Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Exercise Physiology, Faculty of Sports Sciences, University of Mazandaran, Mazandaran, Iran.
Mol Biol Rep. 2024 Aug 22;51(1):928. doi: 10.1007/s11033-024-09844-4.
There is a need for effective treatments for non-alcoholic fatty liver disease (NAFLD) that are economically inexpensive, and have few side effects. The present study aimed to investigate exercise training and silymarin on hepatocyte death factors in rats with liver damage.
Forty-nine male Wistar rats were assigned to seven groups: sedentary control, fatty liver control (DEX), fatty liver + high-intensity interval training (HIIT), fatty liver + HIIT + silymarin (HIIT + SILY), fatty liver + continuous training (CT), fatty liver + CT + silymarin (CT + SILY), and fatty liver + silymarin (SILY). A subcutaneous injection of dexamethasone for 7 days was used to induce fatty liver in rats. Masson's trichrome and hematoxylin-eosin staining were done to evaluate hepatic injury. The hepatocyte apoptosis was determined by TUNEL assay. Real-Time PCR was conducted to evaluate the gene expressions of caspase-9, adenosine monophosphate-activated protein kinase (AMPKα1), mitofusin 2 (Mfn2), and damage-regulated autophagy modulator (DRAM). Liver tissue changes and serum levels of liver enzymes were also evaluated.
Liver apoptosis was decreased in the CT, HIIT, HIIT + SILY and CT + SILY groups compared to the DEX group. Both continuous and high-intensity training models produced beneficial alterations in liver morphology and hepatic injuries that were significant in exercise training + silymarin group. This impact was accompanied by increased AMPKα1 and DRAM gene expression and decreased caspase-9 and Mfn2 gene expression. Liver enzyme levels were high in the DEX group and treatment with silymarin significantly reduced it.
Silymarin supplementation combined with interval or continuous training substantially improves DEX-induced hepatic steatosis and hepatocyte injury mostly through suppressing liver apoptosis and upregulating autophagy, which may provide a novel perspective for NAFLD treatment.
需要寻找一种有效、经济实惠且副作用小的非酒精性脂肪性肝病（NAFLD）治疗方法。本研究旨在探讨运动训练和水飞蓟素对肝损伤大鼠肝细胞死亡因子的影响。
将 49 只雄性 Wistar 大鼠分为 7 组：安静对照组、脂肪肝对照组（DEX）、脂肪肝+高强度间歇训练组（HIIT）、脂肪肝+HIIT+水飞蓟素组（HIIT+SILY）、脂肪肝+持续训练组（CT）、脂肪肝+CT+水飞蓟素组（CT+SILY）和脂肪肝+水飞蓟素组（SILY）。通过皮下注射地塞米松 7 天诱导大鼠脂肪肝。采用 Masson 三色和苏木精-伊红染色评估肝损伤，TUNEL 法检测肝细胞凋亡，实时 PCR 检测半胱氨酸天冬氨酸蛋白酶-9（caspase-9）、腺苷单磷酸激活蛋白激酶（AMPKα1）、线粒体融合蛋白 2（Mfn2）和损伤调节自噬调节剂（DRAM）的基因表达。还评估了肝组织变化和血清肝酶水平。
与 DEX 组相比，CT、HIIT、HIIT+SILY 和 CT+SILY 组的肝凋亡减少。连续和高强度训练模型均对肝形态和肝损伤产生有益的改变，在运动训练+水飞蓟素组中更为显著。这种影响伴随着 AMPKα1 和 DRAM 基因表达的增加以及 caspase-9 和 Mfn2 基因表达的减少。DEX 组的肝酶水平较高，水飞蓟素治疗显著降低了其水平。
水飞蓟素补充剂联合间歇或持续训练可显著改善 DEX 诱导的肝脂肪变性和肝细胞损伤，主要通过抑制肝凋亡和上调自噬来实现，这为 NAFLD 的治疗提供了新的视角。
