目的 探讨牛磺熊去氧胆酸（TUDCA）通过特异性调控TBC1D15蛋白表达和定位，恢复线粒体自噬功能，从而减轻氧糖剥夺（OGD）诱导的心肌细胞损伤的作用机制。 方法 采用传代心肌细胞H9c2OGD模型，设置正常对照组、模型组及TUDCA低（20 μmol/L）、中（40 μmol/L）、高（80 μmol/L）剂量干预组。通过免疫荧光检测TBC1D15亚细胞定位与表达，YO-PRO-1/PI双染评估细胞凋亡/坏死，溶酶体染色检测溶酶体功能并使用HBAD-mcherry-EGFP-LC3检测细胞自噬活性，Western blot分析自噬相关蛋白Beclin-1、LC3-Ⅱ/Ⅰ、p62及凋亡蛋白Bcl-2的表达情况。 结果 与正常对照组相比，模型组TBC1D15表达显著降低且分布紊乱；经TUDCA干预后，TBC1D15 表达呈剂量依赖性恢复，高剂量组荧光强度接近正常对照组水平，且细胞膜定位明显增强。在自噬相关指标方面，TUDCA 中、高剂量组显著促进自噬活化，具体表现为LC3-Ⅱ/Ⅰ比值升高、p62 降解加速以及Beclin-1表达增加。细胞凋亡/坏死检测结果显示，模型组细胞凋亡/坏死显著增加，而 TUDCA 干预后，细胞凋亡/坏死情况明显改善，同时抗凋亡蛋白Bcl-2表达上调，且这种改善效果在高剂量组最为显著。 结论 TUDCA通过剂量依赖性方式恢复TBC1D15蛋白的膜定位，进而激活线粒体自噬通路，最终协同抑制细胞凋亡/坏死。

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.