慢性心理应激通过β-AR-PKA通路促进脑胶质瘤增殖的机制

发布时间：2018-03-04 02:13

  本文选题：胶质瘤　切入点：慢性心理应激　出处：《基因组学与应用生物学》2017年09期 　论文类型：期刊论文

【摘要】：本研究旨在探讨慢性心理应激是否可以通过β-AR-PKA(β-adrenergic receptor,β-AR)信号通路调节乳酸生成进而促进胶质瘤的增殖。首先构建人胶质瘤荷瘤裸鼠模型,待成瘤后通过束缚方法给予应激刺激4周,观察裸鼠皮下肿瘤增殖情况;ELISA检测血清中肾上腺素(epinephrine,EPI)、去甲肾上腺素(norepinephrine,NE)及瘤组织乳酸的含量;RT-PCR及Western-blotting法检测瘤组织LDHA的表达情况;用NE处理胶质瘤LN229细胞模拟应激刺激,同时加入β-AR-PKA信号通路抑制剂Propranolol及H89,检测细胞中乳酸含量、LDHA表达及细胞增殖的情况。结果显示给予应激刺激后,荷瘤应激组裸鼠皮下肿瘤体积增长明显快于单纯荷瘤组;荷瘤应激组裸鼠EPI、NE、乳酸及瘤体中LDHA的表达均高于荷瘤组;Propranolol及H89均能有效抑制NE诱导的LN229细胞增殖、LDHA的表达及乳酸生成。本研究提示慢性心理应激可以通过β-AR-PKA信号通路调节LDHA的表达,而高浓度的乳酸进一步促进了肿瘤的增殖。
[Abstract]:The purpose of this study was to investigate whether chronic psychological stress can regulate lactic acid production through 尾 -AR-PKA (尾 -ARR) signaling pathway and promote the proliferation of glioma. To observe the proliferation of subcutaneous tumor in nude mice and to detect the content of lactic acid in serum of epinephrine nei (NE) and norepinephrine (NE), the expression of LDHA in tumor tissue was detected by RT-PCR and Western-blotting, and the LN229 cells of glioma treated with NE were treated with NE to simulate stress stimulation. At the same time, 尾 -AR-PKA signal pathway inhibitor Propranolol and H89were added to detect the expression of lactic acid and the proliferation of the cells. The results showed that the tumor volume of nude mice in the tumor-bearing stress group increased more rapidly than that in the simple tumor bearing group after stress stimulation. The expression of EPIN, lactic acid and LDHA in tumor-bearing stress group was significantly higher than that in tumor bearing group Propranolol and H89. This study suggests that chronic psychological stress can be mediated by 尾 -AR-PKA signal. The pathway regulates the expression of LDHA, The high concentration of lactic acid further promoted the proliferation of tumor.
【作者单位】： 潍坊医学院;潍坊医学院生物化学与分子生物学教研室;
【基金】：山东省自然科学基金(ZR2014JL050) 山东省中医药科技发展计划项目(2015-236) 山东省医药卫生科技发展计划项目(2015WSB27014)共同资助
【分类号】：R739.41
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本文编号：1563688