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目的:研究渥曼青霉素能否在体诱导tau蛋白阿尔采末样磷酸化以及褪黑激素的对这种效应的拮抗作用.方法:采用立体定位技术向大鼠侧脑室注射渥曼青霉素和褪黑激素,免疫组织化学和免疫印迹技术观察磷酸化tau蛋白的分布及含量,电子显微镜观察轴突结构.结果:注射渥曼青霉素(10μmol·L~(-1))6h后,海马CAI锥体神经元tau蛋白的Ser-396/404位点被磷酸化,神经元轴突膨胀,部分髓鞘脱落.免疫印迹结果表明,渥曼青霉素注射后1h到6h,tau蛋白的Ser-396/404位点磷酸化逐渐增加,6h到24h逐渐减少,6h为tau蛋白的Ser-396/404磷酸化的峰值.提前12h注射褪黑激素(10μmol·L~(-1)和100μmol·L~(-1)),可部分对抗渥曼青霉素(10μmol·L~(-1))注射6h后诱导的tau蛋白Ser-396/404磷酸化.结论:在体注射渥曼青霉素可诱导大脑tau蛋白阿采末样磷酸化,褪黑激素可部分拮抗这一损伤效应.
OBJECTIVE: To study whether wortmannin can induce the Alzheimer-like phosphorylation of tau protein and the antagonism of melatonin to this effect in vivo.Methods: Stereotaxic injection of wortmannin and melatonin Hormone, immunohistochemistry and Western blotting were used to observe the distribution and content of phosphorylated tau protein.Electron microscopy was used to observe axonal structure.Results: After 6 h injection of wortmannin (10 μmol·L -1), hippocampal CAI pyramidal neurons The Ser-396/404 site of tau was phosphorylated, the axons of the neurons expanded and some of the myelin exfoliated. Western blotting showed that Ser-396/404 site of tau protein was detected at 1 h to 6 h after wortmannin injection Phosphorylation gradually increased from 6 h to 24 h and decreased gradually, and 6 h was the peak of phosphorylation of Ser-396/404 of tau protein.After 12 h injection of melatonin (10 μmol·L -1 and 100 μmol·L -1) ) Partially antagonized the phosphorylation of tau protein Ser-396/404 induced by wortmannin (10 μmol·L -1) for 6 h.Conclusion: Injection of wortmannin can induce brain tau protein Phosphorylation of melatonin partially antagonizes this damaging effect.