实用医学杂志 ›› 2026, Vol. 42 ›› Issue (3): 455-462.doi: 10.3969/j.issn.1006-5725.2026.03.013
• 慢性病防治专栏 • 上一篇
薛廷政1,梁凤霞1,2(
),黄柳杨1,2,王雅媛1,2,宋燕娟1,2
收稿日期:2025-07-28
出版日期:2026-02-10
发布日期:2026-02-09
通讯作者:
梁凤霞
E-mail:fxliang5@hotmail.com
基金资助:
Tingzheng XUE1,Fengxia LIANG1,2(
),Liuyang HUANG1,2,Yayuan WANG1,2,Yanjuan SONG1,2
Received:2025-07-28
Online:2026-02-10
Published:2026-02-09
Contact:
Fengxia LIANG
E-mail:fxliang5@hotmail.com
摘要:
沉默信息调节因子1(SIRT1)是一种高度保守的NAD+依赖性脱乙酰酶,不仅在脂肪组织中广泛表达,更在肥胖与胰岛素抵抗(IR)的发生发展中发挥关键作用。脂肪组织中的SIRT1通过抑制炎症反应、调节脂质代谢、促进脂肪褐变和血管生成,以及恢复胰岛素信号通路等多种机制,显著改善肥胖及相关代谢异常。靶向脂肪组织递送SIRT1激动剂白藜芦醇(Res)可进一步增强其对肥胖和IR的治疗效果。本文系统概述了SIRT1的分子结构基础及其在多器官中的作用,深入梳理了其在脂肪组织中多靶点调控肥胖与IR的分子网络,并总结了以Res为代表的SIRT1激动剂的不同脂肪靶向递送策略,以期为代谢性疾病的治疗提供新视角与研究思路。
中图分类号:
薛廷政,梁凤霞,黄柳杨,王雅媛,宋燕娟. 脂肪中SIRT1调控肥胖和胰岛素抵抗的研究进展及靶向治疗策略[J]. 实用医学杂志, 2026, 42(3): 455-462.
Tingzheng XUE,Fengxia LIANG,Liuyang HUANG,Yayuan WANG,Yanjuan SONG. Research progress and targeted therapeutic strategies of the SIRT1 pathway in adipose tissue for improving obesity and insulin resistance[J]. The Journal of Practical Medicine, 2026, 42(3): 455-462.
表1
白藜芦醇脂肪靶向递送系统差异分析表"
| 载体名称 | 靶向方式与特点 | 给药方案 | 与非靶向Res治疗比较的效果差异 | 参考文献 |
|---|---|---|---|---|
| 重组高密度脂蛋白(rHDL)+ 温敏水凝胶 | 主动靶向:ApoA-I模拟肽结合脂肪细胞SR-BI受体 特点:水溶性提高、缓释性提高、生物相容性好 | 方式:腹股沟皮下注射? 频次:每4 d 1次,持续24 d 剂量:未明确 | vs. Res+凝胶组?? 减脂效果更强:iWAT减少率从45.6%提升至68.2%?? 减重效果更强:体质量降低率从15% 提升至 27%?? 代谢改善更显著:大幅改善血糖、血脂及炎症状态 | [ |
| 传统脂质体 | 被动靶向:依赖EPR效应(增强渗透滞留) 特点:粒径100 nm、Zeta电位-25mV、水溶性提升30倍、缓释稳定 | 方式:iWAT局部注射? 频次:每周2次,持续5周 剂量:未明确 | vs. 游离Res处理组 肥胖指标改善更优:体质量、脂肪百分比、iWAT和gWAT质量多降低了1.2 ~ 1.6倍? 褐变能力更强:UCP1和TMEM26 mRNA水平多升高了1.8和2.6倍 | [ |
| 大豆磷脂酰胆碱脂质体 | 被动靶向:依赖脂质体天然亲和性? 特点:粒径(170 ± 6)nm、PDI < 0.2、包封率99.8%、水溶性提升100倍 | 方式:iWAT注射 频次:每周1次,持续4周 剂量:17.5 mg/kg/次 | vs. 游离Res处理组 ?? 产热与减脂效果更好:核心体温最高,体质量、体脂量及体脂百分比最低? 血糖调节功能更优 | [ |
| 配体修饰Res纳米颗粒? | 主动靶向:表面肽配体靶向ASCs的decorin受体 特点:主动靶向,减少肝积累,延长循环 | 方式:尾静脉注射? 频次:每2周1次,持续5周 剂量:52.5 mg/(kg·次) | vs. 游离Res处理组 ?? 靶向性更优:iWAT中Res含量更高,肝脏积累更少? 疗效更佳:诱导更多米色脂肪形成,在改善葡萄糖稳态、降低炎症及抗肥胖方面效果更显著 | [ |
| 靶向肽修饰纳米颗粒 | 主动靶向:用新一代ASC靶向肽修饰,特异性强、成本低 特点:高特异性主动靶向 | 方式:iWAT注射 频率:每2周1次,持续5周 剂量:30 mg/kg/次 | vs. 非靶向R-NPs组? ASC-1-R-NPs组:iWAT减少更显著,褐变基因Tmem26表达更高,并能改善胰岛素敏感性。 ASC-2-R-NPs组:治疗效果甚至高于ASC-1组 | [ |
| 羧甲基纤维素微针(MN)+离子电渗(INT) | 智能化经皮递送:ASC肽与药物共价偶联,INT增强渗透 特点:无创、局部递送高效 | 方式:iWAT区域皮肤贴敷? 频次:每周2次,持续4周 剂量:未明确 | vs.MN(游离Res)+INT组 (非靶向透皮组):?? 减重降脂效果更强:体质量和脂肪百分比降低幅度超1.5倍? 降糖效果更强:血糖水平降低幅度达1.4倍 褐变能力更强:UCP1的mRNA水平增加超3倍 | [ |
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