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

发布时间：2019-05-11 14:35

【摘要】：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90 s),每天持续8 h。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 protein78,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P0.01);而在IH+TUDCA组中,TUDCA能够显著地减少上述蛋白的表达(均P0.05)。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。
[Abstract]:Aim: to investigate the mechanism of inhibitory effect of sodium taurocholate (tauroursodeoxycholic acid sodium,TUDCA) on apoptosis in lung tissue of intermittent hypoxia (intermittent hypoxia,IH) model mice. Methods: thirty-two C57 mice were randomly divided into control group, TUDCA group, IH group and IH TUDCA group with 8 mice in each group. C57 mice were treated with IH in hypoxia chamber for 4 weeks (oxygen concentration decreased from 21% to 10%, and then recovered from 10% to 21% as a cycle, each cycle lasted for 90 s), for 8 h. 4 weeks after IH treatment. The expression of caspase-12 and cleaved caspase-3 in lung tissue was detected by Western. At the same time, the expression of glucose regulated protein 78 (glucose regulated protein78,GRP78 and CCAAT/ enhanced binding protein homologous protein (CCAAT/enhancer-binding protein homologous protein,CHOP) was detected by Western imprinting, immunohistochemistry and real-time quantitative PCR. Results: compared with the control group and TUDCA group, the expression of caspase-12,cleaved caspase-3,GRP78 and CHOP in lung tissue of IH group was significantly higher than that of control group and CHOP group (both P 0.01), while in IH TUDCA group, TUDCA could significantly decrease the expression of the above proteins (all P 0.05). Conclusion: chronic IH can induce endoplasmic reticulum stress-mediated apoptosis in lung tissue, while TUDCA can reduce the apoptosis level by inhibiting the activation of endoplasmic reticulum stress.
【作者单位】：中南大学湘雅二医院呼吸内科;
【基金】：国家重点临床专科建设项目(2012 650)~~
【分类号】：R285.5;R-332

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