Abstract：
Elevation of the homocysteine concentration in the plasma called hyperhomocysteinemia (hHCY) during pregnancy causes a number of pre- and postnatal developmental disorders. The aim of our study was to analyze the effects of H2S donors -NaHS and N-acetylcysteine (NAC) on blood-brain barrier (BBB) permeability in rats with prenatal hHCY. In rats with mild hHCY BBB permeability assessed by Evans Blue extravasation in brain increased markedly throughout life. Administration of NaHS or NAC during pregnancy attenuated hHCY-associated damage and increased endogenous concentrations of sulfides in brain tissues. Acute application of dl-homocysteine thiolactone induced BBB leakage, which was prevented by the NMDA receptor antagonist MK-801 or H2S donors. Rats with hHCY demonstrated high levels of NO metabolite - nitrites and proinflammatory cytokines (IL-1β, TNF-α, IL-6) in brain. Lactate dehydrogenase (LDH) activity in the serum was higher in rats with hHCY. Mitochondrial complex-I activity was lower in brain of hHCY rats. NaHS treatment during pregnancy restored levels of proinflammatory cytokines, nitrites and activity of the respiratory chain complex in brain as well as the LDH activity in serum. Our data suggest that H2S has neuroprotective effects against prenatal hHCY-associated BBB disturbance providing a potential strategy for the prevention of developmental impairments in newborns.
摘要：
怀孕期间血浆中高半胱氨酸浓度的升高称为高同型半胱氨酸血症（hHCY），会导致许多产前和产后发育障碍。我们研究的目的是分析H2S供体-NaHS和N-乙酰半胱氨酸（NAC）对产前hHCY大鼠血脑屏障（BBB）通透性的影响。在具有轻度hHCY的大鼠中，通过伊文思蓝外渗评估的大脑中BBB通透性在整个生命中都显着增加。在怀孕期间施用NaHS或NAC减轻了hHCY相关的损伤并增加了脑组织中硫化物的内源性浓度。急性应用dl-同型半胱氨酸硫内酯诱导BBB渗漏,NMDA受体拮抗剂MK-801或H2S供体阻止了这种情况。hHCY大鼠表现出高水平的NO代谢物-亚硝酸盐和促炎细胞因子(IL-1β，TNF-α,IL-6）在大脑中。hHCY大鼠血清中乳酸脱氢酶（LDH）活性较高。hHCY大鼠脑内线粒体复合物-I活性较低。妊娠期间NaHS治疗可恢复促炎细胞因子水平，亚硝酸盐和大脑中呼吸链复合物的活性以及血清中LDH的活性。我们的数据表明，H2S对产前hHCY相关的BBB紊乱具有神经保护作用，为预防新生儿发育障碍提供了潜在的策略。
