Shengli Clinical Medical College of Fujian Medical University, Department of Hepatobiliary and Pancreatic Surgery, Fujian Provincial Hospital, Fuzhou, Fujian, 350001, China.
Department of Pathology, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, 350001, China.
Adipocyte. 2021 Dec;10(1):532-545. doi: 10.1080/21623945.2021.1983241.
Verapamil can restore intracellular calcium homeostasis, increase the fusion of autophagosomes and lysosomes, reduce lipid droplet accumulation and inhibit inflammation and insulin resistance in high-fat-fed mice. The present study aimed to investigate verapamil's effect and its underlying liver regeneration mechanism in mice with non-alcoholic fatty liver. After 50% hepatectomy was performed, the changes of autophagy and liver regeneration were evaluated by detecting cell proliferation and autophagy at each time point. Then, 25mg/kg verapamil was injected intraperitoneally for 10 d before an operation in the mild to moderate fatty liver and severe fatty liver groups. The control group and mild to moderate fatty liver group reached the peak of proliferation at 24-48h after operation, and the mice with severe fatty liver and steatohepatitis reached the peak at 48-72h. Autophagy in the normal group and mild to moderate fatty liver group reached the peak 48 hours after operation. Verapamil injection can enhance autophagy, reduce the weight of fatty liver mice, improve liver function and liver regeneration. Verapamil can induce autophagy, improve hepatocyte function and promote hepatocyte regeneration through the mTOR independent signaling pathway, thus improving the process of liver regeneration after partial hepatectomy.
维拉帕米可恢复细胞内钙稳态，增加自噬体与溶酶体融合，减少脂滴堆积，并抑制高脂喂养小鼠的炎症和胰岛素抵抗。本研究旨在探讨维拉帕米对非酒精性脂肪肝小鼠的作用及其肝再生的潜在机制。行 50%肝切除术后，通过检测各时间点的细胞增殖和自噬来评估自噬和肝再生的变化。然后，在轻度至中度脂肪肝和重度脂肪肝组的手术前，经腹腔注射 25mg/kg 维拉帕米 10d。正常组和轻度至中度脂肪肝组在术后 24-48h 达到增殖高峰，重度脂肪肝和脂肪性肝炎组在术后 48-72h 达到高峰。正常组和轻度至中度脂肪肝组自噬在术后 48 小时达到高峰。维拉帕米注射可增强自噬，减轻脂肪肝小鼠的体重，改善肝功能和肝再生。维拉帕米可通过 mTOR 非依赖性信号通路诱导自噬，改善肝细胞功能并促进肝细胞再生，从而改善部分肝切除术后的肝再生过程。
