Suppressive effect of lactoferrin on behavioral abnormality in the maternally separated rats.

乳铁蛋白(LF)是一种铁结合糖蛋白，尤其是牛奶中含有的铁结合糖蛋白。在成年大鼠十二指肠内给药后，BLF从肠道被吸收，并通过受体介导的系统进入血液循环。我们发现肠道吸收的BLF的一部分通过血脑屏障或血脑脊液屏障到达大脑。本研究旨在探讨乳铁蛋白对与母体分离应激相关的行为异常的抑制作用。新生大鼠在出生后第2天至第11天分别从笼子和水坝中分离出来，在分离当天分别分离30分钟、1小时、2小时和5小时，观察到分离后5小时的行为测试(高架+迷宫实验)的异常。预先给予BLF(100 mg/kg)可抑制上述异常行为。有趣的是，当分离前对模型大鼠施加BLF时，BLF的作用最强。阿片受体拮抗剂纳洛酮或一氧化氮合酶阻断剂L可阻断BLF的上述作用。BLF对下丘脑-垂体-肾上腺轴反应也有抑制作用。BLF能显著抑制电击应激引起的成年大鼠血浆皮质酮水平的升高，提示BLF是应激反应的天然介质之一，通过内源性阿片系统和一氧化氮的产生。

Lactoferrin (LF) is known as an iron-binding glycoprotein, especially contained in milk. We have shown that intra-duodenally administered bovine-LF (bLF) was absorbed from intestine and transported into blood circulation via receptor mediated system in adult rats. We found that a part of the intestinally absorbed bLF was reached to the brain passing through a blood-brain-barrier or a blood-cerebrospinal-barrier. In this project, we focused a suppressive effect of lactoferrin on the behavioral abnormalities related with maternally-separated stresses in rats.Newborn rats were separated individually from home cage and dam from a postnatal day (PND) 2 to PND 11. On the separating day, the newborn rats were separated for 30 min, 1 h, 2 hr and 5 h. Particular abnormalities in behavioral test (elevated plus-maze test) were observed in the 5 h separated rats. Pre-treatment with bLF (100 mg/kg) injection (ip) suppressed these abnormal behaviors. Interestingly, the strongest effect of bLF was recognized when the bLF was applied to the dam rats before the separation. These effects of bLF was blocked by pre-treatment with naloxone, opioid receptor antagonist, or L-NAME, nitric oxide synthase blocker. bLF also suppressed hypothalamus-pituitary-adrenal axis reaction. Plasma corticosterone elevation induced by foot-shock stress was significantly suppressed by bLF in the adult rats.These results suggest that bLF is one of the natural mediators in the stress reaction, via endogenous opioid system and nitric oxide production.