OBJECTIVES: To investigate the role of lactate in myocardial ischemia-reperfusion (MIR)-induced gastric mucosal injury. METHODS: Thirty C57BL/6J mice were randomized into sham-operated group, MIR (45 min ischemia and 2 h reperfusion) group, and MIR+LDHAI group, and gastric mucosal injury was assessed using macroscopic scoring and HE staining; serum lactate and cTnT levels were measured using ELISA. Metabolomics analysis was conducted to identify the differential serum metabolites between the sham-operated and MIR mice. In the cell experiment, human gastric mucosal cells (GES-1) were indirectly co-cultured with THP-1 cell-derived macrophages polarized to the M1 phenotype by lactate and/or lipopolysaccharide (LPS) stimulation. In both the gastric mucosa tissues of the mice and the co-cultured GES-1 cells, the protein expression levels of CD68, iNOS, Arg-1, COX-1, and COX-2 were detected using Western blotting and immunofluo-rescence staining. RESULTS: Compared to sham operation, MIR induced concurrent injury in both the heart and stomach of the mice and caused elevation of iNOS protein levels and reduction of Arg-1 protein expression in the gastric mucosa, where increased overlapping fluorescent areas were detected after MIR using fluorescent double-labeling for CD68 and iNOS. Serum metabolomics analysis revealed a significant increase in circulating lactate levels after MIR. In GES-1 cells, indirect co-culture with M1 macrophages induced obvious cell injury, decreased COX-1 expression, and increased cellular COX-2 protein expression. Western blotting and immunofluorescence staining confirmed that 15 mmol/L lactate significantly increased iNOS and decreased Arg-1 expression in THP-1-derived macrophages. Indirect co-culture of GES-1 cells with M1 macrophages induced by lactate or LPS resulted in obvious GES-1 cell injury. In the mouse models of MIR, inhibition of lactic acid production effectively alleviated MIR-induced gastric mucosal injury. CONCLUSIONS: Lactate-induced M1 macrophage polarization mediates MIR-related gastric mucosal injury in mice via the heart-gastric axis, an effect reversible by LDHA inhibition. 目的: 探讨乳酸介导心肌缺血再灌注（MIR）诱导胃黏膜损伤的现象及机制。方法: 动物实验:30只C57BL/6J小鼠随机分为Sham组、MIR组（心肌缺血45 min，再灌注2 h）以及MIR+乳酸脱氢酶A抑制组（MIR+LDHAI组），每组10只。细胞实验:采用浓度梯度乳酸（0、5、15、30 mmol/L）刺激人单核细胞THP-1来源巨噬细胞极化;将人胃黏膜细胞 GES-1与乳酸或脂多糖（LPS）诱导的 M1型极化巨噬细胞间接共培养，并设置Control组（M0细胞上清）、LPS-M1组（含100 ng/mL LPS的M1细胞上清）以及Lactate-M1 组（含15 mmol/L乳酸的M1细胞上清）。采用胃黏膜损伤评定量化表进行胃黏膜大体观损伤量化评分;采用 HE染色观察心肌组织和胃黏膜组织病理改变;采用ELISA检测血清乳酸和cTnT水平;采用Western blotting和（或）免疫荧光法检测组织和（或）细胞中CD68、iNOS、Arg-1、COX-1和COX-2表达;采用代谢组学方法分析Sham和MIR两组血清代谢产物的差异。结果: MIR同时造成心脏和胃的损伤，表现为心肌组织水肿以及心肌细胞坏死，胃黏膜组织结构紊乱伴随免疫细胞浸润;Western blotting和免疫荧光染色显示MIR后胃黏膜组织iNOS蛋白水平增加，Arg-1蛋白表达降低，进一步采用荧光双重标记 CD68和iNOS，发现MIR后重叠的荧光区域增加，提示发生巨噬细胞M1型极化（P<0.05）。光镜下发现与M1型巨噬细胞间接共培养可诱导GES-1细胞损伤;Western blotting和免疫荧光染色提示M1细胞间接共培养诱导GES-1细胞COX-1蛋白表达减少，COX-2蛋白表达增加（P<0.05）。检测小鼠血清代谢组学提示MIR后循环乳酸的水平增加（P<0.05）。Western blotting和免疫荧光染色显示15 mmol/L乳酸诱导THP-1来源巨噬细胞M1型极化，表现为iNOS表达增加，Arg-1表达减少（P<0.05）;与乳酸和（或）LPS诱导的M1型巨噬细胞间接共培养诱导GES-1细胞损伤;抑制乳酸生成减轻MIR诱导的胃黏膜损伤，表现为胃黏膜组织结构改善和免疫细胞浸润减少。结论: 乳酸诱导巨噬细胞M1型极化参与MIR诱导的胃黏膜损伤，抑制乳酸生成可缓解乳酸通过“心-胃轴”造成的胃黏膜损伤。.