半叶马尾藻岩藻聚糖硫酸酯改善环磷酰胺诱导的小鼠卵巢早衰的作用研究

Effect of fucoidan from Sargassum hemiphyllum on cyclophosphamide-induced premature ovarian failure in mice

目的 探索半叶马尾藻(Sargassum hemiphyllum)岩藻聚糖硫酸酯(Fucoidan, SPF)改善环磷酰胺(cyclophosphamide, CTX)诱导的小鼠卵巢早衰(premature ovarian failure, POF)的作用。方法 将ICR雌性小鼠随机分为3组:空白组(Con)、模型组(CTX)、实验组(CTX+SPF),除Con组注射生理盐水外,其余两组通过连续2 d腹腔注射CTX 70 mg/(kg·d),建立小鼠POF模型。建模结束24 h后,CTX+SPF组小鼠接受SPF 200 mg/(kg·d)灌胃治疗,Con组和CTX组灌等量的生理盐水,每日1次,连续4周。观察小鼠体质量、动情周期、脾脏指数、卵巢指数、超氧化物歧化酶(SOD)活性以及丙二醛(MDA)水平、雌二醇(E_(2))以及促卵泡刺激素(FSH)水平变化,Western blot检测卵巢中LC3蛋白含量。结果 与Con组相比,CTX组小鼠的体质量下降(P<0.01),动情周期发生紊乱,卵巢指数和脾脏指数都发生不同程度的下降(P<0.05),血清中E2的含量降低、FSH的含量升高(P<0.01),卵巢中LC3-Ⅱ/LC3-Ⅰ比值增大(P<0.05),自噬增强。与CTX组相比,CTX+SPF组能够有效改善卵巢早衰,并且SPF可以显著改善由CTX诱导的卵巢组织SOD活性和MDA水平的异常(P<0.05)。结论 SPF能够有效改善CTX诱导的小鼠卵巢早衰,其改善机制可能是与改善性周期紊乱、调节雌激素分泌、改善卵巢氧化应激状态、调节自噬水平作用有关。

Objective To explore the effect of fucoidan(SPF) from Sargassum hemiphyllum on cyclophosphamide(CTX)-induced premature ovarian failure(POF) in mice. Methods Female ICR mice were randomly divided into3 groups, including the control group(Con), the model group(CTX), and experimental group(CTX + SPF). Except for the Con group was injected with normal saline, the other two groups were intraperitoneally injected with CTX(70 mg/(kg·d)) for two days. Twenty-four hours after modeling, the mice in the CTX + SPF group were received SPF(200 mg/(kg·d)) by gavage, and the Con group and the CTX group were given the same amount of normal saline once a day for 1 month. The body weight, estrous cycle, spleen index, ovarian index, superoxide dismutase(SOD) activity, malondialdehyde(MDA), estradiol(E_(2)), and follicle-stimulating hormone(FSH) were measured.Western blot was used to detect the expression of LC3 protein in ovary. Results Compared with the control group,the body weight of mice in CTX group was decreased(P < 0.01), the estrous cycle was disturbed, the ovarian index and spleen index were decreased(P < 0.05), the content of serum E2was decreased, the content of FSH was increased(P < 0.01), the LC3-II/LC3-I ratio in ovary was increased(P < 0.05), and autophagy was increased.Compared with CTX group, SPF treatment effectively improved premature ovarian failure, and the abnormality of SOD activity and MDA level in ovarian tissue. Conclusion SPF can effectively improve the premature ovarian failure induced by CTX in mice. Its mechanism may be to improve the disorder of sexual cycle, regulate estrogen secretion, improve the oxidative stress state of the ovary, and regulate autophagy level.