2型糖尿病大鼠早期认知功能改变及海马磷酸化N-甲基-D-天冬氨酸受体2B亚基、Wnt3a和去整合素金属蛋白酶10表达的研究

Early changes of cognitive function in type 2 diabetes rat and expression of p-NR2B,Wnt3a and ADAM10 in hippocampus

目的观察T2DM大鼠早期认知功能改变及海马磷酸化N-甲基-D-天冬氨酸受体2B亚基(p-NR2B)、Wnt3a和去整合素金属蛋白酶10(ADAM10)的表达变化。方法将40只健康雄性SD大鼠采用随机数字表法分为对照组(Con,n=20),糖尿病组(DM,n=20)。Con组以普通饲料喂养8周后单次空腹腹腔注射柠檬酸缓冲液。DM组以高脂高糖喂养8周诱导IR后腹腔小剂量注射STZ 35mg/kg,3d后测血糖,血糖≥16.7mmol/L确诊T2DM。造模成功后10、20d分别通过Y迷宫、八臂迷宫检测认知功能改变,17、21、28d取大鼠海马,Western blot测定海马p-NR2B、Wnt3a和ADAM10的表达。结果与Con组比较,DM组在Y迷宫自发活动次数为(6.9±3.2)次,自主选择率(SA%)为(42.2±29.5)%,差异有统计学意义(P<0.05);DM组在八臂迷宫的1、3、6d测试时间分别为(459.2±143.5)s、(357.3±131.7)s、(274.0±145.1)s,较Con组延长(P<0.05),记忆错误(WME)、参考记忆错误(RME)和总记忆错误(TE)比较,差异无统计学意义(P>0.05)。与Con组比较,DM组各时间点海马中p-NR2B、Wnt3a和ADAM10的表达降低(P<0.05)。结论T2DM大鼠海马中p-NR2B、Wnt3a和ADAM10的表达减少可能参与其早期认知功能的下降。

Objective To investigate the early changes of cognitive function in rats with type 2 diabetes （T2DM） and the expression of FNR2B,Wnt3a and ADAM10. Methods A total of 40 healthy male SD rats were divided into two groups according to the random number method： control group （Con,n =20）,diabetes mellitus group （DM, n=20）. Con group were fed on normal diet for 8 weeks, and then injected intraperitoneally with citrate buffer. DM group were fed on high fat and high glucose diet for 8 weeks to induce insulin resistance （IR） and injected intraperitoneally with streptozotocin （STZ） 35 mg/kg. T2DM were diagnosed when blood glucose level ≥16.7 mmol/L after 3 days. The changes of cognitive function were evaluated via Y maze and eight-arm radial maze in the 10^th day and 20^th days of the established model rats. The expression of hippocampal p-NR2B,Wnt3a and ADAM10 were measured by Western blot on the 17^th day, 21^th day, and 28^th day. Results Locomotor activity counts （6.9 ± 3.2） times in DM group and the percentage of spontaneous alternation （42.2 ± 29.5）% in DM group were significant different between Con and DM group（P〈0.05）. The finishing time in I d, 3 d and 6 d of eight- arm radial maze were significantly higher in DM group（459.2 ± 143.5） s, （357.3 ± 131.7） s, （274.0 ± 145. ls）than in Con group（P〈0.05）. There were no significant differences in WME,RME or TE between the two groups （P〈0.05）. The expression of p-NR2B,Wnt3a and ADAM10 in hippocampus were down- regulated at each day point in DM group than in COn group （P〈 0. 05）. Conclusion The down- regulation of p-NR2B, Wnt3a and ADAM10 in the hippocampus may be involved in the reduced cognitive function in rats with T2DM.