棕榈酸乙醇酰胺 (PEA) 通过 PPARα 抑制经典和非经典 TGFβ 信号通路，减少兔实验性斜视手术后的粘连。

Palmitoylethanolamide (PEA) reduces postoperative adhesions after experimental strabismus surgery in rabbits by suppressing canonical and non-canonical TGFβ signaling through PPARα.

机构信息

Affiliated Xiamen Eye Center, Xiamen University, Xiamen 361005, China; Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, Xiamen 361102, China.

Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, Xiamen 361102, China.

出版信息

Biochem Pharmacol. 2021 Feb;184:114398. doi: 10.1016/j.bcp.2020.114398. Epub 2020 Dec 30.

DOI:10.1016/j.bcp.2020.114398

PMID:33385371

Abstract

Postoperative adhesions and scarring are the particular complication after strabismus surgery, for which there is currently no comprehensive treatment available. Preventing inflammation and fibrosis in the extraocular muscle are crucial for treatment of postoperative adhesions. In the present study, we found that administration of palmitoylethanolamide (PEA) attenuated postoperative inflammation and fibroproliferation through activating peroxisome proliferator-activated receptor α (PPARα), thus prevented scar formation. Inhibition of PEA degradation by N-Acylethanolamine acid amidase (NAAA) inhibitor F96 led to the same pharmacological results. PPARα activation suppressed both canonical and non-canonical TGFβ signaling. Mechanistically, we found that PPARα directly bound to TGFβ-activated kinase 1 (TAK1), thus preventing its hyperphosphorylation and the activation of downstream p38 and JNK1/2 signaling. Taken together, current study suggested that PEA could be a novel therapeutic approach for postoperative adhesions after strabismus surgery.

摘要

术后粘连和瘢痕形成是斜视手术后的特殊并发症，目前尚无全面的治疗方法。预防眼外肌的炎症和纤维化对于治疗术后粘连至关重要。在本研究中，我们发现棕榈酸乙醇酰胺（PEA）通过激活过氧化物酶体增殖物激活受体α（PPARα）减轻术后炎症和纤维增生，从而防止瘢痕形成。N-酰基乙醇胺酸酰胺酶（NAAA）抑制剂 F96 抑制 PEA 的降解可产生相同的药理作用。PPARα 的激活抑制了经典和非经典 TGFβ 信号通路。在机制上，我们发现 PPARα 直接与 TGFβ 激活激酶 1（TAK1）结合，从而阻止其过度磷酸化和下游 p38 和 JNK1/2 信号的激活。综上所述，本研究表明 PEA 可能是斜视手术后术后粘连的一种新的治疗方法。