3-Bromopyruvic acid alleviates hypoxic pulmonary hypertension in rats by inhibiting glycolysis
10.3969/j.issn.1000-4718.2025.06.017
- VernacularTitle:3-溴丙酮酸通过抑制糖酵解缓解大鼠低氧性肺动脉高压
- Author:
Wenjie CAO
1
;
Caicha YU
;
Man HUANG
;
Yuan CHENG
;
Yunna TIAN
;
Jun-peng XU
;
Chengyuan TANG
;
Liyi YOU
;
Chun HU
;
Wantie WANG
Author Information
1. 温州医科大学基础医学院病理学与病理生理学系,浙江 温州 325035
- Publication Type:Journal Article
- Keywords:
3-bromopyruvic acid;
pulmonary hypertension;
glycolysis;
hypoxia;
inflammation
- From:
Chinese Journal of Pathophysiology
2025;41(6):1200-1206
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study aimed to confirm the glycolytic inhibitory activity of 3-bromopyruvic acid(3BP)and to assess whether this inhibition could ameliorate hypoxia-induced pulmonary hypertension in rats.METHODS:PAH model rats were generated from normal SD rats via exposure to normal pressure and hypoxia.Intervention groups I and II(6 rats per group)were then intraperitoneally injected with 3BP(15 mg/kg),and the normal and hypoxia groups(6 rats per group)were given the same amount of normal saline for a total of 21 d.The average pulmonary artery pressure of the rats in each group was measured via right heart catheterisation,and hilar tissue measurements.The right ventricle(RV),left ventricle,and interventricular septum(LV+S)were weighed,and the ratio of RV/(LV+S)was calculated as an index of right ventricular hypertrophy.Right lower lung tissues were fixed in 4%paraformaldehyde-PBS buffer,sec-tioned in conventional paraffin(5 μm thick),stained with HE and Masson,photographed under a microscope.Then the thickness ratio of the tunica media and the area ratio of collagen fibres were calculated.The expression of pyruvate kinase isozyme type M2(PKM2),nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),and pyruvate de-hydrogenase(PDH)proteins in the hilar tissues of each group were detected by western blot,whereas interleukin-1β(IL-1β)and IL-18 contents were detected using ELISA,and lactic acid content was detected using a lactic acid kit.RE-SULTS:The results showed that 3-brpa effectively inhibited glycolysis and significantly improved hypoxia-induced pulmo-nary hypertension in rats.Compared with the hypoxia group,in intervention group II,PKM2 expression was decreased(P<0.05),PDH expression increased significantly(P<0.01),and NLRP3 expression was decreased(P<0.05).The IL-18 and IL-1β contents decreased(P<0.05 or P<0.01,respectively).Pulmonary hemodynamic indexes showed that the pro-portion of the right ventricle and the mean pressure of the pulmonary artery decreased(P<0.05 or P<0.01,respectively).The HE and Masson staining results showed that the thickness ratio of the tunica media and the area ratio of collagen fibres decreased significantly(P<0.01).Lactic acid content was significantly decreased(P<0.01).CONCLUSION:This study showed that 3BP can inhibit glycolysis and alleviate hypoxia-induced pulmonary hypertension in rats.
