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目的:探讨持续高血糖对大鼠海马颗粒下区(subgranular zone,SGZ)神经干细胞状态的影响及可能机制。方法:SD大鼠注射链脲佐菌素(streptozotocin,STZ)诱导1型糖尿病模型,腹腔注射5-溴脱氧尿嘧啶核苷(bromodeoxyuridine,Brd U)标记新生细胞。利用免疫组化法检测海马SGZ区Ki67,5-溴脱氧尿嘧啶核/双皮质素(bromodeoxyuridine/doublecortin,Brd U/DCX)标记的阳性细胞。利用免疫印迹法检测海马胰岛素受体β(insulin receptorβ,IRβ),糖元合成酶激酶3β(pho-glycogen synthase kinase-3β,GSK3β),β-链蛋白(β-Catenin)表达水平。结果:STZ注射大鼠胰岛素降低,血糖升高;糖尿病大鼠海马区Ki67阳性细胞,Brd U/DCX阳性细胞和对照组比较明显减少,海马区IRβ,pho-GSK3β,β-Catenin表达水平和对照组比较显著下降(P<0.05)。结论:STZ诱导的1型糖尿病大鼠海马SGZ区新生细胞增值能力下降,细胞分化异常,这一变化和海马区胰岛素信号下调,GSK3β活化,β-Catenin降解增加有关。
Objective: To investigate the effect of hyperglycemia on the status of neural stem cells in subgranular zone (SGZ) of rat hippocampus and its possible mechanism. Methods: SD rats were injected with streptozotocin (STZ) to induce type 1 diabetes mellitus and neonatal cells were labeled with bromodeoxyuridine (BrdU). Immunohistochemistry was used to detect Ki67, BrdU / DCX labeled positive cells in SGZ hippocampus. Western blotting was used to detect the expression of insulin receptorβ (IRβ), glycogen synthase kinase-3β (GSK3β) and β-catenin in hippocampus. Results: Compared with control group, the expression of Ki-67 positive cells, BrdU / DCX positive cells in hippocampus of diabetic rats and the control group were significantly decreased and the levels of IRβ, pho-GSK3β and β-Catenin in hippocampus were significantly decreased Group decreased significantly (P <0.05). CONCLUSION: The ability of proliferation of dendritic cells in STZ-induced type 1 diabetes mellitus in SGZ is down-regulated and cell differentiation is abnormal. This change is related to the down-regulation of insulin signal and the activation of GSK3β and the increase of β-Catenin in hippocampus.