普仑司特对链佐星诱导的1型糖尿病小鼠记忆损害和神经损伤的影响  

Effect of pranlukast on memory impairment and nerve injury in streptozocin-induced type 1 diabetic mice

作　　者：谈永进[1] 董荣荣[2] 洪浩[2] 

机构地区：[1]安庆医药高等专科学校,安徽安庆246052 [2]中国药科大学药理学教研室,江苏南京210009

出　　处：《中国药理学与毒理学杂志》2016年第4期323-329,共7页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金面上项目(81273497)~~

摘　　要：目的研究半胱氨酰白三烯受体1(Cys LT1R)拮抗剂普仑司特对链佐星(STZ)诱导的1型糖尿病小鼠记忆损害及神经炎症和凋亡的影响。方法选用雄性ICR小鼠,尾静脉注射STZ 150 mg·kg-1制备1型糖尿病小鼠模型。糖尿病小鼠每天ig给予普仑司特,连续给药4周。Morris水迷宫检测小鼠隐藏平台潜伏期、穿台次数及目标象限停留时间;Western蛋白印迹法检测小鼠脑海马和前额叶皮质Cys LT1R,NF-κB p65,白细胞介素1β(IL-1β),肿瘤坏死因子α(TNF-α),剪切胱天蛋白酶3,Bax和Bcl-2蛋白表达水平;测定小鼠的空腹血糖、血清胰岛素含量以及甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDLC)和低密度脂蛋白胆固醇(LDL-C)水平。结果 Morris水迷宫结果显示,与正常对照组比,模型组小鼠逃避潜伏期显著延长,穿台次数和目标象限探索时间均显著降低(P<0.05);给予普仑司特0.6和1.2 mg·kg-1组小鼠逃避潜伏期均显著缩短(P<0.05),穿台次数和目标象限探索时间均显著增加(P<0.05)。Western蛋白印迹结果显示,模型组小鼠海马和前额叶皮质Cys LT1R,NF-κB p65,IL-1β,TNF-α和剪切胱天蛋白酶3蛋白表达以及Bax/Bcl-2比值显著升高(P<0.05);给予普仑司特0.6和1.2 mg·kg-1能显著抑制糖尿病小鼠脑内上述蛋白表达的变化(P<0.05)。但普仑司特对糖尿病小鼠高血糖、低血清胰岛素和脂质代谢紊乱无明显影响。结论普仑司特能够改善STZ诱导的1型糖尿病小鼠学习记忆损害和神经损伤。OBJECTIVE To investigate the effect of pranlukast（Pran）on learning and memory impairment and neuroinflammatory and apoptotic response in streptozocin（STZ）-induced type 1 diabetic mice. METHODS Male ICR mice were injected through the tail vein with STZ（150 mg·kg-1）to induce the type 1 diabetes model. Diabetic mice were administered orally with Pran. After 4 consecutive weeks of administration,the escape latency in hidden platform trials,number of platform crossings and time spent in the target quadrant of mice were assessed by the Morris water maze（MWM）test. Western blot was used to detect the proteins of cysteinyl-leukotrienes receptor-1（Cys LT1R）and pro-inflammatory factors,nuclear factor-κB p65 subunit（NF-κB p65）,interleukin-1β（IL-1β）,tumor necrosis factor-α（TNF-α）,and cleaved caspase 3,Bax and Bcl-2 in the hippocampus and prefrontal cortex of diabetic mice. We also determined fasting blood glucose,serum insulin and lipids such as triglyceride,total cholesterol,high density lipoprotein cholesterol,and low density lipoprotein cholesterol. RESULTS The data of the MWM test showed that untreated diabetic mice displayed a higher escape latency in hidden platform trials（P〈0.05）,and a smaller number of platform crossings（P〈0.05）as well as shorter percentage of time spent in the target quadrant（P〈0.05）. The data of Western blotting showed that treatment with Pran 0.6 and 1.2 mg·kg-1significantly reduced the levels of Cys LT1 R,nuclear NF-κB p65,IL-1β and TNF-α,cleaved caspase 3,and the ratio of Bax and Bcl-2 in the hippocampus and prefrontal cortex of diabetic mice（P〈0.05）. However,Pran did not improve the fasting blood glucose,serum insulin or lipid metabolism disorder in diabetic mice. CONCLUSION Pran improves memory impairment and nerve injury in STZ-induced type 1 diabetic mice.

关 键 词：普仑司特 1型糖尿病 学习记忆 半胱氨酰白三烯受体1 神经炎症 细胞凋亡 

分 类 号：R965[医药卫生—药理学]