N-花生四烯酰乙醇胺及其类似物的神经保护作用

Neuroprotective effects of anandamide and its analogs

N-花生四烯酰乙醇胺(anandamide,AEA)属于内源性大麻素类长链脂肪酸衍生物,可通过大麻素受体(CB1/CB2)和(或)非CB1/CB2受体途径发挥神经保护作用。AEA类似物包括脂氨基酸类、脂肪酰乙醇胺类和甲基氟膦酸酯类化合物等。AEA类似物在生物活性及化学结构上与AEA相似,但作用靶点及作用机制并不完全相同,非CB1/CB2受体途径介导的神经保护活性及对脂肪酸酰胺水解酶活性的调节作用为该类化合物的重要特征。由于AEA作用于多靶点所致的许多副作用,给其临床试验和应用带来一定困难,而AEA类似物可能既具备AEA的神经保护活性又避免其毒副作用,因此研究AEA类似物的神经保护作用具有重要的理论意义和应用价值。本文主要对AEA及其类似物的神经保护活性和其作用机制进行综述。

Anandamide （AEA）,a kind of endocannabinoids,belongs to long-chain fatty acid derivatives and plays a critical neuroprotective role through cannabinoid receptor type 1/type 2（CB1/CB2）-dependent or CB1/CB2-independent pathways. In recent years,AEA analogs,including methylfluorophosphonate,fatty acid ethanolamides and lipoamino acids,have attracted considerable attention. AEA analogs have similar bioactivity and chemical structure as AEA,but their acting target and mechanism are different from AEA. AEA analogs may not only exhibit neuroprotective effects via CB1/CB2-independent pathway and inhibition of fatty acid amide hydrolase （FAAH）,but also avoid some side effects of AEA. For a better understanding of AEA and its analogs,this review briefly discusses their bioactivities and action mechanisms.