靜息態(tài)或M2表型的小膠質(zhì)細(xì)胞主要由葡萄糖通過(guò)氧化磷酸化為細(xì)胞提供能量，病理?xiàng)l件下的M1促炎型小膠質(zhì)細(xì)胞即使在氧氣充足條件下，葡萄糖也會(huì)被優(yōu)先用于糖酵解生成大量乳酸，三羧酸循環(huán)受到抑制。蛋白激酶 B（Akt）及AMP依賴的蛋白激酶（AMPK）/哺乳動(dòng)物雷帕霉素靶蛋白（mTOR）/缺氧誘導(dǎo)因子-1α（HIF-1α）信號(hào)通路在調(diào)節(jié)糖酵解與炎癥反應(yīng)過(guò)程中發(fā)揮重要作用。小膠質(zhì)細(xì)胞中糖酵解與炎癥存在制約關(guān)系，抑制糖代謝重編程能夠干預(yù)小膠質(zhì)細(xì)胞 M1炎癥表型極化狀態(tài)，可以作為抑制神經(jīng)炎癥的藥物作用靶點(diǎn)，為退行性疾病、腦血管疾病等相關(guān)藥物的研發(fā)提供新思路。

Resting-state or M2 phenotype microglia are mainly energized by oxidative phosphorylation of glucose, and M1 proinflammatory microglia under pathological conditions are preferentially used for glycolysis to generate large amounts of lactate even under oxygen-sufficient conditions, and the tricarboxylic acid cycle is inhibited. The serine/threonine kinase (Akt) and AMPdependent protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway plays an important role in regulating glycolysis and inflammatory responses. Glycolysis in microglia is restricted to inflammation. Inhibition of glucose metabolism reprogramming can intervene the polarization state of M1 inflammatory phenotype in microglia, which can be used as a drug target to inhibit neuroinflammation and provide new ideas for the research and development of degenerative diseases, cerebral ischemia and other related drugs.

“十三五”期間天津市高等學(xué)校創(chuàng)新團(tuán)隊(duì)培養(yǎng)計(jì)劃（TD13-5050）