of Lipin1 on the mitochondrial quality control of peripheral nerve mitochondria fusion, fission and mitophagy; (2) To explore the key role and mechanism of Lipin1 in regulating MQC disorder in DPN at in vivo level, so as to provide new ideas and theoretical basis for the prevention and treatment of DPN.

糖尿病周围神经病变（DPN）是糖尿病最常见的慢性并发症之一，严重影响患者寿命和生活质量，但具体机制不明。我们前期研究发现：高糖环境下外周坐骨神经和雪旺细胞磷脂酸磷酸酶Lipin1表达下降。已知Lipin1是调控磷脂代谢的关键酶，在Hela和NIH3T3细胞中Lipin1缺失可导致线粒体质量控制（MQC）紊乱。我们进一步研究发现DPN中亦存在线粒体质量控制紊乱。据此，本项目拟以糖尿病动物模型和Lipin1-/-基因敲除动物为对象，重点研究：（1）Lipin1对外周神经线粒体分裂/融合、自噬等线粒体质量控制环节的调控作用；（2）在整体水平探讨Lipin1调控MQC紊乱在DPN发病中的关键作用及机理，从而为DPN的预防和治疗提供新的思路和理论依据。

糖尿病周围神经病变（DPN）是糖尿病最常见的慢性并发症之一，严重影响患者寿命和生活质量，但具体机制不明。我们前期研究发现：高糖环境下外周坐骨神经和雪旺细胞磷脂酸磷酸酶Lipin1表达下降。已知Lipin1是调控磷脂代谢的关键酶，在Hela和NIH3T3细胞中Lipin1缺失可导致线粒体质量控制（MQC）紊乱。我们进一步研究发现DPN中亦存在线粒体质量控制紊乱。据此，本项目拟以糖尿病动物模型和Lipin1-/-基因敲除动物为对象，重点研究：（1）Lipin1对外周神经线粒体分裂/融合、自噬等线粒体质量控制环节的调控作用；（2）在整体水平探讨Lipin1调控MQC紊乱在DPN发病中的关键作用及机理，从而为DPN的预防和治疗提供新的思路和理论依据。