牛磺熊去氧胆酸通过调控TBC1D15改善线粒体自噬减轻氧糖剥夺心肌细胞损伤的机制

doi:10.3969/j.issn.1006-5725.2026.02.007

Abstract

Abstract:

Objective ? To elucidate the mechanism by which tauroursodeoxycholic acid （TUDCA） alleviates oxygen-glucose deprivation （OGD）-induced cardiomyocyte injury through specific regulation of TBC1D15 protein expression and subcellular localization to restore mitophagy function. Methods ? Primary cardiomyocytes were subjected to OGD and treated with TUDCA at low （20 μmol/L）， medium （40 μmol/L）， or high （80 μmol/L） doses. TBC1D15 subcellular localization and expression were assessed by immunofluorescence. Cell apoptosis/necrosis was evaluated using YO-PRO-1/PI double staining. Lysosome staining is used to detect lysosome function. Autophagy dual-labeling adenovirus HBAD-mcherry-EGFP-LC3 is used to detect the efficiency of autophagy flow.Western blot was performed to analyze autophagy-related proteins （Beclin-1， LC3-Ⅱ/Ⅰ， p62） and the anti-apoptotic protein Bcl-2. Results Compared with the normal control group， the model group showed a significant decrease in TBC1D15 expression and disordered distribution. After TUDCA intervention， the expression of TBC1D15 was restored in a dose-dependent manner. In the high-dose group， the fluorescence intensity was close to that of the normal control group， and the localization at the cell membrane was significantly enhanced. Regarding autophagy-related indicators， the medium- and high- dose TUDCA groups significantly promoted autophagy activation， which was manifested as an increase in the LC3-Ⅱ/Ⅰ ratio， accelerated degradation of p62， and increased expression of Beclin-1. The results of cell apoptosis/necrosis detection showed that cell apoptosis/necrosis was significantly increased in the model group， while it was significantly alleviated after TUDCA intervention. Meanwhile， the expression of the anti - apoptotic protein Bcl-2 was up-regulated， and this ameliorative effect was most significant in the high- dose group. Conclusion TUDCA restores TBC1D15 membrane localization in a dose-dependent manner， subsequently activating the mitophagy pathway， and ultimately synergistically inhibits apoptosis/necrosis.

Key words: tauroursodeoxycholic acid, mitochondrial autophagy, TBC1D15, oxygen?glucose deprivation, cardiomyocyte injury

CLC Number:

R541

Weiyan LIAO,Qian ZHAO,Zeyu CHEN,Yue XUAN,Shengtao XIONG,Donglin LI,Xiao WANG. Mechanism of tauroursodeoxycholic acid improving mitochondrial autophagy and alleviating oxygen-glucose deprivation myocardial cell injury by regulating TBC1D15[J]. The Journal of Practical Medicine, 2026, 42(2): 220-229.

Figures/Tables 8

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References 27

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组别	自噬溶酶体数量	自噬小体数量	合计数量
正常对照组	483	211	694
模型组	68	438	506
TUDCA 低剂量组（20 μmol/L）	166	447	613
TUDCA 中剂量组（40 μmol/L）	284	250	534
TUDCA 高剂量组（80 μmol/L）	379	114	493

Mechanism of tauroursodeoxycholic acid improving mitochondrial autophagy and alleviating oxygen-glucose deprivation myocardial cell injury by regulating TBC1D15

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