目的 探讨孕酮对皮质酮诱导的PC12抑郁症细胞模型的保护作用及其潜在机制。方法 CCK-8法检测细胞存活率筛选皮质酮(100、200、300、400、500、600μmol·L^-1)作用于PC12细胞构建抑郁症细胞模型；造模后，CCK-8法筛选孕酮(1、5、10、20、40、60、80μmol·L^-1)的治疗浓度；同时设定孕酮核受体（n PR）特异性抑制剂RU486和孕酮受体膜组分1（PGRMC1）特异性抑制剂AG205联合孕酮(10μmol·L^-1)处理组，加药后孵育36 h。流式细胞术检测凋亡情况；DCFHDA探针法测定细胞内活性氧（ROS）水平；钙离子荧光探针Fluo-4 AM法测定钙离子浓度；试剂盒法检测乳酸脱氢酶（LDH）释放情况；JC-1探针法检测线粒体膜电位，并采用Western blotting法分析凋亡相关蛋白的表达。结果 PC12抑郁症细胞模型采用皮质酮300μmol·L^-1制备，孕酮10μmol·L^-1作用效果较好；与模型组相比，孕酮显著降低细胞内ROS水平和钙离子浓度（P<0.01），减少LDH释放以及稳定线粒体膜电位（P<0.01），提高Bcl-2蛋白的表达（P<0.01），降低Bax、Cyt C、Caspase-3蛋白的表达（P<0.05），从而减少细胞凋亡（P<0.01），提升细胞活力（P<0.01）；且RU486和AG205均能抑制孕酮对抑郁症细胞模型的保护作用（P<0.05、0.01）。结论 孕酮能通过n PR以及PGRMC1减轻皮质酮诱导的PC12抑郁症细胞模型氧化应激反应以及细胞内钙超载，进而发挥神经保护作用。

Objective To explore the protective effect of progesterone on the corticosterone-induced PC12 depression cell model and its potential mechanism. Methods The CCK8 method was used to detect cell viability to screen the concentration of corticosterone(100, 200, 300, 400, 500, 600 μmol·L^-1) for the construction of the depression cell model in PC12 cells; After modeling, the CCK8 method was used to screen the therapeutic concentration of progesterone(1, 5, 10, 20, 40, 60, 80 μmol·L^-1); At the same time, the progesterone nuclear receptor（nPR） specific inhibitor RU486 and the progesterone receptor membrane component 1（PGRMC1） specific inhibitor AG205 combined with progesterone(10 μmol·L^-1) treatment groups were set up, and the cells were incubated for 36 h after drug addition. Apoptosis was detected by flow cytometry; intracellular reactive oxygen species（ROS） levels were detected by the DCFH-DA probe method, intracellular calcium ion concentration was detected by the calcium ion fluorescent probe Fluo-4 AM method; lactate dehydrogenase（LDH） release was detected by the kit method, and mitochondrial membrane potential was detected by the JC-1 probe method, and the expression of apoptosis-related proteins was analyzed by Western blotting. Results The PC12 depression cell model was prepared with 300 μmol·L^-1 corticosterone, and 10 μmol·L^-1 progesterone had a better effect; Compared with the model group, progesterone significantly reduced intracellular ROS levels and calcium ion concentration（P＜0.01）, reduced LDH release and stabilized mitochondrial membrane potential（P＜0.01）, increased the expression of Bcl-2 protein（P＜0.01）, decreased the expression of Bax, Cyt C, and Caspase-3 proteins（P＜0.05）, thereby reducing cell apoptosis（P＜0.01） and enhancing cell viability（P＜0.01）; and both RU486 and AG205 could inhibit the protective effect of progesterone on the depression cell model（P＜0.05, 0.01）. Conclusion Progesterone exerts neuroprotective effects by alleviating CORT-induced oxidative stress and intracellular calcium overload in the PC12 depression cell model through nPR and PGRMC1 pathways.

R965

河北省省属高校基本科研业务费自然科学研究计划项目(JYT2021001); 河北省研究生创新资助项目(CXZZSS2024129); 河北北方学院校级科研项目(XJ2023034)