Page 81 - 《中国药科大学学报》2025年第4期

第 56 卷第 4 期 郭光耀，等：PPARβ 激动剂 ZLY16 促进肌再生及改善 mdx 小鼠运动能力 477

factor-β，TGF-β1）并伴随细胞外基质（extracellular Biomolecules, 2022, 12(12): 1832.
[9] Shi YJ, Zou YX, Shen ZY, et al. Trace elements, PPARs, and
matrix，ECM）蛋白过度合成与沉积，使得骨骼肌纤
metabolic syndrome[J]. Int J Mol Sci, 2020, 21(7): 2612.
[22]
维化不断加重，导致肌再生障碍 。有研究表明， [10] Bell EL, Shine RW, Dwyer P, et al. PPARδ modulation rescues
PPARβ 具有直接的抗纤维化作用，如 PPARβ 激动 mitochondrial fatty acid oxidation defects in the mdx model of
剂 Seladelpar 通过抑制新胶原蛋白合成速率，降低 muscular dystrophy[J]. Mitochondrion, 2019, 46: 51-58.
[11] Zhou ZT, Deng LM, Hu LJ, et al. Hepatoprotective effects of
肝纤维化，从而治疗小鼠非酒精性脂肪性肝炎 。 ZLY16, a dual peroxisome proliferator-activated receptor α/δ
[23]
本研究发现在 mdx 小鼠中，ZLY16 抗肌纤维化的 agonist, in rodent model of nonalcoholic steatohepatitis[J]. Eur
效果要优于辛伐他汀，这提示 PPARβ 激动剂具有 J Pharmacol, 2020, 882: 173300.
[12] Fan WW, Waizenegger W, Lin CS, et al. PPARδ promotes run-
在骨骼肌纤维化相关疾病中应用的前景。 ning endurance by preserving glucose[J]. Cell Metab, 2017,
本研究发现 ZLY16 能够抑制骨骼肌中炎性细 25(5): 1186-1193. e4.
胞浸润，缓解肌纤维坏死，表明 ZLY16 具有一定的 [13] Aguilar-Recarte D, Barroso E, Gumà A, et al. GDF15 mediates
the metabolic effects of PPARβ/δ by activating AMPK[J]. Cell
抗炎作用，后期与糖皮质激素联用可能会达到更好 Rep, 2021, 36(6): 109501.
的治疗效果。此外，本研究还发现与对照组相比， [14] Whitehead NP, Kim MJ, Bible KL, et al. A new therapeutic ef-
辛伐他汀可以降低 PPARβ 表达，这可能是因为辛 fect of simvastatin revealed by functional improvement in mus-
cular dystrophy[J]. Proc Natl Acad Sci U S A, 2015, 112(41):
伐他汀先通过减少纤维化、抑制炎症，然后减少脂 12864-12869.
质蓄积 ，从而使得反馈式 PPAR 表达水平降低。 [15] Srivastava NK, Yadav R, Mukherjee S, et al. Abnormal lipid
[14]
综上，本研究发现了新型 PPARβ 激动剂 ZLY16 metabolism in skeletal muscle tissue of patients with muscular
dystrophy: in vitro, high-resolution NMR spectroscopy based
可以缓解高脂环境下成肌细胞分化障碍，可以减少 observation in early phase of the disease[J]. Magn Reson Imag-
mdx 小鼠体内脂质蓄积，促进骨骼肌再生，从而改 ing, 2017, 38: 163-173.
[16] Samani A, Karuppasamy M, English KG, et al. DOCK3 regu-
善其运动能力。ZLY16 有望成为治疗 DMD 的新
lates normal skeletal muscle regeneration and glucose
药物，也将为后期开发更多用于治疗 DMD 的 PPAR metabolism[J]. FASEB J, 2023, 37(10): e23198.
激动剂提供参考。 [17] Bojic LA, Telford DE, Fullerton MD, et al. PPARδ activation
attenuates hepatic steatosis in Ldlr-/- mice by enhanced fat oxi-
dation, reduced lipogenesis, and improved insulin sensitivity[J].
J Lipid Res, 2014, 55(7): 1254-1266.
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