慢性心理應(yīng)激通過β-AR-PKA通路促進腦膠質(zhì)瘤增殖的機制
發(fā)布時間:2018-03-04 02:13
本文選題:膠質(zhì)瘤 切入點:慢性心理應(yīng)激 出處:《基因組學(xué)與應(yīng)用生物學(xué)》2017年09期 論文類型:期刊論文
【摘要】:本研究旨在探討慢性心理應(yīng)激是否可以通過β-AR-PKA(β-adrenergic receptor,β-AR)信號通路調(diào)節(jié)乳酸生成進而促進膠質(zhì)瘤的增殖。首先構(gòu)建人膠質(zhì)瘤荷瘤裸鼠模型,待成瘤后通過束縛方法給予應(yīng)激刺激4周,觀察裸鼠皮下腫瘤增殖情況;ELISA檢測血清中腎上腺素(epinephrine,EPI)、去甲腎上腺素(norepinephrine,NE)及瘤組織乳酸的含量;RT-PCR及Western-blotting法檢測瘤組織LDHA的表達(dá)情況;用NE處理膠質(zhì)瘤LN229細(xì)胞模擬應(yīng)激刺激,同時加入β-AR-PKA信號通路抑制劑Propranolol及H89,檢測細(xì)胞中乳酸含量、LDHA表達(dá)及細(xì)胞增殖的情況。結(jié)果顯示給予應(yīng)激刺激后,荷瘤應(yīng)激組裸鼠皮下腫瘤體積增長明顯快于單純荷瘤組;荷瘤應(yīng)激組裸鼠EPI、NE、乳酸及瘤體中LDHA的表達(dá)均高于荷瘤組;Propranolol及H89均能有效抑制NE誘導(dǎo)的LN229細(xì)胞增殖、LDHA的表達(dá)及乳酸生成。本研究提示慢性心理應(yīng)激可以通過β-AR-PKA信號通路調(diào)節(jié)LDHA的表達(dá),而高濃度的乳酸進一步促進了腫瘤的增殖。
[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.
【作者單位】: 濰坊醫(yī)學(xué)院;濰坊醫(yī)學(xué)院生物化學(xué)與分子生物學(xué)教研室;
【基金】:山東省自然科學(xué)基金(ZR2014JL050) 山東省中醫(yī)藥科技發(fā)展計劃項目(2015-236) 山東省醫(yī)藥衛(wèi)生科技發(fā)展計劃項目(2015WSB27014)共同資助
【分類號】:R739.41
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本文編號:1563688
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