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目的研究糖尿病大鼠不同血糖水平下脑内胶质细胞源性神经营养因子(GDNF)表达的变化。方法将30只Wistar大鼠随机均分为糖尿病血糖未控制(DM1)组、糖尿病血糖控制(DM2)组和对照(NC)组。12周后检测血糖与糖化血红蛋白(HbA1c)水平,免疫组织化学(SP)法检测GDNF蛋白表达,HE染色观察海马及大脑皮层神经元细胞计数和形态学变化。结果海马CA区和大脑皮层的GDNF蛋白表达均按NC组>DM2组>DM1组依次减弱(P<0.05),且均与HbA1c水平之间呈负相关(r分别为-0.961和-0.963,P<0.05)。与NC组相比,DM1组和DM2组海马CA区神经元无明显减少,而海马及大脑皮层神经元呈明显退形性形态学改变。结论长期慢性高血糖可下调海马和大脑皮层GDNF蛋白表达,从而可能引起中枢神经病变。
Objective To study the changes of glial cell line-derived neurotrophic factor (GDNF) expression in diabetic rats with different blood glucose levels. Methods Thirty Wistar rats were randomly divided into diabetes control group (DM1), diabetes control group (DM2) and control group (NC). The levels of blood glucose and HbA1c were measured 12 weeks later. The expression of GDNF protein was detected by immunohistochemistry (SP). The neuronal cell counts and morphological changes of hippocampus and cerebral cortex were observed by HE staining. Results The expression of GDNF protein in hippocampal CA area and cerebral cortex were decreased in order of NC group> DM2 group> DM1 group (P <0.05), and negatively correlated with HbA1c level (r = -0.961 and -0.963, P <0.05). Compared with NC group, neurons in hippocampal CA area of DM1 group and DM2 group were not significantly reduced, while neurons of hippocampus and cerebral cortex showed obvious degenerative morphological changes. Conclusion Long-term chronic hyperglycemia can down-regulate GDNF protein expression in the hippocampus and cerebral cortex, which may cause central nervous system diseases.