Purine signaling pathway plays an important role in inflammation and tissue damage. To investigate the role of purine signaling pathway in acute alcoholic liver injury and chronic alcoholic liver fibrosis, we replicated two animal models and two cellular models. We found that body weights, liver indexes, serum biochemical parameters, serum fibrosis indexes, and pathological and immunohistochemical results had significant changes in two treatment groups compared with two control groups. In addition, gene expressions of purine receptors, inflammatory cytokines, fibrogenic cytokines, and inflammasomes increased obviously in two animal models and two cellular models. Furthermore, purine receptor inhibitors could significantly inhibit protein expressions of purine receptors and reduce protein expressions of inflammatory cytokines, fibrogenic cytokines, and inflammasomes. Besides, P2X7R small interfering ribonucleic acid (siRNA) had the same effects. Meanwhile, we detected protein expressions of inflammatory cytokines secreted by inflammasomes, and we found that purine receptor-mediated inflammasomes activation was a key event in the process of chronic alcoholic liver fibrosis. In summary, this study shows that inhibition of purine receptors can alleviate acute alcoholic liver injury and chronic alcoholic liver fibrosis in mice. Therefore, purine receptor is a potential new target for the treatment of acute alcoholic liver injury and chronic alcoholic fibrosis.

中文翻译：

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嘌呤信号调节 HSCs 炎性细胞因子的分泌、活化和增殖在酒精性肝病中起关键作用。

嘌呤信号通路在炎症和组织损伤中起重要作用。为了研究嘌呤信号通路在急性酒精性肝损伤和慢性酒精性肝纤维化中的作用，我们复制了两种动物模型和两种细胞模型。我们发现，与两个对照组相比，两个治疗组的体重、肝脏指标、血清生化指标、血清纤维化指标以及病理和免疫组化结果都有显着变化。此外，在两种动物模型和两种细胞模型中，嘌呤受体、炎性细胞因子、纤维化细胞因子和炎性体的基因表达明显增加。此外，嘌呤受体抑制剂可显着抑制嘌呤受体蛋白表达，降低炎性细胞因子、纤维化细胞因子、和炎症小体。此外，P2X7R 小干扰核糖核酸（siRNA）也有同样的效果。同时，我们检测了炎症小体分泌的炎性细胞因子的蛋白表达，发现嘌呤受体介导的炎症小体激活是慢性酒精性肝纤维化过程中的关键事件。综上所述，本研究表明抑制嘌呤受体可减轻小鼠急性酒精性肝损伤和慢性酒精性肝纤维化。因此，嘌呤受体是治疗急性酒精性肝损伤和慢性酒精性纤维化的潜在新靶点。我们发现嘌呤受体介导的炎症小体激活是慢性酒精性肝纤维化过程中的关键事件。综上所述，本研究表明抑制嘌呤受体可减轻小鼠急性酒精性肝损伤和慢性酒精性肝纤维化。因此，嘌呤受体是治疗急性酒精性肝损伤和慢性酒精性纤维化的潜在新靶点。我们发现嘌呤受体介导的炎症小体激活是慢性酒精性肝纤维化过程中的关键事件。综上所述，本研究表明抑制嘌呤受体可减轻小鼠急性酒精性肝损伤和慢性酒精性肝纤维化。因此，嘌呤受体是治疗急性酒精性肝损伤和慢性酒精性纤维化的潜在新靶点。