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首页> 外文期刊>Journal of neuroendocrinology >Prolactin stimulates the vascularisation of the retina in newborn mice under hyperoxia conditions
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Prolactin stimulates the vascularisation of the retina in newborn mice under hyperoxia conditions

机译:催乳素在高氧化条件下刺激新生儿小鼠视网膜的血管异化

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The hormone prolactin (PRL) is emerging as an important regulator of ocular blood vessels. PRL is pro-angiogenic and acquires anti-angiogenic properties after undergoing proteolytic cleavage to the PRL fragment, vasoinhibin. The vascularisation of the rodent retina develops after birth when it rapidly expands until completion at the end of the first postnatal week. Exposure of newborn mice to high oxygen levels lowers the rate of blood vessel growth. In the present study, we investigated whether PRL treatment modifies the vascularisation of the retina in newborn mice exposed to high oxygen or to normoxia and whether the retinal conversion of PRL to vasoinhibin may be altered in the neonate. Newborn mice and their nursing mothers were subjected to 75% oxygen or to normoxia from postnatal day (P) 6 to P8 (group 1) or from P2 to P5 (group 2). PRL (2 μg g-1 , i.p., twice a day) or vehicle was injected from P5 to P8 in group 1 and from P1 to P5 in group 2. PRL treatment reduced the retinal inhibition of blood vessel growth and the increase in vascular regression induced by hyperoxia as revealed by immunofluorescence staining of blood vessels and the expression of angiogenesis and apoptosis markers. The pro-angiogenic effect may involve a reduced conversion of PRL to vasoinhibin. Incubation of PRL with retinal extracts showed reduced activity of the PRL-cleaving protease, cathepsin D, in the neonate vs the adult retina that was further reduced under hyperoxia. PRL and the PRL receptor mRNA were expressed at higher levels in the retina at P8 than in the adult, whereas endogenous PRL was undetectable in the circulation at P8. We conclude that PRL has a pro-angiogenic effect in the neonate retina as a result of its reduced conversion to vasoinhibin and that PRL produced by the retina may help promote physiological vascularisation after birth.
机译:催乳素(PRL)是眼部血管的重要调节因子。PRL是促血管生成的,并且在经过蛋白水解切割到PRL片段血管抑制素后获得抗血管生成特性。啮齿类动物的视网膜血管在出生后迅速扩张,直至出生后第一周结束。新生小鼠暴露在高氧水平下会降低血管生长速度。在本研究中,我们研究了PRL治疗是否会改变暴露于高氧或常氧的新生小鼠视网膜的血管生成,以及新生儿PRL向血管抑制素的视网膜转化是否会改变。新生小鼠及其哺乳期母亲从出生后第6天(P)至第8天(第1组)或从第2天至第5天(第2组)接受75%氧气或常氧。PRL(2μg-1,i.p.,每天两次)或溶媒在第1组从P5注射到P8,在第2组从P1注射到P5。血管免疫荧光染色、血管生成和凋亡标记物的表达显示,PRL治疗降低了视网膜对血管生长的抑制以及高氧诱导的血管退化的增加。促血管生成作用可能涉及PRL转化为血管抑制素的减少。PRL与视网膜提取物的孵育显示,与成人视网膜相比,新生儿视网膜中PRL裂解蛋白酶组织蛋白酶D的活性降低,在高氧条件下进一步降低。在P8时,PRL和PRL受体mRNA在视网膜中的表达水平高于成人,而在P8时,内源性PRL在循环中检测不到。我们的结论是,PRL在新生儿视网膜中具有促血管生成作用,因为其转化为血管抑制素的减少,并且视网膜产生的PRL可能有助于促进出生后的生理血管生成。

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