PDF(Pubmed)
Abstract：
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world, which begins with liver lipid accumulation and is associated with metabolic syndrome. Also, the name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). We performed focused drug screening and found that Cilostazol effectively ameliorated hepatic steatosis and might offer potential for NAFLD treatment. Our aim was to investigate the therapeutic effects of Cilostazol on the glycolipid metabolism and intestinal flora in NAFLD mice and explore the specific mechanism. In this study, 7-week-old male C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD, and then treated with intragastric administration for 12 weeks. The results showed that Cilostazol inhibited liver lipid de novo synthesis by regulating the AMPK-ACC1/SCD1 pathway and inhibited liver gluconeogenesis by the AMPK-PGC1α-G6P/PEPCK pathway. Cilostazol improved the intestinal flora diversity and intestinal microbial composition in the NAFLD mice, and specifically regulated Desulfovibrio and Akkermansia. In addition, Cilostazol increased the level of short-chain fatty acids in the NAFLD mice to a level similar to that in the blank Control group. Cilostazol reduces liver lipid accumulation in NAFLD mice by improving glucose and lipid metabolism disorders and intestinal dysfunction, thereby achieving the purpose of treating NAFLD.
摘要：
非酒精性脂肪性肝病(NAFLD)是世界上最常见的慢性肝病之一。从肝脏脂质积累开始，并与代谢综合征有关。此外，选择替代NAFLD的名称是代谢功能障碍相关脂肪变性肝病(MASLD).我们进行了重点药物筛选，发现西洛他唑可有效改善肝性脂肪变性，并可能为NAFLD治疗提供潜力。本研究旨在探讨西洛他唑对NAFLD小鼠糖脂代谢和肠道菌群的治疗作用及其机制。在这项研究中,7周龄雄性C57BL/6J小鼠饲喂高脂饮食（HFD）8周以诱导NAFLD，然后用灌胃给药治疗12周。结果表明，西洛他唑通过调节AMPK-ACC1/SCD1途径抑制肝脏脂质从头合成，通过AMPK-PGC1α-G6P/PEPCK途径抑制肝脏糖异生。西洛他唑改善NAFLD小鼠肠道菌群多样性和肠道微生物组成,并特别调节Desulfovibrio和Akkermansia。此外,西洛他唑将NAFLD小鼠的短链脂肪酸水平提高到与空白对照组相似的水平。西洛他唑通过改善糖脂代谢紊乱和肠道功能紊乱,降低NAFLD小鼠肝脏脂质蓄积,从而达到治疗NAFLD的目的。
