塞马格卢提德对Ldlr-/-.Leiden小鼠的非酒精性脂肪肝炎有有益影响
José A Inia1,2,3, Geurt Stokman1, Martine C Morrison1
1Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), 2333 BE Leiden, The Netherlands.
International journal of molecular sciences
|May 27, 2023
概括
塞马格卢提德有效治疗肥胖症,并显示出对非酒精性脂肪肝炎 (NASH) 的承诺. 在小鼠中,它减少了肝脏脂肪和炎症,但没有逆转晚期纤维化,这表明可能需要组合治疗.
科学领域:
- 肝病学和内分泌学.
- 代谢疾病 代谢疾病
- 药理学 药理学是指药理学的学科.
背景情况:
- 作为GLP-1受体激动剂的塞马格卢提德,已被批准用于糖尿病和肥胖症.
- 新出现的证据表明,塞马格卢提德在治疗非酒精性脂肪肝炎 (NASH) 中具有潜力.
研究的目的:
- 为了评估semaglutide在先进的NASH转化小鼠模型中的疗效.
- 评估塞马格卢提德对肝硬化,炎症,纤维化和动脉样硬化的影响.
主要方法:
- Ldlr-/-.Leiden小鼠被食快餐饮食 (FFD) 25周,接下来是12周的FFD,用semaglutide或载体.
- 评估了血参数,肝脏和心脏组织,并进行了肝脏转录组分析.
- 利用数字病理学进行原纤维评估,并将小鼠转录组与人类NASH基因组进行比较.
主要成果:
- 赛马格卢提德显著降低了宏观 (-74%) 和微观 (-100%) 肥胖症和肝炎 (-73%).
- 在组织学上没有观察到肝纤维化显著改善,但数字病理学表明原纤维网膜减少 (-12%).
- 塞马格卢提德没有影响动脉样硬化,并且逆转了与人类NASH纤维化相关的基因表达特征.
结论:
- 塞马格卢提德在晚期纳氏淋病中显示出肝硬化症和炎症的显著治疗潜力.
- 晚期纤维化的逆转可能需要与其他药物的联合治疗.
- 塞马格卢提德的转录效应与在纳氏血栓炎患者中观察到的改善相一致.
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