Yu Zhenfei, Li Ying, An Peng, Qian Xiaoling, Wang Yakun, Wang Bo
Dept Intens Care Unit, Hangzhou TCM Hospital affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
Special Inspection Division, Hangzhou TCM Hospital affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
Drug Dev Res. 2025 Aug;86(5):e70140. doi: 10.1002/ddr.70140.
Betulinic acid (BA) has the potential to ameliorate acute pancreatitis (AP); however, the mechanisms have not been fully elucidated. This study aimed to identify the effect of BA on mitophagy and its mediated acetylation. Rat pancreatic acinar AR42J cells were treated with cerulein to simulate AP-induced injury, and then inflammation and mitophagy were evaluated after BA treatment. The molecular mechanisms were analyzed using molecular docking, immunoprecipitation, immunoblotting, and cycloheximide chase assay. The roles of BA and SIRT1 in vivo were assessed by HE staining and enzyme-linked immunosorbent assay. The results showed that BA inhibited inflammation and promoted mitophagy in cerulein-induced AR42J cells. BA combined with SIRT1 and reduced SIRT1-mediated acetylation. Knockdown of SIRT1 counteracted the inflammation and mitophagy caused by BA. Moreover, interference with SIRT1 promoted acetylation of PINK1 to degrade PINK1 protein, which knockdown reversed the inhibition of inflammation and the promotion of mitophagy induced by SIRT1. Additionally, BA inhibited pancreatic tissue injury and inflammation levels in the pancreas in AP mice by regulating SIRT1. In conclusion, BA decelerates the progression of AP by promoting mitophagy and inhibiting inflammation in pancreatic acinar cells. Mechanically, BA increased SIRT1 expression, which knockdown degraded PINK1 protein by inducing acetylation of PINK1.
桦木酸（BA）具有改善急性胰腺炎（AP）的潜力；然而，其机制尚未完全阐明。本研究旨在确定BA对线粒体自噬及其介导的乙酰化作用的影响。用雨蛙肽处理大鼠胰腺腺泡AR42J细胞以模拟AP诱导的损伤，然后在BA处理后评估炎症和线粒体自噬。使用分子对接、免疫沉淀、免疫印迹和环己酰亚胺追踪试验分析分子机制。通过苏木精-伊红（HE）染色和酶联免疫吸附测定评估BA和沉默信息调节因子1（SIRT1）在体内的作用。结果表明，BA在雨蛙肽诱导的AR42J细胞中抑制炎症并促进线粒体自噬。BA与SIRT1结合并减少SIRT1介导的乙酰化。敲低SIRT1可抵消BA引起的炎症和线粒体自噬。此外，干扰SIRT1促进PTEN诱导激酶1（PINK1）的乙酰化以降解PINK1蛋白，敲低可逆转SIRT1诱导的炎症抑制和线粒体自噬促进。此外，BA通过调节SIRT1抑制AP小鼠胰腺组织损伤和胰腺炎症水平。总之，BA通过促进胰腺腺泡细胞中的线粒体自噬和抑制炎症来减缓AP的进展。机制上，BA增加SIRT1表达，敲低通过诱导PINK1乙酰化降解PINK1蛋白。
