IL-33对阿尔茨海默病模型大鼠脑组织内β-淀粉样蛋白的清除作用及其机制

doi:10.13481/j.1671-587x.20180504

摘要/Abstract

摘要： 目的：探讨白细胞介素33（IL-33）对阿尔茨海默病（AD）模型大鼠学习记忆能力和脑组织内β-淀粉样蛋白（Aβ）和Ⅱ型辅助性T细胞（Th2）水平的影响，阐明IL-33对AD模型大鼠脑组织内Aβ的清除作用及其机制。方法：70只雄性SD大鼠随机分为正常对照组（皮下注射生理盐水，灌胃双蒸水），模型组，假手术组，极低、低、中和高剂量IL-33组（0.01、0.10、1.00和10.00 mg·L^-1），每组10只。除正常对照组外，其余各组大鼠皮下注射D-半乳糖和灌胃AlCl₃，每日1次，连续60 d。末次给药后，进行大鼠跳台实验和Morris水迷宫实验，观察大鼠的潜伏期、错误次数、逃避潜伏期、目标象限停留时间和游泳距离。行为学检测结束后，IL-33各剂量组大鼠侧脑室注射相应剂量IL-33，假手术组大鼠侧脑室注射生理盐水。采用ELISA法检测各组大鼠脑组织内Aβ和Th2水平。结果：跳台实验，与正常对照组比较，模型组大鼠的错误次数增多（t=8.154，P<0.01），潜伏期明显缩短（t=4.579，P<0.01）；Morris水迷宫实验，与正常对照组比较，模型组大鼠逃避潜伏期明显延长（t=27.810，P<0.01），在目标象限内滞留时间和游泳距离明显缩短（t=3.767，P<0.01；t=1.973，P<0.05）。ELISA法检测，模型组大鼠脑组织中Aβ水平较正常对照组明显升高（t=3.222，P<0.05），低、中和高剂量IL-33组大鼠脑组织内Aβ水平较模型组明显降低（P<0.05）；模型组大鼠脑组织内Th2水平较正常对照组明显降低（t=4.646，P<0.01），低、中和高剂量IL-33组大鼠脑组织内Th2水平较模型组明显升高（P<0.05）。结论：IL-33对AD模型大鼠脑组织内Aβ有清除作用，其作用机制可能与提高大鼠脑组织内Th2水平有关。

关键词: 白细胞介素33, 阿尔茨海默病, β-淀粉样蛋白, Ⅱ型辅助性T细胞, 大鼠,SD

Abstract: Objective:To explore the influence of interleukin-33(IL-33) on the abilities of spatial learning and memory and the levels of amyloid β-protein(Aβ) and helper T cell 2 (Th2) in the model rats with Alzheimer's disease (AD),and to clarify the effect of IL-33 in the scavenging of Aβ in brain tissue of the model rats with AD and its mechanism. Methods:A total of 70 SD male rats were randomly divided into normal control group (intragastrical administration of double steaming water and subcutaneous injection of D-galactose),model group,sham operation group and extremely low dose,low dose,middle dose,high dose(0.01,0.10,1.00,and 10.00 mg·L^-1) of IL-33 groups (intragastrical administration of AlCl₃ and subcutaneous injection of D-galactose);10 rats in each group. The agents were administered once daily for 60 d. After the last administration,step down test and Morris water maze experiment were used to detect the latency,the mistake times,the escape latencies,the resident time in target quadrant,and the swimming distance. After the behavioral testing,IL-33 was injected intracerebroventricularly for each dose of IL-33 group,and saline was injected intracerebroventricularly in the rats in sham operation group. ELISA method was used to detect the levels of Aβ and Th2 in brain tissue of the rats. Results:The results of step down test showed that the latency of the rats in model group was obviously shortened (t=8.154,P<0.01) and the mistake times were significantly increased compared with normal control group(t=4.579,P<0.01).The results of Morris water maze test showed that the escape latency was obviously prolonged(t=27.810,P<0.01),the resident time in target quadrant and the distance of swimming of the rats in model group were significantly reduced compared with normal control group(t=3.767,P<0.01;t=1. 973,P<0.05).The ELISA results showed that the level of Aβ in brain tissue of the rats in model group was significantly increased (t=3.222,P<0.05) compared with normal control group,and the levels of Aβ in the brain tissue of the rats in low,middle and high doses of IL-33 groups were significantly reduced compared with model group (P<0.05).The level of Th2 in brain tissue of the rats in model group was significantly decreased compared with normal control group(t=4.646,P<0.01), and the levels of Th2 in brain tissue of the rats in low,middle and high doses of IL-33 groups were significantly increased compared with model group (P<0.05). Conclusion:IL-33 has a scavenging effect on Aβ in brain tissue of the AD model rats,and its mechanism may be related to the increase of Th2level in brain tissue of the rats.

Key words: interleukin-33, Alzheimer's disease, amyloid β-protein, type Ⅱ helper T cell, rats,SD

中图分类号:

R749

李军, 姚静, 王国芳, 辛勤, 崔立坤, 齐汝霞. IL-33对阿尔茨海默病模型大鼠脑组织内β-淀粉样蛋白的清除作用及其机制[J]. 吉林大学学报(医学版), 2018, 44(05): 908-913.

LI Jun, YAO Jing, WANG Guofang, XIN Qin, CUI Likun, QI Ruxia. Clearance effect of IL-33 on amyloid β-protein in brain tissue of modelrats with Alzheimer's disease and its mechanism[J]. Journal of Jilin University(Medicine Edition), 2018, 44(05): 908-913.

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