Glycolysis Inhibition Alleviates Cardiac Fibrosis After Myocardial Infarction by Suppressing Cardiac Fibroblast Activation.
Glycolysis Inhibition Alleviates Cardiac Fibrosis After Myocardial Infarction by Suppressing Cardiac Fibroblast Activation.
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糖酵解抑制通过抑制心脏成纤维细胞活化减轻心肌梗塞后的心脏纤维化
DOI：
10.3389/fcvm.2021.701745
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发表时间：
2021
影响因子：
3.6
通讯作者：
Chen YX
中科院分区：
文献类型：
--
作者：
Chen ZT;Gao QY;Wu MX;Wang M;Sun RL;Jiang Y;Guo Q;Guo DC;Liu CY;Chen SX;Liu X;Wang JF;Zhang HF;Chen YX
目的：探讨糖酵解在心肌梗死（MI）后心肌成纤维细胞（CF）活化及心肌纤维化中的作用。方法：体内实验：每天向MI或假手术小鼠腹腔注射糖酵解抑制剂2-脱氧-D-葡萄糖（2-DG）。第28天，超声心动图测定心功能，并切取心脏。Masson染色和免疫荧光法（IF）检测纤维化面积，Western blot检测糖酵解水平。在体外，我们分离了假手术组、心肌梗死组和2-DG治疗组小鼠的CF，并用转化生长因子-β1（transforming growth factor-β1，TGF-β1）激活正常CF，并用2-DG阻断糖酵解。然后检测糖酵解蛋白、纤维化蛋白以及培养基中乳酸和葡萄糖的浓度。最后，我们进一步用Masson染色、IF和western blot检测了人纤维化和非纤维化心脏组织中的纤维化和糖酵解标志物。结果：MI小鼠心肌胶原和糖酵解蛋白表达增加。2-DG（100 mg/kg/d）组小鼠心肌梗死术后死亡率明显高于对照组（Log-rank检验，P < 0.05）。当2-DG剂量降至50 mg/kg/d，并在MI后第4天开始给药时，两组动物的死亡率无统计学差异（Log-rank检验，P = 0.98）。2-DG组胶原体积分数较PBS组小，α-平滑肌肌动蛋白（α-SMA）荧光信号较PBS组弱。在体外，2-DG可显著抑制激活CF中糖酵解和纤维化蛋白的表达增加。结论：心肌纤维化沿着CF活化和糖酵解的增强。糖酵解抑制剂可减轻心肌梗死后心肌成纤维细胞活化和心肌纤维化。
Objective: To explore the role of glycolysis in cardiac fibroblast (CF) activation and cardiac fibrosis after myocardial infarction (MI). Method: In vivo: 2-Deoxy-D-glucose (2-DG), a glycolysis inhibitor, was injected into the abdominal cavity of the MI or sham mice every day. On the 28th day, cardiac function was measured by ultrasonic cardiography, and the hearts were harvested. Masson staining and immunofluorescence (IF) were used to evaluate the fibrosis area, and western blot was used to identify the glycolytic level. In vitro, we isolated the CF from the sham, MI and MI with 2-DG treatment mice, and we also activated normal CF with transforming growth factor-β1 (TGF-β1) and block glycolysis with 2-DG. We then detected the glycolytic proteins, fibrotic proteins, and the concentrations of lactate and glucose in the culture medium. At last, we further detected the fibrotic and glycolytic markers in human fibrotic and non-fibrotic heart tissues with masson staining, IF and western blot. Result: More collagen and glycolytic protein expressions were observed in the MI mice hearts. The mortality increased when mice were treated with 2-DG (100 mg/kg/d) after the MI surgery (Log-rank test, P < 0.05). When the dosage of 2-DG declined to 50 mg/kg/d, and the treatment was started on the 4th day after MI, no statistical difference of mortality between the two groups was observed (Log-rank test, P = 0.98). The collagen volume fraction was smaller and the fluorescence signal of α-smooth muscle actin (α-SMA) was weaker in mice treated with 2-DG than PBS. In vitro, 2-DG could significantly inhibit the increased expression of both the glycolytic and fibrotic proteins in the activated CF. Conclusion: Cardiac fibrosis is along with the enhancement of CF activation and glycolysis. Glycolysis inhibition can alleviate cardiac fibroblast activation and cardiac fibrosis after myocardial infarction.
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影响因子：
6.1
作者：
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通讯作者：
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影响因子：
10
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DOI：
10.1016/j.bbrc.2019.06.055
发表时间：
2019-08-27
影响因子：
3.1
作者：
Hu, Heng-Jing;Zhang, Chi;Jiang, Zhi-Sheng
通讯作者：
Jiang, Zhi-Sheng
DOI：
10.1152/ajprenal.00422.2018
发表时间：
2019-06-01
影响因子：
4.2
作者：
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通讯作者：
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影响因子：
9
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