内质网应激在氟暴露致小鼠睾丸损伤中的作用

探讨了内质网应激在亚慢性氟暴露致小鼠睾丸损伤中的作用及分子机制.选用健康初断乳ICR雄性小鼠30只，随机分为对照组（C）、低氟组（LF）和高氟组（HF），分别饮用自来水、5、30 mg·L^-1氟化钠水溶液90 d.亚慢性氟暴露结束后，以睾丸脏器系数、睾丸组织氧化/抗氧化酶和形态结构、精子质量、睾丸细胞凋亡、葡萄糖调节蛋白78（GRP78）、CCAAT/增强子结合蛋白同源蛋白（CHOP）、半胱氨酸天冬氨酸蛋白酶12（CASPASE-12）、半胱氨酸天冬氨酸蛋白酶3（CASPASE-3）为观测点.结果表明，与对照组比，LF组和HF组LDH、SOD、T-AOC活性下降，MDA含量上升，HF组GSH-PX活性下降，差异有统计学意义（p<0.05或p<0.01）；LF组可见细胞层次减少、间隙变大，成熟精子数量减少，HF组细胞溶解、层次紊乱，空泡化严重，少见成熟精子；LF组和HF组小鼠的精子活力降低，HF组小鼠精子数量下降，畸形率上升，差异有统计学意义（p<0.05或p<0.01）；LF组和HF组睾丸细胞凋亡指数上升，差异有统计学意义（p<0.01）；LF组和HF组Grp78、Caspase-12、Caspase-3基因表达水平上升，差异有统计学意义（p<0.05或p<0.01）.结果提示，除氧化应激以外，Caspase-12和Caspase-3基因表达异常可能是氟暴露致小鼠睾丸细胞凋亡异常的分子机制之一.

Role of endoplasmic reticulum stress on testicular injury induced by fluoride exposure in male mice

To expore the role of endoplasmic reticulum stress and its molecular mechanism on testicular injury induced by subchronic fluoride exposure in male mice. 30 newly weaned and clean grade ICR male mice were randomly divided into control group (C group, drink tap water), low fluoride group (LF group, drink 5 mg·L^-1 NaF solution) and high fluoride group (HF group, drink 30 mg·L^-1 NaF solution) respectively, and exposed to fluoride for 90 days. At the end of subchronic fluoride exposure, the organ coefficient of testis, morphology and structure, cell apoptosis of testicular tissues, and sperm quality were observed. The oxidation/antioxidant enzyme activity, glucose-regulated protein78(GRP78), CCAAT/enhancer-binding protein homologous protein(CHOP), cysteinyl aspartate specific proteinase-12 (CASPASE-12), cysteinyl aspartate specific proteinase-3 (CASPASE-3)of testicular cell were detected. Compared with the control group, the LDH, SOD, T-AOC activities in LF and HF groups, and GSH-PX activities in HF group were significantly decreased (p<0.05 or p<0.01); the MDA content in the LF and HF groups was significantly increased (p<0.05 or p<0.01). In LF group, the layers of testicular cells were reduced, the cell gaps became larger and the number of mature sperm decreased. Cells were lysed, layers were disordered or vacuolated, and rare mature sperms were found in HF group. The sperm motilities in LF and the HF groups were decreased, the sperm counts in HF group were decreased and malformation rate of sperms were increased, the difference was statistically significant (p<0.05 or p<0.01). The apoptosis index of testicular cells in LF and HF groups was significantly increased (p<0.01). The expression levels of Grp78, Caspase-12, Caspase-3 in LF and HF groups were increased, and the difference was statistically significant (p<0.05 or p<0.01). The results suggested that, in addition to oxidative stress, endoplasmic reticulum stress mediated abnormal expression of Caspase-12 and Caspase-3 may be the one of the molecular mechanisms of abnormal apoptosis induced by fluoride exposure in testicular cells of mice.