Abstract：
Trimethyltin chloride (TMT) is a highly toxic organotin compound often used in plastic heat stabilizers, chemical pesticides, and wood preservatives. TMT accumulates mainly through the environment and food chain. Exposure to organotin compounds is associated with disorders of glucolipid metabolism and obesity. The mechanism by which TMT damages pancreatic tissue is unclear. For this purpose, a subacute exposure model of TMT was designed for this experiment to study the mechanism of damage by TMT on islet. The fasting blood glucose and blood lipid content of mice exposed to TMT were significantly increased. Histopathological and ultrastructural observation and analysis showed that the TMT-exposed group had inflammatory cell infiltration and necrosis. Then, mouse pancreatic islet tumour cells (MIN-6) were treated with TMT. Autophagy levels were detected by fluorescence microscopy. Real-time quantitative polymerase chain reaction and Western blotting were used for verification. A large amount of autophagy occurred at a low concentration of TMT but stagnated at a high concentration. Excessive autophagy activates apoptosis when exposed to low levels of TMT. With the increase in TMT concentration, the expression of necrosis-related genes increased. Taken together, different concentrations of TMT induced apoptosis and necrosis through autophagy disturbance. TMT impairs pancreatic (islet β cell) function.
摘要：
三甲基氯化锡（TMT）是一种剧毒的有机锡化合物，常用于塑料热稳定剂，化学农药,和木材防腐剂。TMT主要通过环境和食物链积累。暴露于有机锡化合物与糖脂代谢障碍和肥胖有关。TMT损伤胰腺组织的机制尚不清楚。为此,本实验设计了TMT亚急性暴露模型，以研究TMT对胰岛的损伤机制。暴露于TMT的小鼠的空腹血糖和血脂含量明显升高。组织病理学和超微结构观察分析显示TMT暴露组有炎性细胞浸润和坏死。然后，用TMT处理小鼠胰岛肿瘤细胞(MIN-6)。荧光显微镜检测自噬水平。使用实时定量聚合酶链反应和Western印迹进行验证。在低浓度的TMT时发生了大量的自噬，但在高浓度时停滞。当暴露于低水平的TMT时，过度的自噬激活细胞凋亡。随着TMT浓度的增加,坏死相关基因的表达增加。一起来看,不同浓度的TMT通过自噬干扰诱导细胞凋亡和坏死。TMT损害胰腺(胰岛β细胞)功能。
