丁苯酞对糖尿病小鼠学习记忆功能和海马炎症反应的影响

Effects of Dl-3-n-butyphthalide on learning and memory function and hippocampal inflammatory response in diabetic mice

目的研究丁苯酞对糖尿病db/db小鼠学习记忆功能的和海马区炎症反应的作用及其机制。方法db/db小鼠是瘦素受体缺陷型自发肥胖2型糖尿病小鼠。按照随机数表法将db/db小鼠分为2组:模型组、实验组,每组8只;同窝血糖正常的杂合子db/m小鼠作为正常组(8只)。实验组给与120 mg·kg^-1·d^-1丁苯酞灌胃(溶解于植物油,配成20 mg·m L^-1混悬液);模型组和正常组给与等体积植物油灌胃,连续给药6周。用Morris水迷宫检测小鼠的认知功能,用逆转录-聚合酶链反应和蛋白质印迹法分别检测海马区NF-κB p65、TNF-α和IL^-1β的基因和蛋白表达水平。结果正常组、模型组和实验组的平均逃避潜伏期分别为(21.49±4.41),(51.69±5.45)和(26.92±4.76)s;正常组、模型组和实验组的穿越平台次数分别为(7.00±0.60),(2.34±0.27)和(4.95±0.54)次;正常组、模型组和实验组的目标象限游泳时间百分比分别为(56.03±3.32)%,(30.71±3.07)%和(46.55±2.73)%;正常组、模型组和实验组的NF-κB p65基因相对表达量分别为0.95±0.05,1.96±0.02和1.42±0.02;正常组、模型组和实验组的TNF-α基因相对表达量分别为0.97±0.04,1.68±0.08和1.32±0.05;正常组、模型组和实验组的IL^-1β基因相对表达量分别为0.97±0.02,1.56±0.03和1.26±0.02。上述指标:模型组与正常组比较,差异均有统计学意义(P<0.05或P<0.01);实验组与模型组比较,差异均有统计学意义(P<0.05或P<0.01)。蛋白结果趋势与基因一致。结论丁苯酞可能通过抑制糖尿病小鼠海马区炎症反应,减轻海马神经元细胞损伤,改善糖尿病小鼠的认知功能。

Objective To investigate the effect of Dl-3-n-butyphthalide on learning and memory function of diabetic db/db mice and the inflammatory response in the hippocampus.Methods Diabetic model db/db mice aged 6 weeks were randomly divided into two groups:Experimental group(Dl-3 n-butyphthalide,120 mg·kg^-1·d^-1)and model group;and db/m mice were set as normal group,8 mice in each group.After 6 weeks of intragastric administration,Morris Water Maze was used to detect the cognitive function of each group.Reverse transcription polymerase chain reaction and Western blot were used to detect the m RNA and protein expressions of nuclear factor Kappa B p65(NF-κB p65),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL^-1β)inthe hippocampus.Results The mean escape latency in normal group,model group and experimental group were(21.49±4.41),(51.69±5.45)and(26.92±4.76)s;times of crossing the platform in normal group,model group and experimental group were(7.00±0.60),(2.34±0.27)and(4.95±0.54)times;the percentage of swimming time of the target quadrant in normal group,model group and experimental group were(56.03±3.32)%,(30.71±3.07)%and(46.55±2.73)%;the m RNA relative expression levels of NF-κB p65 in normal group,model group and experimental group were 0.95±0.05,1.96±0.02 and 1.42±0.02,respectively;the m RNA relative expressions of TNF-αwere 0.97±0.04,1.68±0.08 and 1.32±0.05,respectively;the m RNA relative expressions of IL^-1βwere 0.97±0.02,1.56±0.03 and 1.26±0.02,respectively.Comparison between model group and normal group,the difference of the factors were significantly(P<0.05 or P<0.01);comparison between experimental group and model group,the difference of the factors were significantly(P<0.05 or P<0.01).The trend of protein results is consistent with that of m RNA.Conclusion Dl-3 n-butyphthalide may reduce the damage of hippocampal neurons and improve the cognitive function of diabetic mice by inhibiting the inflammation in hippocampal area.