Avraham Y, Grigoriadis N C, Magen I, Poutahidis T, Vorobiav L, Zolotarev O, Ilan Y, Mechoulam R, Berry E M
Department of Metabolism and Human Nutrition, Braun School of Public Health, Hadassah-Hebrew University Medical School, Jerusalem, Israel.
Br J Pharmacol. 2009 Oct;158(3):896-906. doi: 10.1111/j.1476-5381.2009.00368.x. Epub 2009 Sep 18.
Hepatic encephalopathy is a neuropsychiatric syndrome caused by liver failure. In view of the effects of cannabinoids in a thioacetamide-induced model of hepatic encephalopathy and liver disease and the beneficial effect of capsaicin (a TRPV1 agonist) in liver disease, we assumed that capsaicin may also affect hepatic encephalopathy.
Fulminant hepatic failure was induced in mice by thioacetamide and 24 h later, the animals were injected with one of the following compound(s): 2-arachidonoylglycerol (CB(1), CB(2) and TRPV1 receptor agonist); HU308 (CB(2) receptor agonist), SR141716A (CB(1) receptor antagonist); SR141716A+2-arachidonoylglycerol; SR144528 (CB(2) receptor antagonist); capsaicin; and capsazepine (TRPV1 receptor agonist and antagonist respectively). Their neurological effects were evaluated on the basis of activity in the open field, cognitive function in an eight-arm maze and a neurological severity score. The mice were killed 3 or 14 days after thioacetamide administration. 2-arachidonoylglycerol and 5-hydroxytryptamine (5-HT) levels were determined by gas chromatography-mass spectrometry and high-performance liquid chromatography with electrochemical detection, respectively.
Capsaicin had a neuroprotective effect in this animal model as shown by the neurological score, activity and cognitive function. The effect of capsaicin was blocked by capsazepine. Thioacetamide induced astrogliosis in the hippocampus and the cerebellum and raised brain 5-hydroxytryptamine levels, which were decreased by capsaicin, SR141716A and HU-308. Thioacetamide lowered brain 2-arachidonoylglycerol levels, an effect reversed by capsaicin.
Capsaicin improved both liver and brain dysfunction caused by thioacetamide, suggesting that both the endocannabinoid and the vanilloid systems play important roles in hepatic encephalopathy. Modulation of these systems may have therapeutic value.
肝性脑病是一种由肝功能衰竭引起的神经精神综合征。鉴于大麻素在硫代乙酰胺诱导的肝性脑病和肝病模型中的作用，以及辣椒素（一种TRPV1激动剂）在肝病中的有益作用，我们推测辣椒素可能也会影响肝性脑病。
通过硫代乙酰胺诱导小鼠暴发性肝功能衰竭，24小时后，给动物注射以下化合物之一：2-花生四烯酸甘油酯（CB(1)、CB(2)和TRPV1受体激动剂）；HU308（CB(2)受体激动剂），SR141716A（CB(1)受体拮抗剂）；SR141716A + 2-花生四烯酸甘油酯；SR144528（CB(2)受体拮抗剂）；辣椒素；以及分别作为TRPV1受体激动剂和拮抗剂的辣椒平。根据旷场活动、八臂迷宫中的认知功能和神经严重程度评分来评估它们的神经学效应。在给予硫代乙酰胺后3天或14天处死小鼠。分别通过气相色谱-质谱联用和高效液相色谱电化学检测法测定2-花生四烯酸甘油酯和5-羟色胺（5-HT）水平。
如神经学评分、活动和认知功能所示，辣椒素在该动物模型中具有神经保护作用。辣椒素的作用被辣椒平阻断。硫代乙酰胺诱导海马体和小脑中的星形胶质细胞增生，并提高脑5-羟色胺水平，而辣椒素、SR141716A和HU - 308可使其降低。硫代乙酰胺降低脑2-花生四烯酸甘油酯水平，辣椒素可逆转这一效应。
辣椒素改善了由硫代乙酰胺引起的肝脏和脑功能障碍，表明内源性大麻素系统和香草酸受体系统在肝性脑病中均起重要作用。调节这些系统可能具有治疗价值。
