中文摘要
逐年增多的涉毒案件已对整个社会的和谐、稳定产生了极大的危害,阐明毒品成瘾的形成机制是法医学者所面临的重要课题。毒品成瘾与其他慢性神经系统疾病(如:抑郁症、阿尔兹海默症及帕金森症)以及非神经系统的慢性代谢病(如:2型糖尿病、高血压及动脉粥样硬化)存有共同的发病基础,即低度炎症,又被称为“para-inflammation”。过氧化物酶体增殖激活物受体(PPARs)是一类核受体,其相关配体作为传统治疗2型糖尿病和高血脂的药物(如:皮格列酮、吉非贝齐),能明显缓解这些疾病所累及器官的炎症反应,亦可显著改善阿尔兹海默症、帕金森症患者相关脑区的炎症反应,我们的预实验结果也显示PPARs相关配体能明显减低成瘾动物伏隔核脑区的炎症反应并阻滞其成瘾行为形成。基于此,本项目拟以PPARs介导的抗炎作用为切入点,深入探讨该机制在毒品成瘾中的作用,以期为毒品成瘾机制的阐明及治疗提供新的角度和方法。
英文摘要
As a member of forensic scientists, it is our challenge to illustrate the mechanism of drug addiction, due to the increasing trend of drug-related cases in our country which has jeopardized social harmony and stability. Low-level inflammation, called as "para-inflammation", plays as a important role in drug addiction, which also persists in some other chronic neurological diseases (e.g., Depression, Alzheimer's Disease (AD) and Parkinson's Disease (PD)) and chronic metabolic diseases (e.g., Type-2 Diabetes (T2D), Hypertension and Atherosclerosis). Peroxisome Proliferator-Activated Receptors (PPARs) is a class of nuclear receptors. Their related ligands (e.g., Pioglitazone, Gemfibrozil) which are traditionally used to treat T2D and high cholesterol, can significantly reduce the inflammation in their related diseased organs, also ameliorate the inflammation in related brain area of AD and PD patients. And, the results in our preliminary experiments show a similar effect. That is, the related ligands of PPARs could lower the inflammation in nucleus accumbens in addictive animals; meanwhile, another group blocked the formation of addictive behavior. Based on the above findings, our project try to reveal the mechanism of drug addiction from perspective of the anti-inflammation of PPARs, which most likely provide a new interpretation for drug addiction and potentially contribute a new method for therapy.
