中国地方病学杂志
中國地方病學雜誌
중국지방병학잡지
CHINESE JOURNAL OF ENDEMIOLOGY
2011年
3期
251-255
,共5页
刘艳洁%高勤%龙义国%于燕妮%官志忠
劉豔潔%高勤%龍義國%于燕妮%官誌忠
류염길%고근%룡의국%우연니%관지충
氟化物中毒%脑%转录因子Elk-1%学习%记忆
氟化物中毒%腦%轉錄因子Elk-1%學習%記憶
불화물중독%뇌%전록인자Elk-1%학습%기억
Fluoride poisoning%Brain%Transcription factor Elk-1%Learning%Memory
目的 观察慢性氟中毒大鼠脑组织中细胞外调节蛋白激酶(ERK1/2)信号转导通路下游作用底物三元复合物因子Phospho-Elk-1的表达和分布,探讨慢性氟中毒所致学习记忆损害的发生机制.方法 SD 大鼠72只,体质量100～120 g,按体质量随机分为3组,每组24只,雌雄各半.对照组饮用自来水(含氟量<0.5 mg/L),低氟组和高氟组饮用加入氟化钠的自来水(P质量浓度分别为5.0、50.0 mg/L).6个月后,称取大鼠体质量,观察氟斑牙发生情况,用氟离子选择电极法检测大鼠尿氟及骨氟;用Morris水迷宫方法的定向航行实验检测大鼠学习能力,空间探索实验检测大鼠记忆能力;用免疫组织化学方法检测大鼠脑组织中Phospho-Elk-1在蛋白水平的表达和分布.结果 低氟组和高氟组大鼠体质量[(449.2±77.1)、(312.8 ±89.7)g]较对照组[(635.5±76.2)g]显著下降(P均<0.05),出现不同程度氟斑牙(x2=7.83,P<0.05),尿氟[(2.56±0.91)、(5.73±3.14)mg/L]及骨氟[(709.2±37.4)、(1306.3 ±102.4)mg/kg]较对照组[(0.92±0.30)mg/L、(348.5 ±89.2)mg/kg]明显升高(P均<0.05).低氟组和高氟组大鼠逃避潜伏期[(7.4±4.1)、(12.2±5.7)s]较对照组[(4.8±2.7)s]明显延长(P均<0.05),第1次穿越平台区时同[(4.18±1.10)、(5.89±0.56)s]较对照组[(1.17±0.75)s]显著延长(P均<0.05),均以高氟组尤为明显(P均<0.05).低氟组和高氟组大鼠海马CA1区(167.4±8.3、163.2±9.4)、CA2区(175.7±5.0、183.3±4.2)、CA3区(165.2±11.6、162.9±4.4)、CA4 区(168.7±6.9、169.5±5.3)、齿状回(185.2 ±4.0、193.1±6.1)及尾壳核(181.4±3.8、179.8±5.5)神经细胞Phospho-Elk-1表达水平较对照组(142.4±8.1、144.9±8.4、143.6±5.8、116.8±9.1、140.2±7.8、163.1±13.1)显著增加(P均<0.05).结论 慢性氟中毒可引起大鼠脑组织海马及尾壳核区域Pbospho-Elk-1表达水平升高,这种改变可能与大鼠学习记忆能力下降机制有一定关系.
目的 觀察慢性氟中毒大鼠腦組織中細胞外調節蛋白激酶(ERK1/2)信號轉導通路下遊作用底物三元複閤物因子Phospho-Elk-1的錶達和分佈,探討慢性氟中毒所緻學習記憶損害的髮生機製.方法 SD 大鼠72隻,體質量100～120 g,按體質量隨機分為3組,每組24隻,雌雄各半.對照組飲用自來水(含氟量<0.5 mg/L),低氟組和高氟組飲用加入氟化鈉的自來水(P質量濃度分彆為5.0、50.0 mg/L).6箇月後,稱取大鼠體質量,觀察氟斑牙髮生情況,用氟離子選擇電極法檢測大鼠尿氟及骨氟;用Morris水迷宮方法的定嚮航行實驗檢測大鼠學習能力,空間探索實驗檢測大鼠記憶能力;用免疫組織化學方法檢測大鼠腦組織中Phospho-Elk-1在蛋白水平的錶達和分佈.結果 低氟組和高氟組大鼠體質量[(449.2±77.1)、(312.8 ±89.7)g]較對照組[(635.5±76.2)g]顯著下降(P均<0.05),齣現不同程度氟斑牙(x2=7.83,P<0.05),尿氟[(2.56±0.91)、(5.73±3.14)mg/L]及骨氟[(709.2±37.4)、(1306.3 ±102.4)mg/kg]較對照組[(0.92±0.30)mg/L、(348.5 ±89.2)mg/kg]明顯升高(P均<0.05).低氟組和高氟組大鼠逃避潛伏期[(7.4±4.1)、(12.2±5.7)s]較對照組[(4.8±2.7)s]明顯延長(P均<0.05),第1次穿越平檯區時同[(4.18±1.10)、(5.89±0.56)s]較對照組[(1.17±0.75)s]顯著延長(P均<0.05),均以高氟組尤為明顯(P均<0.05).低氟組和高氟組大鼠海馬CA1區(167.4±8.3、163.2±9.4)、CA2區(175.7±5.0、183.3±4.2)、CA3區(165.2±11.6、162.9±4.4)、CA4 區(168.7±6.9、169.5±5.3)、齒狀迴(185.2 ±4.0、193.1±6.1)及尾殼覈(181.4±3.8、179.8±5.5)神經細胞Phospho-Elk-1錶達水平較對照組(142.4±8.1、144.9±8.4、143.6±5.8、116.8±9.1、140.2±7.8、163.1±13.1)顯著增加(P均<0.05).結論 慢性氟中毒可引起大鼠腦組織海馬及尾殼覈區域Pbospho-Elk-1錶達水平升高,這種改變可能與大鼠學習記憶能力下降機製有一定關繫.
목적 관찰만성불중독대서뇌조직중세포외조절단백격매(ERK1/2)신호전도통로하유작용저물삼원복합물인자Phospho-Elk-1적표체화분포,탐토만성불중독소치학습기억손해적발생궤제.방법 SD 대서72지,체질량100～120 g,안체질량수궤분위3조,매조24지,자웅각반.대조조음용자래수(함불량<0.5 mg/L),저불조화고불조음용가입불화납적자래수(P질량농도분별위5.0、50.0 mg/L).6개월후,칭취대서체질량,관찰불반아발생정황,용불리자선택전겁법검측대서뇨불급골불;용Morris수미궁방법적정향항행실험검측대서학습능력,공간탐색실험검측대서기억능력;용면역조직화학방법검측대서뇌조직중Phospho-Elk-1재단백수평적표체화분포.결과 저불조화고불조대서체질량[(449.2±77.1)、(312.8 ±89.7)g]교대조조[(635.5±76.2)g]현저하강(P균<0.05),출현불동정도불반아(x2=7.83,P<0.05),뇨불[(2.56±0.91)、(5.73±3.14)mg/L]급골불[(709.2±37.4)、(1306.3 ±102.4)mg/kg]교대조조[(0.92±0.30)mg/L、(348.5 ±89.2)mg/kg]명현승고(P균<0.05).저불조화고불조대서도피잠복기[(7.4±4.1)、(12.2±5.7)s]교대조조[(4.8±2.7)s]명현연장(P균<0.05),제1차천월평태구시동[(4.18±1.10)、(5.89±0.56)s]교대조조[(1.17±0.75)s]현저연장(P균<0.05),균이고불조우위명현(P균<0.05).저불조화고불조대서해마CA1구(167.4±8.3、163.2±9.4)、CA2구(175.7±5.0、183.3±4.2)、CA3구(165.2±11.6、162.9±4.4)、CA4 구(168.7±6.9、169.5±5.3)、치상회(185.2 ±4.0、193.1±6.1)급미각핵(181.4±3.8、179.8±5.5)신경세포Phospho-Elk-1표체수평교대조조(142.4±8.1、144.9±8.4、143.6±5.8、116.8±9.1、140.2±7.8、163.1±13.1)현저증가(P균<0.05).결론 만성불중독가인기대서뇌조직해마급미각핵구역Pbospho-Elk-1표체수평승고,저충개변가능여대서학습기억능력하강궤제유일정관계.
Objective To investigate the expression and distribution of the downstream substrate of extracellular regulated protein kinase(ERK1/2) pathway, ternary complex factor phospho-Elk-1, in rat brains with chronic fluorosis, and reveal the mechanism of the impaired learning and memory ability caused by chronic fluorosis. Methods Seventy-two SD rats, weighing 100 - 120 g, were randomly divided into 3 groups, 24 in each group (half male and half female). The rats in control group were fed with tap water (fluoride < 0.5 mg/L); low- and high-dose fluoride groups were fed with tap water with different concentrations of NaF(5.0,50.0 mg/L F-, respectively). After 6 months, body weight was weighed, dental fluorosis was determined by observation and urinary fluoride and bone fluoride were detected by fluorine ion-selective electrode; the learning ability of rats was measured by navigation test of Morris water maze, and memory ability by spatial probe test in Morris water maze; the expression and distribution of phospho-Elk-1 in different brain regions were detected by immunohistochemistry method. Results In low- and high-fluoride groups, the body weight of rat[(449.2 ± 77.1), (312.8 ± 89.7)g] was significantly decreased than that of control [(635.5 ± 76.2 )g, all P< 0.05], the varying degrees of dental fluorosis were observed(x2 = 7.83, P<0.05), urinary fluoride[(2.56 ±0.91),(5.73 ±3.14)mg/L] and bone fluoride[(709.2 ± 37.4) ,(1306.3 ± 102.4) mg/kg] were significantly higher than those in controls[(0.92 ± 0.30)mg/L,(348.5 ± 89.2)mg/kg, all P< 0.05]. The escape latency of low- and high-fluoride groups[ (7.4 ± 4.1), (12.2 ± 5.7)s] was longer than that of control [(4.8 ± 2.7 )s, all P < 0.05] and the escape latency in high-fluoride group was significantly longer than that in other groups (all P < 0.05); in spatial probe test, the time of first crossing platform was longer in rats with fluorosis [(4.18 ± 1.10),(5.89 ± 0.56)s] as compared to control[(1.17 ± 0.75)s, all P< 0.05]. Expressions of phospho-Elk-1 in the hippocampus CA1(167.4 ± 8.3,163.2 ± 9.4), CA2(175.7 ± 5.0,183.3 ± 4.2), CA3(165.2 ± 11.6,162.9 ± 4.4), CA4(168.7± 6.9,169.5 ±5.3), fascia dentate (185.2 ±4.0,193.1 ±6.1) and caudate putamen( 181.4 ± 3.8, 179.8 ± 5.5) in low- and high-fluoride groups were higher than those of controls(142.4 ± 8.1,144.9 ± 8.4,143.6 ± 5.8, 116.8 ± 9.1,140.2 ± 7.8,163.1 ± 13.1, all P< 0.05). Conclusion Chronic fluorosis can cause increased expression of phospho-Elk-1 in the hippocampus and caudate putamen region of rat brains, which might be related to the mechanisms of decreased learning and memory ability of rats overexposed to fluoride.
