血糖波动对2型糖尿病大鼠认知功能及N-甲基-D-天（门）冬氨酸受体表达的影响

Effect of blood glucose fluctuation on cognitive function and expression of N-methyl-D-aspartate receptor in type 2 diabetic rats

目的探讨血糖波动对2型糖尿病大鼠认知功能及N-甲基-D-天(门)冬氨酸(NMDA)受体表达的影响。方法33只清洁级雄性SD大鼠,适应性喂养1周后,随机取11只作为正常对照组,其余大鼠用于建立2型糖尿病模型。采用小剂量链脲佐菌素45 mg/kg腹腔注射建立2型糖尿病模型,非同日两次测得的随机血糖>16.7 mmol/L为造模成功。将模型大鼠随机分为持续高血糖组(n=11)和血糖波动组(n=11),2型糖尿病模型成功后,血糖波动组大鼠皮下注射普通胰岛素2次/d,诱导血糖波动大鼠模型。比较三组大鼠的潜伏期、潜伏期距离、穿越平台次数及12周后大鼠海马组织中NMDA受体NR2B亚基mRNA表达。结果血糖波动组大鼠的潜伏期长于正常对照组和持续高血糖组,持续高血糖组大鼠的潜伏期长于正常对照组,差异均有统计学意义(P<0.05);血糖波动组大鼠的潜伏期距离长于正常对照组和持续高血糖组,持续高血糖组大鼠的潜伏期距离长于正常对照组,差异均有统计学意义(P<0.05);血糖波动组大鼠穿越平台次数少于正常对照组和持续高血糖组,持续高血糖组大鼠穿越平台次数少于正常对照组,差异均有统计学意义(P<0.05);血糖波动组大鼠海马组织中的NMDA受体NR2B亚基mRNA表达水平低于正常对照组和持续高血糖组,持续高血糖组大鼠海马组织中的NMDA受体NR2B亚基mRNA表达水平低于正常对照组,差异均有统计学意义(P<0.05)。结论血糖波动比持续高血糖更能加重大鼠认知功能的损害。糖尿病大鼠海马组织NMDA受体NR2B亚基mRNA表达量降低,且血糖波动同持续高血糖相比,NR2B亚基mRNA表达量降低更加明显。

Objective To investigate the effect of blood glucose fluctuation on cognitive function and N-methyl-D-aspartate(NMDA)receptor expression in type 2 diabetic rats.Methods Thirty-three male clean Sprague-Dawley rats were randomly selected 11 ones for normal control group after one week of adaptive feeding.The rest were used to establish the type 2 diabetic rats model.A model of type 2 diabetes mellitus was established by intraperitoneal injection of a low-dose streptozotocin(45 mg/kg).The standard of successful modeling was the value of glucose>16.7 mmol/L measured randomly twice a day.After that,rats were randomly divided into persistent hyperglycemia group(n=11)and glucose fluctuation group(n=11).After successful type 2 diabetes model,rats in the blood glucose fluctuation group were subcutaneously injected with insulin twice a day to induce the blood glucose fluctuation rat model.The latency,latency distance,number of plateau crossings and the expression of NMDA receptor NR2B subunit in hippocampus of rats after 12 weeks were compared among the three groups.Results The latent period of the rats in the glucose fluctuation group was longer than that in the normal control group and the persistent hyperglycemia group,the latency of the rats in the persistent hyperglycemia group was longer than that in the normal control group,the differences were statistically significant(P<0.05).The latency of the blood glucose fluctuation group was longer than that of the normal control group and the persistent hyperglycemia group,the latency of the rats in the persistent hyperglycemic group was longer than that in the normal control group,the differences were statistically significant(P<0.05).The number of crossing platform in the blood glucose fluctuation group was fewer than that in the normal control group and the persistent hyperglycemia group,the number of crossing platform in the persistent hyperglycemic group was fewer than that in the normal control group,the differences were statistically significant(P<0.05).The expression level of NMDA receptor NR2B subunit mRNA in hippocampal tissues of the glucose fluctuation group was lower than that of the normal control group and the persistent hyperglycemia group,the expression level of NMDA receptor NR2B subunit mRNA in the hippocampus of the persistent hyperglycemic group was lower than that of the normal control group,the differences were statistically significant(P<0.05).Conclusion Glucose fluctuation can aggravate cognitive impairment in rats more than persistent hyperglycemia.The expression of NMDA receptor NR2B subunit in hippocampus of diabetic rats is decreased,and the expression of NR2B subunit is decreased more significantly than that of persistent hyperglycemia.