溴氰菊酯对大鼠卵巢甾体激素合成的影响

Effects of deltamethrin on ovarian steroidogenesis in rats

目的探讨溴氰菊酯(Deltamethrin,DLT)对大鼠卵巢甾体激素合成的影响及相关的分子机制。方法不同剂量DLT暴露处理大鼠和原代颗粒细胞;取DLT暴露后的大鼠血清和培养上清液,电化学发光法测定雌二醇和孕酮的水平;Western Blot法检测DLT暴露后大鼠卵巢组织及原代培养颗粒细胞中甾体激素合成关键酶:甾体激素合成急性调节蛋白(StAR)、胆固醇侧链裂解酶(P450scc)、芳香化酶的表达量,同时检测组蛋白去乙酰化酶Sirt1的蛋白表达。结果体、内外实验中,DLT各处理组大鼠血清、原代颗粒细胞培养上清液中雌二醇水平均显著升高(体内实验P<0.05,体外实验P<0.001);体内实验中DLT各处理组大鼠血清孕酮水平均显著降低(P<0.05),而体外实验中DLT各处理组原代颗粒细胞培养上清液孕酮水平无显著变化(P>0.05);体、内外实验中DLT各处理组大鼠卵巢组织、原代培养颗粒细胞中StAR、P450scc、芳香化酶以及Sirt1的表达量均显著升高(P<0.01)。结论 DLT能影响大鼠卵巢雌二醇和孕酮的合成,其机制可能与其关键酶表达的变化有关。

Objective:To explore the effects and related molecular mechanisms of deltamethrin(DLT)on ovarian steroidogenesis in rats.Methods:Sprague-Dawley rats and primary cultures of rat granulosa cells were treated with different doses of DLT.The levels of estradiol and progesterone in DLT-treated rat serum or granulosa cell culture supernatant were determined by electrochemiluminescence immunoassay.The expression of key enzymes related with steroid hormone synthesis:steroidogenic acute regulatory protein(StAR),cytochrome P450scc enzyme(P450scc)and aromatase,as well as the expression of sirtuin 1(Sirt1)in DLT-treated rat ovary tissues or cultured rat granulosa cells were detected by Western Blot.Results:Both in vivo and in vitro experiments showed that the estradiol levels in rat serum or primary granulocyte culture supernatants were significantly increased in each DLT treatment group(P<0.05 in vivo,P<0.001 in vitro).DLT treatment decreased the progesterone level in vivo(P<0.05),but did not significantly change the level of progesterone in vitro(P>0.05).Both in vivo and in vitro experiments showed that the expression of StAR,P450scc,aromatase and Sirt1 in DLT-treated rat ovary tissues or cultured rat granulosa cells were all significantly increased(P<0.01).Conclusions:DLT can affect estradiol and progesterone production of rat ovary,and the mechanism may be associated with the change of gene expression of key enzymes.