血糖波动对2型糖尿病大鼠认知功能及海马Bax/Bcl-2的影响

摘要

[目的]探讨血糖波动对糖尿病大鼠认知功能和海马Bax/Bcl-2的影响.[方法]取45只雄性大鼠禁食不禁水16h,用链脲佐菌素30 mg·kg-1加高脂饲料诱导2型糖尿病大鼠模型,挑选出糖尿病大鼠30只,分成糖尿病模型组(Diabetes Model,M)、持续高血糖糖尿病组(High Glucose Diabetes Sustain Model,MS)、血糖波动糖尿病组(Glucose Fluctuate Diabetes Model,MF),另取10只正常大鼠做正常对照组(Normal,N).血糖波动糖尿病组错时腹腔注射葡萄糖0.38 g·kg-1和皮下注射胰岛素1U制备糖尿病血糖波动模型.血糖波动6周后,进行水迷宫定位航行实验和空间探索实验,同时检测海马组织中Bax、Bcl-2的表达.[结果]M组、MS组、MF组比N组逃避潜伏期明显增长(P＜0.05),空间探索实验结果显示60s内穿越平台所在位置的次数明显下降,在平台所在象限内的游泳距离明显减少(P＜0.05).MF组和M组、MS组相比.逃避潜伏期进一步增长(P＜0.05),空间探索实验结果显示60s内穿越平台所在位置次数也明显下降,在平台所在象限游泳距离也减少(P＜0.05).MF组、M纽、MS组Bcl-2的表达较N组显著下降,Bax显著升高(P＜0.05).MF组Bcl-2的表达较M组、MS组进一步下降,Bax进一步升高(P＜0 05).[结论]血糖波动能加重损伤糖尿病大鼠的学习记忆功能,并促进海马组织的凋亡相关蛋白Bax/Bcl-2的表达,诱导海马神经元的凋亡.%[Objective] To explore the effection of glucose fluctuation on the cognitive function and the Bax/Bcl-2 in hippocampal of rats with type 2 diabetes mellitus. [Methods] The SD rats were randomly divided into four groups: normal group(N); diabetes model group(M);high glucose sustain diabetes model group(MS); glucose fluctuate diabetes model group(MF). The diabetic rats model was developed by injection with streptozotocin(STZ) 30 mg·kg-1, regularly staggered insulin 1U and glucose 0.38 mg·kg-1 administration was used to set up blood glucose fluctuation model. After six weeks of establishing MF, Morris Water maze was used to perform training trial and probe trial in order to detect spatial learning and memorl abilities.After Morris Water maze experiment, detect the content of Bax and Bcl-2 in hippocampal tissue of rats. [Results] The escape latency of M MS MF was all significantly higher than that of N, compared to the N, the swimming distance and the number of rats passing hidden platform in the quadrant of hidden platform in 60s significandy decreased. Compared to MS and M, the escape latency was significantly increased, the swimming distance in the quadrant of hidden platform and the number of rats passing hidden platform in the quadrant of hidden platform in 60s were further significantly decreased. Compared to N, the expression of Bax in M MS MF all significandy increased while the expression of Bel-2 significantly decreased. Compared to M and MS, the expression of Bax in MF further significandy increased while the expression of Bcl-2 significandy decreased. [Conclusion] Glucose fluctuation can influence the apoptosis of protein Bax/ Bcl-2 in order to induce hippocampal neuron apoptosis, which aggravates damage learning and memory abilities of rats with type 2 diabetes.