Enhancement of morphine analgesia and prevention of morphine tolerance by downregulation of β-arrestin 2 with antigene RNAs in mice
Enhancement of morphine analgesia and prevention of morphine tolerance by downregulation of β-arrestin 2 with antigene RNAs in mice
复制标题
通过反基因 RNA 下调 β-arrestin 2 增强吗啡镇痛并预防吗啡耐受
DOI：
10.3109/00207454.2014.896913
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发表时间：
2015-01-01
影响因子：
2.2
通讯作者：
Gao, Feng
中科院分区：
文献类型：
--
作者：
Bu, Huilian;Liu, Xijiang;Gao, Feng
β-arrestin 2是G蛋白偶联受体的调节分子，在μ阿片受体功能调节中起重要作用。β-arrestin 2表达的改变可能影响μ阿片受体的功能及其激动剂的作用。本研究利用能选择性靶向基因转录起始位点并有效抑制基因表达的反义RNA（antigene RNA，agRNA）下调β-arrestin 2的表达，探讨其对小鼠吗啡镇痛和耐受的影响。在向小鼠脑室内施用编码β-arrestin 2 agRNA的重组慢病毒后，β-arrestin 2表达显著降低超过3周。用β-arrestin 2 agRNA处理的小鼠显示出对吗啡的响应增强的镇痛作用，并且未能产生抗伤害性耐受。这些结果表明，在大脑中抑制β-arrestin 2与特定的agRNA可以提高吗啡的疗效，从而为我们提供了一个有用的策略，在体内治疗慢性顽固性疼痛和吗啡耐受。
beta-arrestin 2, a regulatory molecule of G protein-coupled receptor, has been proved to play an important role in regulating functions of mu opioid receptor. Changes of beta-arrestin 2 expression might affect the function of mu opioid receptors and the effect of its agonists. In this study, antigene RNAs (agRNAs), which could selectively target gene transcription start sites and potently inhibit gene expression, were used to downregulate the expression of beta-arrestin 2 to investigate its effects on morphine analgesia and tolerance in mice. After intracerebroventricular administration of recombinant lentivirus encoding beta-arrestin 2 agRNAs to the mice, beta-arrestin 2 expression was significantly decreased for more than 3 weeks. Mice treated with beta-arrestin 2 agRNAs showed enhanced analgesic effects in response to morphine and failed to develop antinociceptive tolerance. These results suggest that inhibition of beta-arrestin 2 in the brain with specific agRNAs can improve morphine efficacy, and consequently provide us a useful strategy for treatment of chronic intractable pain and morphine tolerance in vivo.