苦马豆素抑制N-聚糖加工对生殖激素分泌功能的影响

苦马豆素（SW）中毒可引起生殖激素分泌紊乱，其中，促性腺激素是糖蛋白，由N-聚糖糖基化修饰调控其活性和功能。SW是N-聚糖加工过程中ɑ-甘露糖苷酶的抑制剂，而SW如何通过改变N-聚糖加工过程进一步影响生殖激素的分泌功能尚不明确。因此，本试验建立SW染毒妊娠期小鼠模型，利用MALDI-TOF-MS质谱法检测糖蛋白N-聚糖糖链结构的变化，分析N-聚糖加工过程中糖基酶的活性和生殖激素水平及其受体蛋白表达量。随着SW染毒时间的延长，染毒组小鼠垂体前叶糖蛋白的5种复合型N-聚糖糖链结构消失，而新增加3种杂合型N-聚糖糖链结构；N-聚糖糖基转移酶和糖苷酶的活性均显著下降；进一步发现染毒组小鼠卵巢促性腺激素受体、雌二醇和孕酮受体蛋白表达量显著低于对照组，并且生殖激素分泌水平也出现显著下降。SW可显著抑制N-聚糖糖基酶的活性使糖蛋白上N-聚糖糖链结构发生改变，影响促性腺激素及其受体的活性，使其对下游类固醇激素分泌的调控作用失衡，最终导致小鼠妊娠期生殖激素分泌紊乱。

Swainsonine Affects the Secretion of Reproductive Hormones by Inhibiting N-glycan Processing

Swainsonine (SW) can cause disorders of reproductive hormones. Gonadotropins are glycoprotein hormones, so they are regulated by N-glycosylation modifications. ɑ-mannosidase, a key enzyme that accelerates the processing of N-glycosylation modifications, can be inhibited by SW. So how does SW affect the structure of N-glycan and the secretion performance of reproductive hormone is unclear. Thus, this test was conducted by intraperitoneal injection of SW exposed mice to establish models of poisoning. The changes of N-glycan structure in their pituitary tissues were detected by MALDI-TOF-MS mass spectrometry; the activity of glycosylase, the level of reproductive hormone, the quantity of reproductive hormone receptors were analyzed. With the extension of injection time, the five composite glycosides of the pituitary glycoprotein in the poisoned group disappeared, and three hybrid glycosides were added. The activities of glycosyltransferase and glycosidase in the poisoned group were significantly decreased. There were further found that the expression levels of gonadotropin receptor, estradiol and progesterone receptor proteins in the poisoned group were significantly lower than those in the control group, and the secretion levels of reproductive hormones were also significantly decreased. SW can significantly inhibit the activity of N-glycan glycosylase and cause changes of normal N-glycan structure; it has a negative influence on the activities of gonadotropins and their receptors, causing the regulation of downstream steroid hormone secretion out of balance, and eventually, reproductive hormone regulation can be disrupted.