亚慢性铝暴露对大鼠学习记忆及2-氨基羟甲基恶丙酸受体蛋白表达水平的影响
Effects of Subchronic Aluminum Exposure on Learning and Memory and the Expression of AMPA Receptor in Rats
-
摘要:
目的 研究亚慢性铝暴露对大鼠学习记忆及2-氨基羟甲基恶丙酸(AMPA)受体蛋白表达水平的影响。 方法 健康成年雄性SD大鼠32只,按体重随机分为4组,分别为生理盐水对照组,低、中、高剂量铝染毒组(染毒剂量分别为15、30、45 μmol/kg)。各染毒组腹腔注射麦芽酚铝染毒8周后,采用Morris水迷宫试验检测大鼠空间学习记忆能力，苏木精-伊红(HE)染色观察海马组织病理学改变,Western-blot方法检测大鼠海马组织AMPA受体亚单位谷氨酸受体(GluR)-1、GluR-2和GluR-3的表达量。 结果 HE染色结果显示,随着染铝剂量的增加,海马组织出现锥体层细胞排列紊乱,数目减少,胞核淡染肿胀,轴突走向紊乱等改变。定位航行实验结果显示,低、中、高剂量组及对照组的潜伏期分别为(36.86& #177;3.75)、(44.75& #177;12.82)、(46.48& #177;8.12)、(29.86& #177;10.34) s,中、高剂量组与对照组比较潜伏期增加,差异具有统计学意义(P<0.05)。空间探索实验结果显示,低、中、高剂量组及对照组的目标象限时间分别为(40.58& #177;10.04)、(34.70& #177;9.25)、(32.93& #177;11.28)、(43.11& #177;15.72) s,中、高剂量组与对照组比较目标象限时间降低,差异具有统计学意义(P<0.05)。Western-blot检测结果显示,GluR-1在低、中、高剂量组及对照组的蛋白表达量分别为0.69& #177;0.15、0.54& #177;0.22、0.41& #177;0.14、0.92& #177;0.09,中、高剂量组GluR-1蛋白表达量分别与对照组和低剂量组比较,差异有统计学意义(P<0.05);GluR-2在低、中、高剂量组及对照组的蛋白表达量分别为0.63& #177;0.18、0.62& #177;0.09、0.42& #177;0.09、0.83& #177;0.26,高剂量组GluR-2蛋白表达量与对照组比较,差异有统计学意义(P<0.05)。GluR-3蛋白含量在各组无明显变化。 结论 亚慢性铝暴露可致大鼠学习记忆能力下降,这可能与大鼠海马AMPA受体蛋白表达水平下降有关。 Abstract:Objective To study the effects of subchronic aluminum exposure on learning and memory and the expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor in rats. Methods Thirty-six health adult SD male rats were divided into 4 groups at random, i.e. control, 15 μmol/kg Al(mal)3, 30 μmol/kg Al(mal)3, and 45 μmol/kg Al(mal)3 groups. After intraperitoneal injection of aluminum-maltolate for 8 weeks, the learning and memory abilities of rats were tested by the Morris water maze, the pathology changes of hippocampus were observed with hematoxylin and eosin (HE) staining, and the expressions of GluR-1, GluR-2, and GluR-3 subunits of AMPA receptor in hippocampus were detected by Western blot. Results With the increase of exposure dose, the pyramidal cells in hippocampus significantly decreased in number and were disarranged, with swollen nuclei and disordered axon guidance co-occurred. In the place navigation test, compared with the control group (29.86& #177;10.34)s, the latency to find the platform of the 30 μmol/kg group (44.75& #177;12.82)s and the 45 μmol/kg group (46.48& #177;8.12)s were statistically increased (P<0.05). In the spatial probe test, compared with the control group (43.11& #177;15.72)s, the time spent in target quadrant of the 30 μmol/kg group (34.70& #177;9.25)s and the 45 μmol/kg group (32.93& #177;11.28)s were significantly decreased (P<0.05). Compared with the control group (0.92& #177;0.09, 0.83& #177;0.26), the expressions of GluR-1 and GluR-2 of the 45 μmol/kg group (0.41& #177;0.14, 0.42& #177;0.09) were significantly decreased (P<0.05). Conclusion Subchronic exposure to aluminum could damage the learning and memory of rats, and is possibly related to the expression decrease of AMPA receptors.
下载:
