高铜诱导大鼠卵巢自噬发生

Autophagy of ovary in rats induced by high dietary copper

为探讨高铜对大鼠卵巢的影响,将24只20日龄大鼠随机分成4个不同浓度CuCl2饲料饲喂组:对照组(15 mg/kg)、高铜Ⅰ组(30 mg/kg)、高铜Ⅱ组(60 mg/kg)和高铜Ⅲ组(120 mg/kg),连续饲喂6个月。观察卵巢病理变化,检测血浆和卵巢铜含量、抗氧化指标(SOD活性、MDA含量、T-AOC水平)、自噬相关基因(LC3-Ⅰ、LC3-Ⅱ、Atg-5、Beclin-1)表达和自噬蛋白LC3-Ⅱ定位表达。结果显示,随着饲料铜含量增高,卵巢中铜含量呈升高趋势,高铜组大鼠卵巢出现卵泡闭锁和颗粒细胞扩散;卵巢组织中MDA含量、T-AOC水平和SOD活力均明显升高(P<0.05);卵巢中自噬相关基因LC3-Ⅰ、LC3-Ⅱ、Atg-5和Beclin-1的表达显著上调(P<0.05),自噬蛋白LC3-Ⅱ的组织分布也显著增加(P<0.05)。结果表明,高铜可导致雌性大鼠卵巢发生氧化损伤和自噬,自噬增加可能是氧化损伤诱导的,而过多自噬则加重铜对卵巢的损伤。

To investigate the effects of high level copper on ovaries of female rats,exposure of twenty-four healthy 20-day-old rats to 15,30,60,120 mg/kg copper diets for 6 months and then we analyzed the content of copper in plasma and ovaries,pathological changes of the ovary,the antioxidant indices,expression of autophagy-related genes(LC3-Ⅰ,LC3-Ⅱ,Atg-5 and Beclin-1) and protein localization and expression of LC3-Ⅱ,respectively.In result,copper exposure led to accumulation of copper in ovaries significantly,disorganized ovary morphology,increased redox index(SOD activity,MDA content,T-AOC level,P<0.05),increased expression of autophagy-related genes(LC3-Ⅰ,LC3-Ⅱ,Atg-5,Beclin-1,P<0.05) and increased localized expression of autophagy protein LC3-Ⅱ(P<0.05). The above results suggested that high level copper can led oxidative damage and autophagy on ovaries of female rats. Autophagy enhancement may be induced by oxidative damage,however excessive autophagy accelerates the damage of ovaries by copper.