摘要
目的研究糖尿病小鼠脑内Ｔａｕ蛋白是否过度磷酸化并观察ＡＰＰ１７肽的作用。方法用链脲佐菌素诱发小鼠糖尿病模型，并皮下注射ＡＰＰ１７肽对糖尿病小鼠进行保护。４周后，取脑组织做ＡＴ８、Ｔａｕ１、ＰＰ２Ｂ及用ＰＰ２Ｂ脱磷酸后的Ｔａｕ１免疫组化染色。结果糖尿病小鼠脑内ＡＴ８阳性反应神经元数目多，胞浆和突起深染，而正常小鼠及ＡＰＰ１７肽保护的糖尿病小鼠脑内阳性反应神经元数目少，染色淡；糖尿病小鼠海马内ＰＰ２Ｂ阳性反应神经元数目比正常小鼠明显减少，用ＡＰＰ１７肽保护后染色结果与正常小鼠接近。结论糖尿病小鼠脑内出现Ｔａｕ蛋白的过度磷酸化，即在丝氨酸２０２／苏氨酸２０５位点被磷酸化，ＰＰ２Ｂ表达减少可能是导致Ｔａｕ蛋白过度磷酸化的主要原因。用ＡＰＰ１７肽可使ＰＰ２Ｂ表达正常而保护Ｔａｕ蛋白不被过度磷酸化。
Objective To study whether Tau protein is hyperphosphorylated in brain tissues of diabetic mice and to study the effect of APP 17 peptide. Methods Mouse diabetic model was produced with streptozotocin, and APP 17 peptide as a protective was injected subcutaneously into diabetic mice. Four weeks later fixative was injected intravascularly into the mice, brain was removed and cryostat sections prepared. Immunohistochemical staining was done with AT 8, Tau 1, PP 2B antibodies, and again with Tau 1 antibody after dephosphorylation. Results In the brains of diabetic mice positive AT 8 reacting neurons were numerous, the cytoplasm was darkly stained, and 2 3 level dendritic processes were visible, while in normal mice and in APP 17 peptide protected diabetic mice positive cells were scarce and were poorly stained. PP 2B enzyme was markedly diminished in the brains of diabetic mice in comparison to the controls. After APP 17 peptide protection positive staining of PP 2B approximated that in the controls. Conclusion Tau protein is hyperphosphorylated at Ser 202/Thr 205 sites in the brains of diabetic mice, which may be, chiefly due to reduction in PP 2B content. The use of APP 17 peptide can normalize the expression of PP 2B and protect Tau protein from hyperphosphorylation.
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
1999年第1期38-40,共3页
Chinese Journal of Endocrinology and Metabolism
关键词
糖尿病
TAU蛋白
超磷酸化
小鼠
痴呆
Diabetic encephalopathy Tau protein Hyperphosphorylation Mice
