基于“虚气留滞”理论探讨血管内皮细胞自噬对糖尿病大血管病变的影响

Autophagy of Vascular Endothelial Cells Influences Diabetic Macroangiopathy:Based on Theory of Qi Deficiency and Stagnation

糖尿病大血管病变的基本病理改变是动脉粥样硬化(AS),其发生主要与血管内皮细胞(VECs)损伤、氧化应激、糖脂代谢紊乱、血液流变学异常、内质网应激等机制相关。VECs损伤和功能障碍是糖尿病大血管病变的始动因素。自噬是亚细胞水平的自我保护机制,通过溶酶体介导蛋白质和受损细胞器的降解调控细胞内基本代谢,维持机体内稳态。VECs自噬不足可致VECs的炎症、凋亡、氧化应激增强,从而促进AS。中医认为糖尿病大血管病变乃本虚标实之证,“虚气留滞”是关键病机。虚气不荣,以虚为本;留滞难通,以滞为标。营卫不和、脉道失稳为病之先因,肾气不足、化充乏源为病之主因,脏腑气血相失、气血津液停滞积为病之内因,病理产物滞留血脉、损伤脉管为病之表因。自噬乃气之微观表现,同具有祛病邪、维稳态之功。VECs自噬不足致虚气留滞,气虚渐、滞留重,亦致自噬之效不及,形成恶性循环。现代研究表明,调控VECs自噬是防治AS的主要途径,而中医药具有多靶点、多途径整合调控之优势。故基于“虚气留滞”理论,以“荣体之虚,通脉之滞”为法,选方遣药调控VECs自噬、对抗AS,对延缓糖尿病大血管病变进程具有重要意义。

The basic pathological change of diabetic macroangiopathy is atherosclerosis(AS),which is mainly associated with vascular endothelial cells(VECs)injury,oxidative stress,glucose and lipid metabolism disorders,hemorheological abnormalities,and endoplasmic reticulum stress.The injury and dysfunction of VECs are the initiating factors of diabetic macroangiopathy.Autophagy is a subcellular self-protection mechanism that regulates basic intracellular metabolism through lysosome-mediated degradation of proteins and damaged organelles to maintain homeostasis.Insufficient autophagy of VECs leads to enhanced inflammation,apoptosis,and oxidative stress of VECs,which promotes AS.According to the theory of traditional Chinese medicine(TCM),diabetic macroangiopathy corresponds to the syndrome of internal deficiency and pathogen invasion,with Qi deficiency and stagnation as the key pathogenesis.Qi deficiency is the root cause,and Qi stagnation is the manifestation.The disease occurs with the initial cause of nutrient-defense disharmony and instability of vessels,the main cause of the deficiency of kidney Qi and the lack of source for generation and transformation,the internal cause of Qi and blood loss in the viscera and the stagnation of Qi,blood,and fluid,and the superficial cause of the stagnation of pathological products and the damage of vessels.Autophagy is a microscopic manifestation of Qi,which has the function of dispelling pathogens and maintaining homeostasis.Insufficient autophagy of VECs leads to Qi deficiency and stagnation,and the gradual deficiency and heavy stagnation of Qi lead to insufficient autophagy,which form a vicious cycle.Modern research has demonstrated that regulating the autophagy of VECs is the main way to prevent and treat AS,and TCM can exert the therapeutic effect in a multi-target and multi-pathway manner.Therefore,based on the theory of Qi deficiency and stagnation,the method of tonifying deficiency of and removing stagnation can be adopted to select prescriptions for regulating the autophagy of VECs and treating AS,which can slow down the procession of diabetic macroangiopathy.