CAJ | 학술논문

目的研究亚慢性染铝对断乳大鼠学习记忆和海马细胞内Ca2+及磷脂酶C(phospholipase C,PLC)、N-甲基-D-天冬氨酸受体α(NMDARα)表达的影响,以探讨铝损伤发育中大鼠学习记忆的可能机制.方法刚断乳Wistar大鼠40只,随机分为4组:对照组、低剂量组(饮用含0.2%AlCl3的蒸馏水溶液)、中剂量组(饮用含0.4%AlCl3的蒸馏水溶液)、高剂量组(饮用含0.6%AlCl3的蒸馏水溶液),每组10只.通过饮水亚慢性连续染毒90 d,跳台试验检测仔鼠学习记忆能力,荧光分光光度计法测定细胞内Ca2+浓度,免疫印迹(Western blot)法测定PLC、NMDARα的表达.结果随着染铝剂量的增加,大鼠跳台试验的潜伏期明显缩短,低、中、高剂量组分别为(232.20±57.45)、(35.00±9.37)、(16.10±5.57)s,而错误次数明显增加,低、中、高剂量组分别为(1.10±0.74)、(2.20±0.92)、(3.40±1.51)次,与对照组[分别为(300.00±0.00)s、(0.00±0.00)次]比较,差异均有统计学意义(P<0.05);而海马细胞内[Ca2+]i浓度明显下降,差异亦有统计学意义(P<0.05);低、中、高剂量铝暴露组PLC、NMDARα的表达水平分别为0.30±0.06、0.18±0.04、0.16±0.03,0.38±0.03、0.32±0.02、0.25±0.02,较对照组(分别为0.47±0.07、0.48±0.04)明显降低,差异均有统计学意义(P<0.01).结论亚慢性铝暴露可以引起发育中学习记忆能力的损害,抑制NMDARα及PLC的表达,降低海马细胞内Ca2+水平,推测Ca2+信号系统的紊乱可能是铝损害学习记忆能力的机制之一.
목적 연구아만성염려대단유대서학습기억화해마세포내Ca2+급린지매C(phospholipase C,PLC)、N-갑기-D-천동안산수체α(NMDARα)표체적영향,이탐토려손상발육중대서학습기억적가능궤제.방법 강단유Wistar대서40지,수궤분위4조:대조조、저제량조(음용함0.2%AlCl3적증류수용액)、중제량조(음용함0.4%AlCl3적증류수용액)、고제량조(음용함0.6%AlCl3적증류수용액),매조10지.통과음수아만성련속염독90 d,도태시험검측자서학습기억능력,형광분광광도계법측정세포내Ca2+농도,면역인적(Western blot)법측정PLC、NMDARα적표체.결과 수착염려제량적증가,대서도태시험적잠복기명현축단,저、중、고제량조분별위(232.20±57.45)、(35.00±9.37)、(16.10±5.57)s,이착오차수명현증가,저、중、고제량조분별위(1.10±0.74)、(2.20±0.92)、(3.40±1.51)차,여대조조[분별위(300.00±0.00)s、(0.00±0.00)차]비교,차이균유통계학의의(P<0.05);이해마세포내[Ca2+]i농도명현하강,차이역유통계학의의(P<0.05);저、중、고제량려폭로조PLC、NMDARα적표체수평분별위0.30±0.06、0.18±0.04、0.16±0.03,0.38±0.03、0.32±0.02、0.25±0.02,교대조조(분별위0.47±0.07、0.48±0.04)명현강저,차이균유통계학의의(P<0.01).결론 아만성려폭로가이인기발육중학습기억능력적손해,억제NMDARα급PLC적표체,강저해마세포내Ca2+수평,추측Ca2+신호계통적문란가능시려손해학습기억능력적궤제지일.
Objective To estimate the effect of aluminum on hippocampal intracellular Ca2+ concentration and expression of phospholipase C (PLC) and NMDA receptor α (NMDARα) genes in hippocampus as well as the neural behaviors in weaning rats through subchronic exposure in order to explore the mechanism which aluminum impaired the ability of learning and memory of central nervous system development. Methods Weaning Wistar rats were randomly divided into four groups based on their body weight. Aluminium chloride was administered by water at the doses of 0.2%, 0.4% and 0.6% (m/v) for 90 days. Platform experiment was used to detect the activity of learning and memory. Fura-2/AM calcium ions fluorescence indicator was used to measure Ca2+ concentration in hippocampal neurons. Western blot method was used to detect the expressions of PLC and NMDARα genes. Results The incubation of rats in platform experiment [(232.20±57.45), ( 35.00±9.37 ), (16.10±5.57) s] shortened while increase of mistake times (1.10±0.74, 2.20±0.92,3.40± 1.51 ) was significantly associated with the dose of aluminum (P<0.01 ). The Ca2+ concentration decreased significantly in the rats of aluminum exposed groups (P<0.01). The expression of PLC and NMDARα in aluminum exposed groups (0.30±0.06, 0.18±0.04, 0.16±0.03 ; 0.38±0.03, 0.32±0.02, 0.25±0.02) decreased significantly compared with that in the control group (0.47±0.07,0.48±0.04) (P<0.01 ) and there was a dose-effect relationship in the NMDARα expression. Conclusion Subchronic exposure of aluminium could impair the ability of learning and memory in rats during development, inhibit the expression of NMDARα and PLC and reduce Ca2+ concentration, suggesting that the disorder of Ca2+ signaling system might be one of mechanisms of aluminium damaging the ability of learning and memory.