突发寒潮对糖尿病大鼠卒中前状态脑内兴奋性氨基酸代谢通路的影响

摘要

ABSTRACT:Objective To explore the cerebral expression of N-methyl-D-aspartate receptor 1 (NMDAR1)subunit and excitatory amino acid transporter 2(EAAT2)in diabetic rats with pres-troke status caused by sudden cold temperature(SCD).Methods Eighteen-month-old male SD rats were divided into diabetic group(24 rats)and control group(14 rats).Type 2 diabetes was in-duced by intraperitoneal injection of streptozotocin with high-sugar high-fat diet.Diabetic rats,as well as control rats,were equally divided into SCD group and non-SCD group.The SCD procedure was designed as 3 cycles of 12 h light of 22 ℃ and 12 h dark of 4 ℃ at 60%-90% of relative hu-midity.At the endpoint,brains were removed after decollation,and the expression of NMDAR1 and EAAT2 was detected by immunohistochemistry.Results Blood glucose and serum insulin levels in diabetic group were significantly higher than those in control group(P <0.05).In addi-tion,hyperactivity,decreased food intake and weight loss were observed after SCD treatment(P <0.05).In control rats,the expression of NMDAR1 and EAAT2 in SCD group was higher than that in non-SCD group(P <0.05).In addition,the expression of NMDAR1 and EAAT2 signifi-cantly increased in diabetic rats,especially in SCD-treated rats(P <0.01).Conclusion High lev-els of blood glucose lead to increased expression of NMDAR1 and EAAT2 in rat brain.Exogenous cold stress further increases the cerebral expression of NMDAR1 and EAAT2 and promotes the formation of prestroke status in diabetic rats.%目的：探讨突发寒潮对糖尿病大鼠脑卒中发病前脑组织 N-甲基-天（门）冬氨酸受体 NR1亚基（N-Methyl-D-Aspartate receptor 1，NMDAR1）和兴奋性氨基酸转运体2（excitatory amino acid transporter 2，EAAT2）表达的影响。方法选取18月龄老年雄性 SD 大鼠（糖尿病组24只，对照组14只）。糖尿病组腹腔注射链尿佐菌素联合高糖高脂饮食建立大鼠2型糖尿病模型。将对照组及糖尿病组分别均分为寒潮组和非寒潮组，寒潮组置于人工气候箱中，一次寒潮（22℃×12 h、4℃×12 h）为1 d 循环，相对湿度控制在60％～90％，共3 d。在研究终点将大鼠灌注后断头取脑，并用免疫组织化学方法检测脑组织 NMDAR1和 EAAT2表达水平。结果糖尿病组大鼠血糖及血清胰岛素水平均显著高于对照组（P ＜0．05），寒潮后大鼠普遍出现活动、饮食减少、体质量减轻（P ＜0．05）。对照寒潮组脑神经细胞 NMDAR1和 EAAT2的表达水平增加（P ＜0．05）；糖尿病组大鼠无论是否经寒潮干预，脑神经细胞 NMDAR1和 EAAT2的表达水平均明显增加，尤以糖尿病寒潮组更为显著（P ＜0．05）。结论血糖升高导致大鼠脑内 NMDAR1和 EAAT2的 表 达 增 加。在寒潮的外应激作用下，糖尿病大鼠脑组织 NMDAR1和EAAT2的表达进一步增加，促进卒中易感性的环境形成。