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

发布时间：2019-03-11 11:42

【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(P0.05);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(P0.05),穿台次数和目标象限探索时间均显著增加(P0.05)。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(P0.05);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(P0.05)。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。
[Abstract]:Aim to study the effects of Cysteinyl leukotriene receptor 1 (Cys LT1R) antagonist Plenastat on memory impairment, neuroinflammation and apoptosis in type 1 diabetic mice induced by streptozotocin (STZ). Methods male ICR mice were injected with STZ 150 mg kg-1 via caudal vein to establish type 1 diabetic mice model. Ig was given to diabetic mice every day for 4 weeks. The latent period of hidden platform, the number of trays and the stay time of target quadrant in mice were detected by Morris water labyrinth. The expressions of Cys LT1R,NF- kappa B p65, IL-1 尾, TNF- 伪, cystatin 3, Bax and Bcl-2 in hippocampus and prefrontal cortex of mice were detected by Western blot. Fasting blood glucose, serum insulin, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDLC) and low density lipoprotein cholesterol (LDL-C) were measured. Results the results of Morris water maze showed that the escape latency of the model group was significantly longer than that of the normal control group, and the number of trays and the exploration time of the target quadrant were significantly lower than those of the control group (P0.05). The escape latency of mice in the groups of 0.6 and 1.2 mg kg-1 were significantly shortened (P 0.05), and the number of trays and the exploration time of the target quadrant were significantly increased (P 0.05). Western blot analysis showed that the escape latency of the mice was significantly shorter than that of the control group (P < 0.05). In the model group, the expression of Cys LT1R,NF- kappa B p65, IL-1 尾, TNF- 伪, Cystatin-3 protein and the ratio of Bax/Bcl-2 in hippocampus and prefrontal cortex were significantly increased (P0.05). Administration of propranolol 0.6 and 1.2 mg kg-1 significantly inhibited the expression of these proteins in the brain of diabetic mice (P0.05). However, Plenasteride had no significant effect on hyperglycemia, low serum insulin and lipid metabolism disorder in diabetic mice. Conclusion Prednast can improve the learning and memory impairment and nerve injury induced by STZ in type 1 diabetic mice.
【作者单位】：安庆医药高等专科学校;中国药科大学药理学教研室;
【基金】：国家自然科学基金面上项目(81273497)~~
【分类号】：R965

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