色氨酸羟化酶1在代谢相关脂肪性肝病中的作用机制研究进展  

The role of tryptophan hydroxylase 1 in the mechanisms of metabolism-associated fatty liver disease and potential therapeutic targets

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作  者:贾双珍(综述) 吴捷(审校) Jia Shuangzhen;Wu Jie(Department of Gastroenterology,Beijing Children's Hospital,Capital Medical University,National Center for Children's Health,Beijing 100045,China)

机构地区:[1]国家儿童医学中心/首都医科大学附属北京儿童医院消化科,100045

出  处:《疑难病杂志》2025年第4期499-502,共4页Chinese Journal of Difficult and Complicated Cases

基  金:北京市医院管理中心“登峰”人才培养计划(DFL 20221003)。

摘  要:代谢相关脂肪性肝病(MAFLD)是一种与代谢功能紊乱相关的慢性肝脏疾病,其发病多与肥胖、胰岛素抵抗、脂代谢紊乱等有关,但具体发病机制尚未完全阐明。色氨酸羟化酶1(TPH1)属于羟化酶类,参与色氨酸代谢途径中的关键步骤,从而发挥生物学功能。近年来,研究发现TPH1及其合成的5-羟色胺(5-HT)与MAFLD的发生发展存在关联,TPH1合成5-HT,可抑制线粒体自噬,诱导肝脏脂质聚集、氧化应激和炎性反应增加,从而推动MAFLD进展。因此,抑制TPH1可能成为MAFLD潜在的治疗靶点。文章对TPH1在MAFLD中的作用机制进行综述,重点分析其对线粒体自噬的影响,并探讨TPH1抑制剂在MAFLD中的治疗前景,以期开发和制定个性化治疗策略。Metabolic-associated fatty liver disease(MAFLD)is a chronic liver disease associated with metabolic dysfunction,and its onset is mostly correlated with obesity,insulin resistance and lipid metabolism disorders.However,the specific pathogenesis has not been fully elucidated.Tryptophan hydroxylase 1(TPH1)belongs to hydroxylase,which participates in the key step in tryptophan metabolism and thus plays biological function.In recent years,studies have found that TPH1 and its synthesized 5-hydroxytryptamine(5-HT)are correlated with the occurrence and development of MAFLD.The synthesis of 5-HT by TPH1 can inhibit mitochondrial autophagy,induce liver lipid aggregation,oxidative stress and inflammation aggravation,and thus promote MAFLD.Therefore,inhibiting TPH1 may be a potential therapeutic target for MAFLD.This research will review action mechanism of TPH1 in MAFLD,emphatically analyze its influences on mitochondrial autophagy and explore therapeutic prospects of TPH1 inhibitors in MAFLD so as to develop personalized treatment strategies for MAFLD.

关 键 词:代谢相关脂肪性肝病 色氨酸羟化酶1 5-羟色胺 线粒体自噬 作用机制 

分 类 号:R575.5[医药卫生—消化系统]

 

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