乳酸对炎症的调节作用研究进展

Research Progress in Regulation of Inflammation by Lactic Acid

乳酸一直被认为是葡萄糖代谢的副产物,但自从发现乳酸作为信号分子在细胞内和细胞外具有信号转导功能,并在调节各种生理和病理过程中发挥重要作用以来,这种观点发生了变化。近年来国内外的研究积累了大量数据,证明乳酸对炎症过程具有调控作用,但目前是否可以将乳酸视为促炎介质或抗炎介质,尚无定论。在急性炎症性疾病中,乳酸主要通过激活G蛋白偶联受体81(GPR81)及单羧酸转运载体(MCT)、促进巨噬细胞极化、充当组蛋白去乙酰化酶(HDAC)抑制剂等发挥抗炎作用;在慢性炎症性疾病中,乳酸通过激活G蛋白偶联受体4(GPR4)、调节T细胞运动、诱导细胞外信号调节激酶(ERK)和蛋白激酶B(AKT)通路等发挥促炎作用。本文总结了乳酸在炎症过程中的多效性作用的最新研究进展和乳酸信号传导机制,以期为今后炎症调控的研究提供参考。

Lactic acid has long been considered a waste product of glucose metabolism,but this view has changed since the discovery that lactic acid acts as a signaling molecule with signal transduction functions both inside and outside the cell and plays an important role in regulating various biological and pathological proces⁃ses.In recent years,a large amount of evidence has been accumulated in vivo and in vitro to prove that lactic acid plays a regulatory role in the inflammatory process.However,whether lactic acid can be regarded as a pro⁃inflammatory or anti⁃inflammatory medium is still uncertain.In acute inflammatory diseases,lactic acid plays an anti⁃inflammatory role mainly through G protein⁃coupled receptors(GPR)81,monocarboxylic acid transporter(MCTs),promoting macrophage polarization and acting as an histone deacetylase inhibitor.Lactic acid plays a pro⁃inflammatory role in chronic inflammation through GPR4,regulation of T cell motility,and induction of extracellular regulated protein kinases 1/2(ERK1/2)and protein kinase B(AKT)pathways.In this paper,we summarized the recent progress of the polytope of lactic acid in the inflammatory process and the signal transduction mechanism of lactic acid,so as to provide reference for future research.