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目的 检测糖尿病小鼠脑内Tau蛋白不同位点的磷酸化状态及 β淀粉样肽表达的改变 ,进一步探讨糖尿病脑病的机理并观察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肽进行保护。 4周后 ,取小鼠脑组织做BT 2、Rllle免疫组织化学染色。另一部分小鼠断头取脑 ,分离海马 ,做Tau 1、AT 8、Aβ1 16和管蛋白 (tubulin)抗体蛋白免疫印迹。 结果 糖尿病小鼠脑海马神经元内正常Tau蛋白含量减少 ,Tau蛋白 192 2 0 2位点及 194 198位点过度磷酸化 ,而Thr2 31和Thr181位点未被磷酸化 ;管蛋白的表达明显减少 ,而APP的表达则增多。用APP17肽对糖尿病小鼠进行保护后 ,Tau蛋白的磷酸化程度降低 ,APP和Tubulin的表达恢复到接近正常水平。 结论 糖尿病小鼠脑内Tau蛋白过度磷酸化、tubulin表达减少 ,微管结构受损 ,同时APP表达增加造成Aβ含量增多 ,引起神经元损害。对糖尿病小鼠应用APP17肽使Tau保持磷酸化程度、APP及tubulin表达接近正常 ,因此 ,APP17肽在防止神经元变性方面有重要意义
Objective To investigate the phosphorylation of different sites of Tau protein in brain of diabetic mice and the change of amyloid beta peptide expression, to further explore the mechanism of diabetic encephalopathy and to observe the effect of APP17 peptide. Methods Diabetic mice were induced with streptozotocin and APP17 peptide was injected subcutaneously for protection. After 4 weeks, the brain tissue of mice was taken for BT 2 and Rllle immunohistochemical staining. The other part of the mice was decapitated and the hippocampus was separated to immunoblot immunoblot with antibodies to Tau 1, AT 8, Aβ1 16 and tubulin. Results The content of normal Tau protein was decreased in diabetic hippocampal neurons. Tau protein 192 202 and 194 198 sites were over-phosphorylated while the Thr2 31 and Thr181 sites were not phosphorylated and the expression of tubulin was significantly decreased , While the expression of APP increased. Protection of diabetic mice with the APP17 peptide reduced the phosphorylation of Tau protein and the expression of APP and Tubulin returned to near-normal levels. Conclusions Tau hyperphosphorylation, tubulin expression and microtubule structure are impaired in diabetic mice brain. At the same time, the increase of APP expression leads to the increase of Aβ content and neuronal damage. Application of APP17 peptide to diabetic mice maintains Tau phosphorylation and APP and tubulin expression are near normal, therefore, APP17 peptide is of great importance in preventing neuronal degeneration