Arc/Arg3.1在糖尿病性脑病大鼠海马组织中的表达及其与认知功能改变的关系

Expression of Arc/Arg3.1 in diabetic rat hippocampus and its relationship with cognitive function

目的：探讨糖尿病大鼠认知功能与海马Arc蛋白和β淀粉样蛋白（Aβ）表达的相关性，探讨突触可塑性在糖尿病性脑病（DE）发病机制中的作用。方法30只SPF级雄性8周龄大鼠随机分为对照组和糖尿病组，糖尿病组高脂饮食喂养4周后腹腔注射链脲佐菌素建立2型糖尿病大鼠模型，观察不同阶段动物的体质量、空腹血糖（FBG）、空腹血清胰岛素（FSI），并计算胰岛素敏感指数（ISI）。实验末行水迷宫测试评估两组大鼠认知功能；酶联免疫吸附测定法、免疫组织化学法和蛋白质印迹法检测大鼠海马组织Aβ和Arc的表达。结果糖尿病组大鼠在目标象限的探索时间较对照组缩短（P＜0.01），原平台穿越次数较对照组减少（P＜0.01）。糖尿病组Aβ表达较对照组升高（P＜0.01），Arc/Arg3.1表达降低（P＜0.01）。结论糖尿病大鼠认知功能受损可能与Arc表达降低导致突触可塑性失衡加剧Aβ的沉积和神经元损伤有关。

Objective To analyze the correlation of cognitive function with the expression of Arc protein and amyloid-beta peptide （Aβ） in the hippocampus of diabetic rats, and to assess the role of synaptic plasticity in the possible pathogenesis of diabetic encephalopathy （DE）. Methods Thirty male SPF SD rats （8 weeks old） were randomly assigned to diabetes mellitus （DM） group and control group. After 4 weeks of high fat diet feeding, the rats of DM group were injected intraperitoneally with streptozotocin at a dose of 30mg/kg to establish diabetic model. Body mass, fasting blood glucose （FBG）, and fasting serum insulin （FSI） were monitored at several stages, and insulin sensitivity index （ISI） was calculated. At the end of the experiment, water maze test was carried out to evaluate the cognition of all the rats. The expression of Arc and Aβin the hippocampus was detected and observed by ELISA, immunohistochemistry and Western blotting. Results The DM group spent shorter time in the target quadrant （P〈0.01） and lower frequency of crossing the original platform site （P〈0.01） than the control group. The expression level of Aβwas obviously higher, while that of Arc/Arg3.1 significantly lower in the DM group than in the control group （P〈0.01）. Conclusion The cognitive impairment in diabetic rats is possibly related to the decreased Arc expression-induced synaptic plasticity imbalances, and further increased Aβdeposition and neuronal damage.