The First Clinical Medical College of Jinan University, Guangzhou, 510000, China.
Department of Health Supervision Center, the Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, China.
Biol Trace Elem Res. 2023 Aug;201(8):3971-3980. doi: 10.1007/s12011-022-03497-9. Epub 2023 Jan 5.
Aluminum (Al) exposure can lead to different degrees of damage to various organ systems of the body. It has been previously revealed that Al exposure can damage the liver, causing liver dysfunction. However, the specific mechanism remains unclear. This research aims to uncover the damaging effect of Al exposure on rat liver and to demonstrate the role of autophagy and apoptosis in this effect. Thirty-two Wistar rats were randomly divided into the control group (C group), low-dose Al exposure group (L group), middle-dose Al exposure group (M group), and high-dose Al exposure group (H group) (n = 8). The rats, respectively, received intraperitoneal injections of 0, 5, 10, and 20 mg/kg·day AlCl solution for 4 weeks (5 times/week). After the experiment, changes in the ultrastructure and autolysosome in rat liver were observed; the liver function, apoptosis rate, as well as levels of apoptosis-associated proteins and autophagy-associated proteins were detected. The results indicated that Al exposure damaged rat liver function and structure and resulted in an increase in autolysosomes. TUNEL staining revealed an elevated number of apoptotic hepatocytes after Al exposure. Moreover, we found from Western blotting that the levels of autophagy-associated proteins Beclin1 and LC3-II were increased; apoptotic protein Caspase-3 level was elevated and the Bcl-2/Bax ratio was reduced. Our research suggested that Al exposure can lead to high autophagy and apoptosis levels of rat hepatocytes, accompanied by hepatocyte injury and impaired liver function. This study shows that autophagy and apoptosis pathways participate in Al toxication-induced hepatocyte injury.
铝（Al）暴露可导致机体各器官系统不同程度的损伤。已有研究表明，铝暴露可损伤肝脏，导致肝功能异常。但其具体机制尚不清楚。本研究旨在揭示铝暴露对大鼠肝脏的损伤作用，并阐明自噬和凋亡在此过程中的作用。将 32 只 Wistar 大鼠随机分为对照组（C 组）、低剂量铝暴露组（L 组）、中剂量铝暴露组（M 组）和高剂量铝暴露组（H 组）（n=8）。分别给予大鼠腹腔注射 0、5、10、20mg/kg·day AlCl3 溶液，每周 5 次，共 4 周。实验结束后，观察大鼠肝脏超微结构和自噬溶酶体的变化，检测肝功能、凋亡率以及凋亡相关蛋白和自噬相关蛋白的水平。结果表明，铝暴露可损伤大鼠的肝功能和结构，导致自噬溶酶体增加。TUNEL 染色显示铝暴露后凋亡的肝细胞数量增加。此外，Western blot 结果显示自噬相关蛋白 Beclin1 和 LC3-II 水平升高，凋亡蛋白 Caspase-3 水平升高，Bcl-2/Bax 比值降低。研究提示，铝暴露可导致大鼠肝细胞高自噬和凋亡水平，同时伴有肝细胞损伤和肝功能障碍。本研究表明，自噬和凋亡途径参与了铝中毒诱导的肝细胞损伤。
