中国病理生理杂志2025，Vol.41Issue(6)：1200-1206,7.DOI:10.3969/j.issn.1000-4718.2025.06.017
3-溴丙酮酸通过抑制糖酵解缓解大鼠低氧性肺动脉高压
3-Bromopyruvic acid alleviates hypoxic pulmonary hypertension in rats by inhibiting glycolysis
摘要
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.关键词
3-溴丙酮酸/肺动脉高压/糖酵解/低氧/炎症Key words
3-bromopyruvic acid/pulmonary hypertension/glycolysis/hypoxia/inflammation分类
医药卫生引用本文复制引用
曹文傑,王万铁,余彩茶,黄曼,程缘,田云娜,徐俊鹏,汤程远,尤利益,胡纯..3-溴丙酮酸通过抑制糖酵解缓解大鼠低氧性肺动脉高压[J].中国病理生理杂志,2025,41(6):1200-1206,7.基金项目
温州市基础性科研项目(No.2022Y0235) （No.2022Y0235）
