慢性心理应激通过β-AR-PKA通路促进脑胶质瘤增殖的机制  

The Mechanism of the Chronic Psychological Stress on Promoting Proliferation of Brain Glioma by β-AR-PKA Signaling Pathway

作　　者：吕坤鹏 许清銮 王平[2] 李桂芝[2] 刘长江[2] 董俊红[2] 

机构地区：[1]潍坊医学院,生物技术专业潍坊261042 [2]潍坊医学院生物化学与分子生物学教研室,潍坊261042

出　　处：《基因组学与应用生物学》2017年第9期3558-3563,共6页Genomics and Applied Biology

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

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。The aim of this study was to explore whether chronic psychological stress could regulate the production of lactic acid to promote the proliferation of glioma through β-AR-PKA（β-adrenergic receptor,β-AR） signaling pathway.Firstly,a nude mouse model with human glioma was established.After tumor formation,the model received stress stimulation for 4 weeks by binding,and the proliferation of subcutaneous tumor in the nude mouse was observed.The contents of epinephrine（EPI）,norepinephrine（NE） and lactic acid in serum were determined by ELISA.RT-PCR and Western-blotting were used to detect the expression of LDHA in tumor tissues.LN229 cells were treated with NE to simulate stress.At the same time,β-AR-PKA signal pathway inhibitors Propranolol and H89 were added.Then,the lactic acid content,LDHA expression and cell proliferation were measured.The results showed that after stimulated by stress,the growth of subcutaneous tumor volume of nude mice in tumor-bearing stress group was significantly faster than the tumor-bearing group.The expression of EPI,NE,lactic acid and LDHA in tumor of nude mice was higher than that in tumor-bearing group.Propranolol and H89 both could effectively inhibit the proliferation of LN229 cells induced by NE,the expression of LDHA and the production of lactic acid.The results of this study revealed that chronic psychological stress could regulate the expression of LDHA through β-AR-PKA signaling pathway,while the lactic acid with high concentration might further promote the proliferation of the tumor.

关 键 词：胶质瘤 慢性心理应激 乳酸脱氢酶A(LDHA) 乳酸 

分 类 号：R739.41[医药卫生—肿瘤]