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

乳铁蛋白（LF）是一种结合铁的糖蛋白，尤其在牛奶中含有。我们已经证明，在成年大鼠中，十二指肠内给药的牛- lf （bLF）从肠道吸收并通过受体介导系统进入血液循环。我们发现肠道吸收的部分bLF通过血脑屏障或血脑脊髓屏障到达大脑。本项目主要研究乳铁蛋白对大鼠分离应激相关行为异常的抑制作用。从出生后第2天至第11天，将新生大鼠分别从家鼠笼和鼠坝中分离。在分离日，将新生大鼠分别分离30 min、1 h、2 h和5 h。分离5 h的大鼠在行为测试（升高+迷宫测试）中观察到特殊的异常。bLF （100 mg/kg）注射液（ip）预处理可抑制上述异常行为。有趣的是，在分离前将bLF应用于大坝大鼠时，bLF的效果最强。bLF的这些作用可通过纳洛酮、阿片受体拮抗剂或L-NAME、一氧化氮合酶阻滞剂预处理而被阻断。bLF还能抑制下丘脑-垂体-肾上腺轴反应。足部休克应激引起的血浆皮质酮升高明显受到bLF的抑制。这些结果表明，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.