Cannabinoids and Capsaicin Improve Liver Function Following Thioacetamide-Induced Acute Injury in Mice
Cannabinoids and Capsaicin Improve Liver Function Following Thioacetamide-Induced Acute Injury in Mice
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DOI：
10.1111/j.1572-0241.2008.02155.x
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发表时间：
2008-12-01
影响因子：
9.8
通讯作者：
Berry, Elliot M.
中科院分区：
文献类型：
--
作者：
Avraham, Yosefa;Zolotarev, Olga;Berry, Elliot M.
目的：我们已经在硫乙酰胺引起的肝性脑病小鼠模型中显示了大麻素的有益作用，现在报告它们对肝损伤的影响。方法：采用200mg /kg硫代乙酰胺诱导野生型（WT）和CB2敲除型（KO）小鼠暴发性肝衰竭（FHF）。24小时后，小鼠注射2-花生四烯酮甘油（CB1、CB2和TRPV1激动剂）、HU308 （CB2激动剂）、SR141716 A （CB1受体阻滞剂）、SR141716 A+2-AG和SR144528 （CB2受体阻滞剂）、辣椒素和辣椒素（TRPV1激动剂和拮抗剂受体）。给药后第2天（第3天）处死小鼠，肝组织进行肝脏生化、组织病理学检查和2-花生四烯醇甘油水平测定。结果：用硫乙酰胺治疗48 h后，肝脏组织病理学显示坏死和炎症。SR141716 A、HU308和2-花生四烯醇甘油在给药后1天减轻炎症并促进再生。硫乙酰胺给药后肝酶升高，单独或联合使用sr141716a和2-花生四烯醇甘油（HU-308）后肝酶逆转，但SR144528没有。因此，通过CB2受体介导的有益作用。然而，CB2 KO小鼠仍然通过TRPV1受体调节肝功能。辣椒素改善了WT硫代乙酰胺处理小鼠的肝脏病理和功能，而辣椒平则使其受损。结论：大麻素及其拮抗剂对脑和肝脏的作用模式相似，表明其治疗效果可能是通过CB2受体和/或TRPV1受体改善这两个器官的。调节这些系统可能具有治疗潜力。[J] .中华胃肠病杂志，2008;43(3):347 - 356。
OBJECTIVES: We have shown the beneficial effects of cannabinoids in a murine model of hepatic encephalopathy following thioacetamide and now report their effects on the liver injury.METHODS: Fulminant hepatic failure (FHF) was induced by administration of 200 mg/kg thioacetamide to wild-type (WT) and CB2 Knockout (KO) mice. Twenty-four hours later, mice were injected with 2-arachidonoylglycerol (CB1, CB2, and TRPV1 agonist), HU308 (CB2 agonist), SR141716 A (CB1 receptor blocker), SR141716 A+2-AG, and SR144528 (CB2 receptor blocker), capsaicin and capsazepine (TRPV1 agonist and antagonist receptors). Mice were sacrificed 2 days after thioacetamide administration (day 3) and liver biochemistry and histopathology as well as evaluation of 2-arachidonoylglycerol levels were performed on liver tissue.RESULTS: Liver histopathology undertaken 48 h after thioacetamide showed evidence of necrosis and inflammation. SR141716 A, HU308, and 2-arachidonoylglycerol reduced inflammation and promoted regeneration 1 day after their administration.Liver enzymes increased after thioacetamide administration and were reversed after SR141716 A and 2-arachidonoylglycerol administered alone or combined, HU-308, but not SR144528. Thus, the beneficial effects mediated through CB2 receptors. However, CB2 KO mice still modulated liver function via the TRPV1 receptors. Capsaicin improved both liver pathology and function in WT thioacetamide-treated mice, while capsazepine impaired it.CONCLUSIONS: The similar pattern found between the effect of cannabinoids and their antagonists on brain and liver indicated that the therapeutic effect might be directed by the improvement in both organs through CB2 receptors and/or TRPV1 receptors. Modulation of these systems may have therapeutic potential.(Am J Gastroenterol 2008;103:3047-3056).