牛磺熊去氧胆酸钠抑制小鼠间歇性低氧模型肺组织中内质网应激的激活

目的：探究牛磺熊去氧胆酸钠(tauroursodeoxycholic acid sodium，TUDCA)在间歇性低氧(intermittent hypoxia，IH)模型小鼠肺组织中抑制细胞凋亡的机制。方法：32只C57小鼠随机分为对照组、TUDCA组、IH组和IH+TUDCA组，每组8只。将C57小鼠放入低氧舱中进行IH处理4周 (氧气浓度从21%下降到10%，再从10%恢复到21%为一个循环，每个循环的时间为90s)，每天持续8h。4周IH处理后，Western印迹检测caspase-12和cleaved caspase-3在肺组织中的表达。同时，Western印迹、免疫组织化学和实时定量PCR检测葡萄糖调节蛋白78(glucose regulated protein 78，GRP78) 和CCAAT/增强结合蛋白同源蛋白(CCAAT/enhancer-binding protein homologous protein，CHOP)的表达。结果：与对照组和TUDCA组相比，IH组小鼠肺组织中caspase-12，cleaved caspase-3，GRP78和CHOP表达明显升高(均P<0.01)；而在IH+TUDCA组中，TUDCA能够显著地减少上述蛋白的表达(均P<0.05)。结论：慢性的IH能够导致肺组织中内质网应激介导的细胞凋亡，而TUDCA可以通过抑制内质网应激的激活来降低细胞的凋亡水平。

Tauroursodeoxycholic acid suppresses endoplasmic reticulum stress in pulmonary tissues of intermittent hypoxia mice

Objective: To explore the mechanism of tauroursodeoxycholic acid (TUDCA) in suppressing apoptosis in pulmonary tissues of intermittent hypoxia (IH) mice model. Methods: A total of 32 C57 mice were randomly divided into a control group, a TUDCA group, an IH group and an IH+TUDCA group (8 mice per group). The mice were put in specially designed chambers and exposed to IH treatment for 4 weeks. In the chambers, oxygen levels repeatedly decreased from 21% to 10% and recovered from 10% to 21%, lasting for 8 hours in every day. After 4 weeks of IH exposure, the expression levels of caspase-12 and cleaved caspase-3 in pulmonary tissues were detected by Western blot. Meanwhile, the expression levels of glucose regulated protein-78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) were quantified by Western blot, immunochemistry and real-time PCR. Results: Compared with the control group, the expression levels of caspase-12, cleaved caspase-3, GRP78 and CHOP were increased in the IH group (all P<0.01). TUDCA treatment could reduce these proteins expression (all P<0.05). Conclusion: Endoplasmic reticulum stress-mediated apoptosis can be activated in pulmonary tissues after chronic IH exposure, and TUDCA can reduce the cellular apoptosis via suppressing endoplasmic reticulum stress.