Cui Xiangrong, Long Chunlan, Zhu Jing, Tian Jie
Cell Physiol Biochem. 2017;41(2):598-608. doi: 10.1159/000457881. Epub 2017 Feb 3.
Statins can reduce reproductive damage induced by obesity or high-fat diet (HFD), but the specific regulatory mechanisms are largely unknown. Since mTOR/p70s6k sinaling promotes spermatogonia proliferation and spermatogenesis, we hypothesized that this pathway will be involved in the protective effects of statin in HFD-induced reproductive dysfunction.
Male Sprague Dawley rats (3 weeks old) were randomly divided into a control group (standard diet), HFD group, and a fluvastatin group (HFD + fluvastatin at 6mg/kg, once daily by oral gavage). After 8 weeks, body weight was obtain and rats were sacrificed. Weights of the testes, gross morphology, sperm parameters, circulating levels of sex hormones, lipid levels, and tissue mTOR, p-P70s6k were measured. Another set of male rats were treated with rapamycin or vehicle. Flow cytometry was used to detect the spermatogonia marker c-kit and cell cycle. p-P70s6k expression was analyzed by Western blot.
HFD not only results in rat obesity but also leads to spermatogenetic damage and fluvastatin was able to partially block the effects of HFD. Fluvastatin also partially reversed the suppression of mTOR and p-p70s6k expresson.
Our data suggest that fluvastatin has protective effects on reproductive function in obese male rats most probably through enhanced signaling of mTOR.
他汀类药物可减轻肥胖或高脂饮食（HFD）所致的生殖损伤，但其具体调控机制尚不清楚。由于mTOR/p70s6k信号通路可促进精原细胞增殖和精子发生，我们推测该通路参与了他汀类药物对HFD诱导的生殖功能障碍的保护作用。
将3周龄雄性Sprague Dawley大鼠随机分为对照组（标准饮食）、HFD组和氟伐他汀组（HFD+6mg/kg氟伐他汀，每日经口灌胃1次）。8周后，测量体重并处死大鼠。检测睾丸重量、大体形态、精子参数、性激素循环水平、血脂水平以及组织中的mTOR、p-P70s6k。另一组雄性大鼠用雷帕霉素或溶剂处理。采用流式细胞术检测精原细胞标志物c-kit和细胞周期。通过蛋白质免疫印迹法分析p-P70s6k的表达。
HFD不仅导致大鼠肥胖，还导致生精损伤，氟伐他汀能够部分阻断HFD的影响。氟伐他汀还部分逆转了mTOR和p-p70s6k表达的抑制。
我们的数据表明，氟伐他汀对肥胖雄性大鼠的生殖功能具有保护作用，最可能是通过增强mTOR信号通路实现的。
