7,8-二羟基黄酮纳米粒子通过保护卵巢储备缓解代谢综合征

7,8-Dihydroxyflavone nanoparticles alleviate metabolic syndrome by protecting ovarian reserve

摘要:

以芜菁多糖为壁材构建了7,8-二羟基黄酮（7,8-DHF）的纳米粒子，并对两种不同膳食模式（高脂和低脂）饲养的C57BL/6J雌性小鼠进行为期24周的干预，以探究7,8-DHF纳米粒子对小鼠代谢综合征（MetS）的改善作用和机制。所用7,8-DHF及其纳米粒子的剂量均为10 mg/kg·体重（BW）（以7,8-DHF的相对质量分数为标准）。干预结束后，采用分子生物学方法对MetS各项指标、炎症因子及卵巢储备功能进行了测定。结果表明，7,8-DHF及其纳米粒子均可有效缓解小鼠MetS的症状：显著（P < 0.05）降低高脂膳食（HFD）诱导的小鼠体重过度增长，相比于高脂对照组，7,8-DHF及7,8-DHF纳米粒子组体重分别下降了8.5%和16.4%；显著（P < 0.05）改善血脂、血糖及血胰岛水平；显著（P < 0.05）改善小鼠的葡萄糖耐受性和胰岛素敏感性；并且，发现由芜菁多糖构建的7,8-DHF纳米粒子对MetS各项指标的干预效果相较于单独的7,8-DHF更加显著。更进一步发现，7,8-DHF及其纳米粒子能够显著降低（P < 0.05）血清中循环脂多糖（LPS）、肿瘤坏死因子alpha（TNF-α）和白介素-6（IL-6）等炎症相关指标；并且，7,8-DHF及其纳米粒子干预可以有效保护小鼠卵巢储备功能，维持其正常的动情周期和血清雌二醇（E2）、卵泡雌激素（FSH）的水平稳态。推测7,8-DHF及其纳米粒子对雌鼠MetS的干预作用，可能是通过缓解肠道菌群介导的全身炎症并作用于对卵巢储备功能的保护而实现的。

Abstract:

To investigate the preventive effect and related machanism of 7,8-dihydroxyflavone (7,8-DHF) nanoparticles on metabolic syndrome (MetS), C57BL/6J female mice fed with two different dietary patterns (high-fat and low-fat) were intervened with 7,8-DHF nanoparticles (constructed using turnips polysaccharide as wall material) for 24 weeks. The dose of 7,8-DHF and its nanoparticles were all 10 mg/kg· body weight (BW) (based on the relative mass fraction of 7,8-DHF). At the end of the intervention, related MetS indexes, inflammatory factors and ovarian reserve function were determined by molecular biology techniques. It was shown that both 7,8-DHF and its nanoparticles could alleviate symptoms of MetS: significantly (P < 0.05) down-regulated the excessive body weight gain induced by high-fat diet (HFD) in mice, compared with the HFD control group, the body weights of mice in 7,8-DHF and 7,8-DHF nanoparticle groups decreased by 8.5% and 16.4%, respectively; obviously (P < 0.05) improved blood lipid, fasting blood glucose and insulin levels; markedly improved glucose tolerance and insulin sensitivity of mice; In addition, the 7,8-DHF nanoparticles constructed with turnips polysaccharide exhibited a better anti-MetS effect compared with 7,8-DHF alone. Furthermore, it was found that 7,8-DHF and its nanoparticles could significantly reduce the levels of circulating lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in serum. Moreover, 7,8-DHF and its nanoparticles can effectively protect the ovarian reserve function of mice, maintain the normal estrus cycle and the homeostasis of serum estradiol (E2) and follicular estrogen (FSH). Thus, it is speculated that the intervention effect of 7,8-DHF and its nanoparticles on MetS in female mice might attributed to its Protective effect on the ovarian reserve function by alleviating the systemic inflammation mediated by gut microbiota.