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摘要: 探讨了蛋白质乳酸化修饰（protein lactylation modification，Kla）在脓毒症及多器官功能障碍（multiple organ dysfunction syndrome，MODS）中的作用机制。Kla通过调控基因转录与炎症因子表达，参与脓毒症器官功能损伤，还可破坏细胞结构与代谢稳态，加重脓毒症引发的肺、肾、心、脑、肝器官损伤。因此，深入研究其机制，有助于挖掘新治疗靶点，为脓毒症临床治疗提供创新思路。Abstract: This article aims to explore the mechanism of protein lactate modification （Kla） in sepsis and multiple organ dysfunction syndrome （MODS）. By regulating gene transcription and inflammatory factor expression, Kla participates in sepsis organ function damage, and can also destroy the cell structure and metabolic homeostasis, aggravating sepsis induced lung, kidney, heart, brain, liver organ damage. By conducting in-depth study on its mechanism, it will help to explore new therapeutic targets and provide innovative ideas for clinical treatment of sepsis.
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Key words:
- Protein lactylation modification /
- Sepsis /
- Multiple organ dysfunction
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图 1 Kla修饰的全局调控网络图
LDHA：乳酸脱氢酶A；HDACs：组蛋白去乙酰化酶；P300：E1A结合蛋白p300；MCT4：单羧酸转运蛋白4；MCT1：单羧酸转运蛋白1；PDHA1：丙酮酸脱氢酶E1亚基α；HMGB1：高迁移率族蛋白B1；NF-κB：核因子κB；H3K4：组蛋白H3第4位赖氨酸；H3K18：组蛋白H3第18位赖氨酸；H3K27：组蛋白H3第27位赖氨酸；H4K12：组蛋白H4第12位赖氨酸；la：乳酸化修饰。
Figure 1. Global regulatory network diagram modified with Kla
图 2 Kla在脓毒症肺损伤的作用机制
EGR1：早期生长反应因子1；HPSE：肝素酶；H3K18：组蛋白H3第18位赖氨酸；la：乳酸化修饰。
Figure 2. The mechanism of action of Kla in sepsis induced lung injury
图 3 Kla在脓毒症肾损伤的作用机制
H4K12：组蛋白H4第12位赖氨酸；H3K18：组蛋白H3第18位赖氨酸；Bay11-7082：NF-κB通路抑制剂；Y-27632：ROCK激酶抑制剂；RhoA/ROCK/Ezrin通路：RhoA-ROCK-Ezrin通路；NF-κB通路：核因子κB通路；TNF-α：肿瘤坏死因子-α；IL-6：白细胞介素-6；la：乳酸化修饰。
Figure 3. The mechanism of action of Kla in sepsis induced kidney injury
图 4 Kla在脓毒症心脏损伤的作用机制
KAT2A：赖氨酸乙酰转移酶2A；HADHA k166/k728：脂肪酸氧化关键酶 第166位赖氨酸/第728位赖氨酸；IL6：白细胞介素-6；BAX：促凋亡蛋白；la：乳酸化修饰。
Figure 4. The mechanism of action of Kla in sepsis induced cardiac injury
图 5 Kla在脓毒症脑损伤的作用机制
NuRD复合体：核小体重塑与去乙酰化复合体；HDAC1：组蛋白去乙酰化酶1；H1：组蛋白H1；IL-1β：白细胞介素-1β；TNF-α：肿瘤坏死因子-α；la：乳酸化修饰。
Figure 5. The mechanism of action of Kla in sepsis induced brain injury
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