TY -的T1 Silybin恢复CYP3A表达式通过Sirtuin蛋白2 /核因子κ- b途径在小鼠非酒精性脂肪肝病JF -药物代谢和性格乔-药物金属底座Dispos SP - 770 LP - 779 - 10.1124 / dmd.121.000438六世- 49 - 9盟张盟——徐雷竞技客服,丹盟——张Yirui AU -王,瑞盟-杨,Na AU -卢,Yunge盟——赵Haokai AU - Aa,胡继晔AU - Wang Guangji盟,谢元Y1 - 2021/09/01 UR - //www.1zgc.com/content/49/9/770.abstract N2 - Silybin被广泛用作王亚南代理各种肝脏疾病的治疗方法,已被确认为CYP3A抑制剂。然而，水飞蓟宾对CYP3A的影响及在高脂饮食(HFD)诱导的肝脏炎症中的调控机制尚不清楚。在我们的研究中，我们发现水飞蓟宾恢复了被HFD和条件培养基(CM)抑制的CYP3A的表达和活性。此外，水飞蓟宾通过提高SIRT2表达和促进p65去乙酰化抑制了高脂喂养小鼠的肝脏炎症反应，并抑制核因子κ b向核内转移。这一作用通过过表达SIRT2得到证实，SIRT2抑制了p65的核易位，并恢复了CM影响下CYP3A的转录。NAD+在高脂喂养小鼠和cm处理的肝细胞/HepG2细胞中显著降低，水飞蓟宾处理后升高。在HepG2细胞和小鼠肝细胞中，补充烟酰胺单核苷酸作为NAD+供体可抑制p65乙酰化，减少p65核易位，并恢复cyp3a转录。这些结果表明，水飞蓟宾通过一种与NAD+和SIRT2水平升高相关的机制调节肝脏炎症过程中的代谢酶。水飞蓟宾通过降低多聚adp核糖聚合酶-1的表达，提高了细胞内NAD+的浓度。 In summary, silybin increased NAD+ concentration, promoted SIRT2 expression, and lowered p65 acetylation both in vivo and in vitro, which supported the recovery of CYP3A expression. These findings indicate that the NAD+/SIRT2 pathway plays an important role in CYP3A regulation during nonalcoholic fatty liver disease.SIGNIFICANCE STATEMENT This research revealed the differential regulation of CYP3A by silybin under physiological and fatty liver pathological conditions. In the treatment of nonalcoholic fatty liver disease, silybin restored, not inhibited, CYP3A expression and activity through the NAD+/ sirtuin 2 pathway in accordance with its anti-inflammatory effect. ER -