目的探讨雌激素对脓毒症所致肝损伤的保护作用,及这种作用是否与自噬表达增加有关。方法建立正常雄性、雌性及给予外源性雌激素的雄性小鼠毒血症模型,比较三组间肝功能变化、自噬表达以及小鼠病死率,HE染色观察肝脏病理学形态;并行电镜、免疫组化及Western blotting检测自噬蛋白的变化。结果丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平雌性组显著低于雄性组,且两组显著高于给予外源性雌激素的雄性组。HE染色显示雄性组肝损伤较雌性组重,且给予外源性雌激素的雄性组损伤最轻。电镜下雌性组观察到的自噬体数多于雄性组,给予外源性雌激素的雄性组最多。Western blotting检测显示自噬蛋白在给予外源性雌激素的雄性组表达最高,雌性组次之,雄性组表达最低。免疫组化检测结果类似Western blotting结果。小鼠病死率雌性组低于雄性组,且两组均高于给予外源性雌激素的雄性组。结论雌激素可能会通过诱导自噬减轻毒血症造成的肝脏损伤,该结果为治疗提供了新的临床思路。
Objective To explore the protective effect of estrogen in a sepsis-induced liver injury, and if the effect is associated with an increased autophagy expression. Methods The three sepsis models were male mice (M), female mice (FM), and male mice given 1713-estradiol (M-EG). The three groups were then monitored specifically for liver function, the expression of autophagy protein, and mortality. The results from the three groups were compared. HE staining observed the hepatic tissue pathology and the expression of autophagy protein was detected by electron microscope, immunohistochemistry and Western blotting. Results For ALT and AST, the values of the FM group were significantly lower than the M group, and the values of the M and FM groups were significantly higher than the M-EG group. For HE, the liver damage was heavier in the M group than in the FM group, and it was the lightest in the M-EG group. For the electron microscope, there were less autophagosomes found in the M group compared with the FM group, and the most autophagosomes were observed in the M-EG group. In Western blotting, the expression of autophagy protein was the highest in the M-EG group, and it was higher in the FM group compared with the M group. In immunohistochemistry, the expression of autophagy protein was higher in the FM group compared with the M group, and it was the highest in the M-EG group. For mortality, the values o{ the FM group were significantly lower than the M group, and it was the lowest in the M-EG group. Conclusion Estrogen may induce autophagy to protect the liver from injury due to sepsis in mice, and this provides new clinical ideas for potential therapy.