甲基汞暴露对出生后大鼠学习记忆及NMDA受体表达的影响

[目的]研究甲基汞暴露对出生后不同生长期大鼠学习记忆能力及N-甲基0．天冬氨酸（NMDA）受体mRNA水平表达的影响。[方法]将出生后大鼠随机分组,即5mL／kg生理盐水组和5mg／kg氯化甲基汞（MMC）染毒组,其中染毒组按生后不同生长时期分4个亚组,即PND7、PND14、PND28和PND60组,连续7d灌胃染毒。采用Morris水迷宫试验检测大鼠学习记忆功能的改变,用原子荧光光度计检测脑组织汞含量、用逆转录一聚合酶链式反应（RT-PCR）特异性扩增受体NMDA的2A、2B、2C亚基,半定量分析PCR产物凝胶电泳结果。[结果]各染毒亚组在染毒后脑组织中汞含量明显高于对照组（P〈0．01）,水迷宫试验后,PND28皮质组织及PND60脑组织中汞含量明显高于对照组（P〈0．01）;Morris水迷宫试验结果显示,PND7、PND14染毒大鼠水迷宫测试潜伏期明显长于对照组（P〈0．01）;PND14染毒亚组海马和皮质中NR2AmRNA的表达明显低于对照组（P〈0．05）;PND14染毒亚组海马中NR2BmRNA表达明显低于对照组（P〈0．01）;PND14染毒亚组海马和皮质以及PND28亚组皮质中NR2CmRNA表达明显高于对照组（P〈0．01）.[结论]甲基汞对出生后1、2周的大鼠学习记忆功能有明显影响,其影响与脑组织NMDA受体2亚基mRNA表达变化有关。     

铅影响学习记忆的研究进展

本文综述了铅影响学习记忆的研究现状 ,铅可破坏 N-甲基 - D-天冬氨酸受体的结构和功能 ,影响递质谷氨酸的合成、释放和灭活 ;干扰 c AMP、Ca2 等第二信使的作用和功能 ,改变蛋白激酶和钙调蛋白的活性及分布 ;抑制一氧化氮等逆行信使的合成 ,还可影响调节学习记忆的多种神经递质或神经肽。最终阻碍长时程增强效应的形成 ,影响学习记忆 ;使患者记忆力减退、反应迟钝、学习困难、早老或痴呆。     

染铝对断乳大鼠学习记忆及海马细胞内Ca2+及磷脂酶和N-甲基-D-天冬氨酸受体α表达的影响

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.     

全氟辛烷磺酸对大鼠仔鼠学习记忆能力的影响

目的 观察出生前后全氟辛烷磺酸(PFOS)暴露对大鼠仔鼠空间学习记忆能力以及大脑皮质和海马结构中N-甲基-D-门冬氨酸受体2B(NR2B)亚单位mRNA和蛋白水平的影响,探讨PFOS所致神经发育毒性机制.方法 应用数字表法将28只受孕Wistar大鼠按3:2:2比例随机分配到对照(C)、低剂量(L)和高剂量(H)组,大鼠从妊娠第0天开始分别自由摄食含0、7.2、14.4 mg/kg PFOS的粉末状饲料进行连续染毒至仔鼠出生后30 d.采用交叉哺育的方法,建立仔鼠出生前后均不暴露(CC)、仅出生前暴露(LC和HC)、仅出生后暴露(CL和CH)、出生前后均暴露(LL和HH)于PFOS的动物模型.水迷宫实验检测仔鼠空间学习和记忆能力,半定量反转录聚合酶链反应(RT-PCR)法检测仔鼠大脑额叶皮质NR2B mRNA水平,免疫组织化学染色法观察仔鼠大脑皮质(额叶及颞叶皮质)和海马组织(CA1、CA3、CA4和DG区)中NR2B蛋白的表达情况.结果 水迷宫实验洲练第4天时CL、CH、LL和HH组仔鼠逃避潜伏期分别为(99.83±25.77)s、(111.30±17.82)s、(106.40±18.71)s、(107.70±16.85)s,显著长于CC组[(54.90±26.69)s](q值分别为4.349、4.773、6.026、5.641,P值均<0.01);训练第4天时HH组仔鼠进入盲端的错误次数为(22.30±7.56)次,显著高于Cc组[(9.80±4.64)次](q=5.173,P<0.01).出生后第l天(postnatal day 1,PND1)HC组和PND14时LC组、HC组、HH组仔鼠大脑额叶皮质中NR2B mRNA水平分别为(0.167±0.008)、(0.364±0.035)、(0.341±0.030)、(0.328±0.045),均显著低于CC组的(0.271±0.060)和(0.465±0.067),差异有统计学意义(q值分别为3.547、3.739、4.597、5.006,P值均<0.05).PNDI时LC组仔鼠海马CA1区NR2B蛋白水平为(0.091±0.005),显著低于CC组(0.123±0.009)(q=5.209,P<0.05);PND14时,PFOS的影响扩大到仔鼠大脑皮质和海马结构各区;PND28时PFOS的影响见于CA1、CA3和颞叶皮质区.结论 出生前后不同时期PFOS暴露导致大鼠仔鼠空间学习和记忆能力损伤,其机制可能为大脑皮质和海马结构各区NR2B表达水平的降低.     

全氟辛烷磺酸对大鼠仔鼠学习记忆能力的影响

Objective To study the effects of prenatal and postnatal perfluorooetane sulfonate (PFOS) exposure on spatial learning and memory, N-methyl-D-aspartate receptor 2B (NR2B) mRNA and protein level in frontal cortex and hippoeampus of rat pups and to explore the mechanism of developmental neurotoxicity induced by PFOS. Methods Twenty-eight pregnant mrs were randomly divided into three groups in proportion of 3: 2: 2,including control group (C), low dose group (L) and high dose group (H) by means of randomized number table, which respectively received 0,7.2, 14.4 mg/kg PFOS feed from pregnancy day 0 to postnatal day(PND)30 by free feedings. The animal models of prenatal and postnatal non-exposure (CC), prenatal exposure (LC and HC), postnatal exposure (CL and CH), and prenatal and postnatal exposure (LL and HH) to PFOS were established by cross-fostering method. The spatial learning and memory were measured by water maze experiment,the NR2B mRNA levels in frontal cortex of rat pups was determined with semi-quantitative RT-PCR, NR2B protein express in cerebral cortex (frontal and tempera]cortex) and hippocampus (CAI, CA3, CA4 and DG regions) of rat pups was detected by immunohistochemistry. Results The escape latency of CL, CH, LL and HH groups pups in water maze experiment were (99. 83±25.77) s, (111.30±17. 82) s, (106. 40±18. 71) s, (107.70±16. 85) s, and longer as compared with CC group[(54.90±26.69)s](q value were 4.349,4.773,6.026 and 5.641, respectively,P<0. 01). The number of errors of HH group rat pups entering dead end was (22. 30±7.56) at the training day 4,and it was significantly higher than that of CC group (9. 80±4. 64) (q=5. 173,P<0. 01). The NR2B mRNA levels of frontal cortex of pups in HC group at PND1 ,and LC group, HC group and HH group at PND14 were (0. 167±0. 008), (0. 364±0. 035), (0. 341±0. 030) and (0. 328±0. 045) respectively,which were significantly lower than CC group (0.271±0.060) and (0.465±0.067) (q values were 3. 547, 3. 739, 4. 597 and 5. 006, respectively, P<0.05) . The results of immunohistochemistry indicated that NR2B protein express of the hippocampus CA1 region of pups in LC group was (0.091±0.005),and showed significant lower than CC group which was (0. 123±0.009) at PND1 (q=5. 209 ,P<0. 05). At PND14, the effect of PFOS extended to cerebral cortex and hippocampus regions. At PND28, the effects of PFOS were showed in hippocampus CA1, CA3 and temporal cortex regions. Conclusion Prenatal and postnatal exposure to PFOS should result in the spatial learning and memory damage,and the mechanism might be possibly involved in the decrease of NR2B level in cerebra lcortex and hippocampal formation regions.     

全氟辛烷磺酸对大鼠仔鼠学习记忆能力的影响

Objective To study the effects of prenatal and postnatal perfluorooetane sulfonate (PFOS) exposure on spatial learning and memory, N-methyl-D-aspartate receptor 2B (NR2B) mRNA and protein level in frontal cortex and hippoeampus of rat pups and to explore the mechanism of developmental neurotoxicity induced by PFOS. Methods Twenty-eight pregnant mrs were randomly divided into three groups in proportion of 3: 2: 2,including control group (C), low dose group (L) and high dose group (H) by means of randomized number table, which respectively received 0,7.2, 14.4 mg/kg PFOS feed from pregnancy day 0 to postnatal day(PND)30 by free feedings. The animal models of prenatal and postnatal non-exposure (CC), prenatal exposure (LC and HC), postnatal exposure (CL and CH), and prenatal and postnatal exposure (LL and HH) to PFOS were established by cross-fostering method. The spatial learning and memory were measured by water maze experiment,the NR2B mRNA levels in frontal cortex of rat pups was determined with semi-quantitative RT-PCR, NR2B protein express in cerebral cortex (frontal and tempera]cortex) and hippocampus (CAI, CA3, CA4 and DG regions) of rat pups was detected by immunohistochemistry. Results The escape latency of CL, CH, LL and HH groups pups in water maze experiment were (99. 83±25.77) s, (111.30±17. 82) s, (106. 40±18. 71) s, (107.70±16. 85) s, and longer as compared with CC group[(54.90±26.69)s](q value were 4.349,4.773,6.026 and 5.641, respectively,P<0. 01). The number of errors of HH group rat pups entering dead end was (22. 30±7.56) at the training day 4,and it was significantly higher than that of CC group (9. 80±4. 64) (q=5. 173,P<0. 01). The NR2B mRNA levels of frontal cortex of pups in HC group at PND1 ,and LC group, HC group and HH group at PND14 were (0. 167±0. 008), (0. 364±0. 035), (0. 341±0. 030) and (0. 328±0. 045) respectively,which were significantly lower than CC group (0.271±0.060) and (0.465±0.067) (q values were 3. 547, 3. 739, 4. 597 and 5. 006, respectively, P<0.05) . The results of immunohistochemistry indicated that NR2B protein express of the hippocampus CA1 region of pups in LC group was (0.091±0.005),and showed significant lower than CC group which was (0. 123±0.009) at PND1 (q=5. 209 ,P<0. 05). At PND14, the effect of PFOS extended to cerebral cortex and hippocampus regions. At PND28, the effects of PFOS were showed in hippocampus CA1, CA3 and temporal cortex regions. Conclusion Prenatal and postnatal exposure to PFOS should result in the spatial learning and memory damage,and the mechanism might be possibly involved in the decrease of NR2B level in cerebra lcortex and hippocampal formation regions.     

全氟辛烷磺酸对大鼠仔鼠学习记忆能力的影响

Objective To study the effects of prenatal and postnatal perfluorooetane sulfonate (PFOS) exposure on spatial learning and memory, N-methyl-D-aspartate receptor 2B (NR2B) mRNA and protein level in frontal cortex and hippoeampus of rat pups and to explore the mechanism of developmental neurotoxicity induced by PFOS. Methods Twenty-eight pregnant mrs were randomly divided into three groups in proportion of 3: 2: 2,including control group (C), low dose group (L) and high dose group (H) by means of randomized number table, which respectively received 0,7.2, 14.4 mg/kg PFOS feed from pregnancy day 0 to postnatal day(PND)30 by free feedings. The animal models of prenatal and postnatal non-exposure (CC), prenatal exposure (LC and HC), postnatal exposure (CL and CH), and prenatal and postnatal exposure (LL and HH) to PFOS were established by cross-fostering method. The spatial learning and memory were measured by water maze experiment,the NR2B mRNA levels in frontal cortex of rat pups was determined with semi-quantitative RT-PCR, NR2B protein express in cerebral cortex (frontal and tempera]cortex) and hippocampus (CAI, CA3, CA4 and DG regions) of rat pups was detected by immunohistochemistry. Results The escape latency of CL, CH, LL and HH groups pups in water maze experiment were (99. 83±25.77) s, (111.30±17. 82) s, (106. 40±18. 71) s, (107.70±16. 85) s, and longer as compared with CC group[(54.90±26.69)s](q value were 4.349,4.773,6.026 and 5.641, respectively,P<0. 01). The number of errors of HH group rat pups entering dead end was (22. 30±7.56) at the training day 4,and it was significantly higher than that of CC group (9. 80±4. 64) (q=5. 173,P<0. 01). The NR2B mRNA levels of frontal cortex of pups in HC group at PND1 ,and LC group, HC group and HH group at PND14 were (0. 167±0. 008), (0. 364±0. 035), (0. 341±0. 030) and (0. 328±0. 045) respectively,which were significantly lower than CC group (0.271±0.060) and (0.465±0.067) (q values were 3. 547, 3. 739, 4. 597 and 5. 006, respectively, P<0.05) . The results of immunohistochemistry indicated that NR2B protein express of the hippocampus CA1 region of pups in LC group was (0.091±0.005),and showed significant lower than CC group which was (0. 123±0.009) at PND1 (q=5. 209 ,P<0. 05). At PND14, the effect of PFOS extended to cerebral cortex and hippocampus regions. At PND28, the effects of PFOS were showed in hippocampus CA1, CA3 and temporal cortex regions. Conclusion Prenatal and postnatal exposure to PFOS should result in the spatial learning and memory damage,and the mechanism might be possibly involved in the decrease of NR2B level in cerebra lcortex and hippocampal formation regions.     

全氟辛烷磺酸对大鼠仔鼠学习记忆能力的影响

Objective To study the effects of prenatal and postnatal perfluorooetane sulfonate (PFOS) exposure on spatial learning and memory, N-methyl-D-aspartate receptor 2B (NR2B) mRNA and protein level in frontal cortex and hippoeampus of rat pups and to explore the mechanism of developmental neurotoxicity induced by PFOS. Methods Twenty-eight pregnant mrs were randomly divided into three groups in proportion of 3: 2: 2,including control group (C), low dose group (L) and high dose group (H) by means of randomized number table, which respectively received 0,7.2, 14.4 mg/kg PFOS feed from pregnancy day 0 to postnatal day(PND)30 by free feedings. The animal models of prenatal and postnatal non-exposure (CC), prenatal exposure (LC and HC), postnatal exposure (CL and CH), and prenatal and postnatal exposure (LL and HH) to PFOS were established by cross-fostering method. The spatial learning and memory were measured by water maze experiment,the NR2B mRNA levels in frontal cortex of rat pups was determined with semi-quantitative RT-PCR, NR2B protein express in cerebral cortex (frontal and tempera]cortex) and hippocampus (CAI, CA3, CA4 and DG regions) of rat pups was detected by immunohistochemistry. Results The escape latency of CL, CH, LL and HH groups pups in water maze experiment were (99. 83±25.77) s, (111.30±17. 82) s, (106. 40±18. 71) s, (107.70±16. 85) s, and longer as compared with CC group[(54.90±26.69)s](q value were 4.349,4.773,6.026 and 5.641, respectively,P<0. 01). The number of errors of HH group rat pups entering dead end was (22. 30±7.56) at the training day 4,and it was significantly higher than that of CC group (9. 80±4. 64) (q=5. 173,P<0. 01). The NR2B mRNA levels of frontal cortex of pups in HC group at PND1 ,and LC group, HC group and HH group at PND14 were (0. 167±0. 008), (0. 364±0. 035), (0. 341±0. 030) and (0. 328±0. 045) respectively,which were significantly lower than CC group (0.271±0.060) and (0.465±0.067) (q values were 3. 547, 3. 739, 4. 597 and 5. 006, respectively, P<0.05) . The results of immunohistochemistry indicated that NR2B protein express of the hippocampus CA1 region of pups in LC group was (0.091±0.005),and showed significant lower than CC group which was (0. 123±0.009) at PND1 (q=5. 209 ,P<0. 05). At PND14, the effect of PFOS extended to cerebral cortex and hippocampus regions. At PND28, the effects of PFOS were showed in hippocampus CA1, CA3 and temporal cortex regions. Conclusion Prenatal and postnatal exposure to PFOS should result in the spatial learning and memory damage,and the mechanism might be possibly involved in the decrease of NR2B level in cerebra lcortex and hippocampal formation regions.     

全氟辛烷磺酸对大鼠仔鼠学习记忆能力的影响

Objective To study the effects of prenatal and postnatal perfluorooetane sulfonate (PFOS) exposure on spatial learning and memory, N-methyl-D-aspartate receptor 2B (NR2B) mRNA and protein level in frontal cortex and hippoeampus of rat pups and to explore the mechanism of developmental neurotoxicity induced by PFOS. Methods Twenty-eight pregnant mrs were randomly divided into three groups in proportion of 3: 2: 2,including control group (C), low dose group (L) and high dose group (H) by means of randomized number table, which respectively received 0,7.2, 14.4 mg/kg PFOS feed from pregnancy day 0 to postnatal day(PND)30 by free feedings. The animal models of prenatal and postnatal non-exposure (CC), prenatal exposure (LC and HC), postnatal exposure (CL and CH), and prenatal and postnatal exposure (LL and HH) to PFOS were established by cross-fostering method. The spatial learning and memory were measured by water maze experiment,the NR2B mRNA levels in frontal cortex of rat pups was determined with semi-quantitative RT-PCR, NR2B protein express in cerebral cortex (frontal and tempera]cortex) and hippocampus (CAI, CA3, CA4 and DG regions) of rat pups was detected by immunohistochemistry. Results The escape latency of CL, CH, LL and HH groups pups in water maze experiment were (99. 83±25.77) s, (111.30±17. 82) s, (106. 40±18. 71) s, (107.70±16. 85) s, and longer as compared with CC group[(54.90±26.69)s](q value were 4.349,4.773,6.026 and 5.641, respectively,P<0. 01). The number of errors of HH group rat pups entering dead end was (22. 30±7.56) at the training day 4,and it was significantly higher than that of CC group (9. 80±4. 64) (q=5. 173,P<0. 01). The NR2B mRNA levels of frontal cortex of pups in HC group at PND1 ,and LC group, HC group and HH group at PND14 were (0. 167±0. 008), (0. 364±0. 035), (0. 341±0. 030) and (0. 328±0. 045) respectively,which were significantly lower than CC group (0.271±0.060) and (0.465±0.067) (q values were 3. 547, 3. 739, 4. 597 and 5. 006, respectively, P<0.05) . The results of immunohistochemistry indicated that NR2B protein express of the hippocampus CA1 region of pups in LC group was (0.091±0.005),and showed significant lower than CC group which was (0. 123±0.009) at PND1 (q=5. 209 ,P<0. 05). At PND14, the effect of PFOS extended to cerebral cortex and hippocampus regions. At PND28, the effects of PFOS were showed in hippocampus CA1, CA3 and temporal cortex regions. Conclusion Prenatal and postnatal exposure to PFOS should result in the spatial learning and memory damage,and the mechanism might be possibly involved in the decrease of NR2B level in cerebra lcortex and hippocampal formation regions.     

全氟辛烷磺酸对大鼠仔鼠学习记忆能力的影响

Objective To study the effects of prenatal and postnatal perfluorooetane sulfonate (PFOS) exposure on spatial learning and memory, N-methyl-D-aspartate receptor 2B (NR2B) mRNA and protein level in frontal cortex and hippoeampus of rat pups and to explore the mechanism of developmental neurotoxicity induced by PFOS. Methods Twenty-eight pregnant mrs were randomly divided into three groups in proportion of 3: 2: 2,including control group (C), low dose group (L) and high dose group (H) by means of randomized number table, which respectively received 0,7.2, 14.4 mg/kg PFOS feed from pregnancy day 0 to postnatal day(PND)30 by free feedings. The animal models of prenatal and postnatal non-exposure (CC), prenatal exposure (LC and HC), postnatal exposure (CL and CH), and prenatal and postnatal exposure (LL and HH) to PFOS were established by cross-fostering method. The spatial learning and memory were measured by water maze experiment,the NR2B mRNA levels in frontal cortex of rat pups was determined with semi-quantitative RT-PCR, NR2B protein express in cerebral cortex (frontal and tempera]cortex) and hippocampus (CAI, CA3, CA4 and DG regions) of rat pups was detected by immunohistochemistry. Results The escape latency of CL, CH, LL and HH groups pups in water maze experiment were (99. 83±25.77) s, (111.30±17. 82) s, (106. 40±18. 71) s, (107.70±16. 85) s, and longer as compared with CC group[(54.90±26.69)s](q value were 4.349,4.773,6.026 and 5.641, respectively,P<0. 01). The number of errors of HH group rat pups entering dead end was (22. 30±7.56) at the training day 4,and it was significantly higher than that of CC group (9. 80±4. 64) (q=5. 173,P<0. 01). The NR2B mRNA levels of frontal cortex of pups in HC group at PND1 ,and LC group, HC group and HH group at PND14 were (0. 167±0. 008), (0. 364±0. 035), (0. 341±0. 030) and (0. 328±0. 045) respectively,which were significantly lower than CC group (0.271±0.060) and (0.465±0.067) (q values were 3. 547, 3. 739, 4. 597 and 5. 006, respectively, P<0.05) . The results of immunohistochemistry indicated that NR2B protein express of the hippocampus CA1 region of pups in LC group was (0.091±0.005),and showed significant lower than CC group which was (0. 123±0.009) at PND1 (q=5. 209 ,P<0. 05). At PND14, the effect of PFOS extended to cerebral cortex and hippocampus regions. At PND28, the effects of PFOS were showed in hippocampus CA1, CA3 and temporal cortex regions. Conclusion Prenatal and postnatal exposure to PFOS should result in the spatial learning and memory damage,and the mechanism might be possibly involved in the decrease of NR2B level in cerebra lcortex and hippocampal formation regions.     

妊娠压力与铅联合暴露对大鼠子代空间学习记忆的影响

目的 探讨妊娠压力与铅联合暴露对大鼠子代早期空间学习记忆能力的影响.方法 运用数字表法随机将32只Sprague-Dawley孕鼠分为空白对照组(NS/C),铅暴露组(NS/L),压力暴露组(S/C),联合暴露组(S/L),每组8只.NS/L、S/L自由饮用0.2%醋酸铅溶液,S/C、S/L给予束缚压力.子代于30 d龄进行Morris水迷宫测试,并检测海马组织铅含量及水迷宫实验前、后血清肾上腺酮.结果 S/L雄、雌性仔鼠在原平台所在象限停留时间分别为(16.08 ±3.41)s、(15.72 ±3.33)s,显著短于NS/L(25.42±4.76)s、(24.55±4.43)s和S/C(20.96±3.45)s、(20.65±2.98)s,妊娠压力与铅对仔鼠在原平台所在象限停留时间的影响存在交互作用(F=5.478,P<0.05);妊娠压力与铅对仔鼠应激后血清肾上腺酮水平的影响存在交互作用.NS/L、S/L仔鼠海马铅含量分别为(0.4378 ±0.1041)μg/g、(0.4679 ±0.1243)μg/g,差异无统计学意义(F=0.298,P0.05).结论 (1)妊娠压力与铅对大鼠子代学习记忆的损害可能具有叠加作用.(2)妊娠压力与铅对仔鼠下丘脑.垂体-肾上腺轴的影响可能具有叠加作用.该作用可能是二者对子代学习记忆叠加损害的原因之一.(3)联合暴露未显著增加铅在子代海马中的蓄积.     

铅对仔鼠学习记忆及其海马中突触体相关蛋白-25基因和蛋白表达的影响

目的 探讨母体铅染毒对仔鼠学习记忆及海马中突触体相关蛋白-25(SNAP-25)mRNA 表达的影响.方法 雌性小鼠自妊娠第1天开始经饮水染铅(0.3、1.0、3.0g/L),对照组饮蒸馏水,至仔鼠出生后21 d断乳为止.随机抽取各组仔鼠,在出生后第7、14、21天分别测其血液和海马组织中铅的含量;在出生后第21天时,进行水迷宫试验,分别采用反转录-聚合酶链反应和免疫组化方法测定各组海马组织中SNAP-25 mRNA和蛋白的表达.结果 与对照组比较,各剂量染铅组血液、海马组织中铅含量均明显升高,差异均有统计学意义(P<0.05).仔鼠错误次数有随母鼠染铅剂量增加而增加的趋势,1.0、3.0g/L组错误次数分别为5.89±0.54、9.53±1.03,与对照组(1.73±0.07)比较,差异有统计学意义(P<0.05,P<0.01).与对照组相比,染铅组海马中SNAP-25 mRNA和蛋白表达明显降低,差异均有统计学意义(P<0.05).结论 母体铅暴露可导致仔鼠学习记忆功能损害,铅下调SNAP-25 mRNA的表达,可能影响了突触前末梢神经递质的释放,造成神经系统的损害.     

职业性铅暴露工人血铅和血尿酸的相关性分析

目的 研究职业性铅作业工人血铅和尿酸的变化,探讨血铅浓度变化和血尿酸指标之间的关系.方法 车间空气中铅烟的短时间接触浓度用原子吸收火焰法检测.选择一般情况可比的非铅作业工人作为对照,根据接触铅的浓度是否超过职业限值将263名铅接触工人分为职业限值内组及超职业限值组.分析不同血铅水平和血尿酸指标的变化.结果 (1)车间空气中铅烟的时间加权平均容许浓度(PC-TWA)达0.13 mg/m3,超标率为68.61％; (2)接铅超职业限值组血铅浓度达(3.16±0.03) μmol/L、尿酸为(528±109.48) μmol/L,均显著高于对照组(P＜0.05); (3)血铅浓度的变化和尿酸异常率存在一致的变化趋势.结论 职业性铅接触引起血铅浓度升高和血尿酸升高,且血铅浓度越高,血尿酸升高程度越大.     

孕期补锌对胎儿生长受限仔鼠学习记忆能力改变的研究

目的探讨孕期补锌对胎儿生长受限(fetal growth restriction,FGR)仔鼠空间学习记忆能力的影响。方法建造SD孕鼠FGR模型,孕鼠随机分为3组(FGR组10只、模型组10只和正常组11只),模型组喂养添锌饲料,另两组喂养普通饲料。从3组孕鼠中分别随机抽取10只仔鼠作为研究对象(FGR组、模型组均抽取FGR仔鼠)分别于生后1、2、4月进行Morris水迷宫的定位航行实验及空间探索实验,检测FGR子代空间学习记忆能力的改变。结果 1、2、4月龄模型组在水迷宫任务中更多采取有效策略,明显优于FGR组(P0.05),与对照组间差异无统计学意义(P0.05)。1、2、4月龄,三组仔鼠的逃避潜伏期随着训练次数的增加而缩短(P0.05)。1、2、4月龄模型组仔鼠的平均潜伏期较对照组明显增长,差异有统计学意义(P均0.05)。除4月龄外,模型组仔鼠的平均潜伏期较FGR组明显缩短,站台停留时间较FGR组明显延长(P0.05),4月龄FGR组、模型组仔鼠站台象限停留时间无统计学意义(P0.05)。结论孕期补锌能够改善FGR子代大鼠的水迷宫测试成绩,提示孕期补锌对于FGR引起的幼鼠空间学习能力受损有一定的保护作用;出生后行为训练对FGR造成的脑损害可能有一定的纠正作用。     

天麻和阿胶对铅所致大鼠海马结构及功能损害的保护作用

目的　探讨天麻和阿胶对亚慢性铅中毒所致海马超微结构及学习记忆功能损害的保护作用。方法　对大鼠进行亚慢性醋酸铅染毒 (0 .2g·kg- 1 ·d- 1 ) ,实验组分别给予天麻 (4g·kg- 1 ·d- 1 )、阿胶 (1g·kg- 1 ·d- 1 )或天麻、阿胶联合应用 ,监测血铅浓度 ,利用Y型迷宫测定各组学习记忆功能 ,并利用透射电镜技术观察各组海马CA3区锥体细胞的超微结构。结果　各染铅组大鼠血铅浓度 (染铅组 690 .6μg/L ,铅 +天麻组 688.8μg/L ,铅 +阿胶组 663 .8μg/L ,铅 +天麻 +阿胶组 667.2 μg/L)均高于对照组 (2 8.2 4 μg/L ) ,差异有显著性 (P <0 .0 1 ) ;但各染铅组之间差异无显著性 (P >0 .0 5)。Y型迷宫试验中 ,铅使大鼠达标前所受电击次数明显增加 ,与对照组比较 ,差异有显著性 (P <0 .0 1 )。天麻和阿胶单用可减少染铅大鼠达标前所受电击次数 (P <0 .0 5 ,P <0 .0 1 )。二者联合应用较之单独应用使电击次数减少更明显 (P <0 .0 1 )。海马组织电镜下观察 :正常对照组海马CA3区锥体细胞电镜下未见异常 ;铅染毒组则明显异常 ,出现核分离等现象 ;铅 +天麻组发现巨大线粒体等应激反应的表现 ,铅 +阿胶组海马组织表现轻微异常 ;铅 +天麻 +阿胶组海马组织基本正常 ,也出现巨大线粒体等代偿性反应。结论　天麻、阿     

铅暴露对仔鼠学习记忆能力及发育早期海马组织中N-甲基-D天门冬氨酸受体亚单位表达的影响

目的探讨铅暴露对仔鼠学习记忆能力及发育早期各阶段海马组织中N-甲基-D天门冬氨酸(NMDA)亚单位表达的影响。方法将24只清洁级妊娠昆明小鼠随机分为4组,分别为对照(蒸馏水)组及0.5、1.0、2.0 g/L铅暴露组,每组6只。采用自由饮水方式进行染毒,母鼠从妊娠第1天起开始饮用含铅水,仔鼠于出生后(PND)21天断乳,继续饮含铅水至实验结束。水迷宫测定PND 40仔鼠学习记忆能力;并分别于PND10、PND20和PND40,测定海马组织中NMDA各受体亚单位(NR1、NR2A、NR2B)蛋白和m RNA的表达水平。结果与对照组比较,各剂量乙酸铅暴露组仔鼠海马组织中NR1和NR2A蛋白及m RNA的表达水平均较低,除PND 10的0.5 g/L乙酸铅暴露组外,差异有统计学意义(P0.05);且随着乙酸铅暴露剂量的升高,仔鼠海马组织中NR1和NR2A蛋白及m RNA的表达水平呈下降趋势。与对照组比较,PND 10时各剂量乙酸铅暴露组及PND 20时1.0、2.0 g/L乙酸铅暴露组仔鼠海马组织中NR2B蛋白的表达水平均较低,差异有统计学意义(P0.05);而PND 40时各剂量乙酸铅暴露组仔鼠海马组织中NR2B蛋白的表达水平均无明显改变。且随着乙酸铅暴露剂量的升高,PND 10、PND 20时仔鼠海马组织中NR2A蛋白的表达水平均呈下降趋势。各剂量乙酸铅暴露不同发育阶段仔鼠海马组织中NR2B m RNA的表达水平与对照组比较,差异均无统计学意义(P0.05)。结论发育早期铅暴露可损伤仔鼠的学习记忆能力,并且抑制仔鼠海马组织中NMDA受体各亚单位的表达。     

妊娠期MRI静磁场暴露对仔鼠学习记忆能力的影响

[目的]胚胎期脑发育对内外界环境（包括母体环境）的变化极为敏感,本研究旨在探讨妊娠期静磁场暴露对不同月龄仔鼠学习记忆的影响.[方法]将孕鼠置于1.5 T的静磁场中,连续7 d（孕期12～18 d）,每次10 min;将仔鼠根据年龄及性别分为6组：即1、2、5月龄雌性和雄性组;采用Morris水迷宫（Morris Water Maze,MWM）的方法检测各组大鼠的空间学习记忆能力.[结果]与对照组相比,5月龄雌性仔鼠的空间学习与记忆能力均降低,表现为寻找站台的潜伏期明显延长（F=12.609,P＜0.01）,穿越站台次数减少（F=7.680,P＜0.05）;其它各组与对照组相比差异无显著性.[结论]妊娠期静磁场暴露可以降低5月龄雌性仔鼠的空间学习记忆能力.     

铅、锌、镉联合染毒及营养干预致大鼠肝脏病理学变化分析

目的通过动物实验了解铅、锌、镉联合染毒及营养干预对大鼠肝脏病理学变化的影响,为探讨铅锌矿区人群营养干预措施提供理论依据。方法将实验大鼠按照设计分为对照组、染毒组和干预组,分别采用0.01ml/g·bw生理盐水、0.01ml/g·bw铅、锌、镉联合染毒液及119.1mg/kg·bw硫酸亚铁、474mg/kg·bw醋酸钙、14mg/kg·bw核黄素、450mg/kg·bw Vc营养干预液喂饲28d和56d,之后取动物肝脏,用显微镜观察其病理学改变。结果在实验期间,第1、第2阶段染毒组、干预组大鼠体质量增长分别为(32.0±6.3)、(40.9±6.5),(30.3±9.1)、(35.3±7.4)g,分别低于对照组(68.5±8.7)、(46.7±6.3)g,差异有统计学意义(P<0.05)。各组大鼠肝脏系数比较,差异无统计学意义(P>0.05)。对照组大鼠肝脏病理切片无明显改变;染毒组大鼠肝细胞水肿,肝索排列紊乱,肝小叶及汇管区有中性粒细胞及淋巴细胞浸润;干预组大鼠肝细胞水肿不明显,肝小叶及汇管区有少量炎性细胞浸润,可见点状坏死。结论铅、锌、镉联合染毒对大鼠肝脏尚未造成明显的器质性病变,但可能引起肝脏形态功能发生改变,综合营养干预对重金属元素染毒有一定的拮抗作用。     

铅对大鼠海马一氧化氮合酶活力及表达的影响

目的 通过研究铅对大鼠海马一氧化氮合酶（ＮＯＳ）活力及表达的影响。分析海马不同亚区ＮＯＳ活力变化与铅对海马长时程增强（ＬＴＰ）影响的关系。方法 Ｗｉｓｔａｒ大鼠采用饮水加２０、２００、２０００μｇ／ｍｌ醋酸铅（ＰｂＡｃ）方法染毒３个月后,用Ｙ－迷宫法测试大鼠神经行为的改变;用原子吸收法测定血液与海马中铅的含量;用ＮＡＤＰＨ－黄递酶（ＮＡＤＰＨ－ｄ）组化法和免疫组化法检测海马ＮＯＳ的活力及表达情况。