医药导报
醫藥導報
의약도보
HERALD OF MEDICINE
2015年
4期
435-439
,共5页
孙清%张亮%陈伯成%陈娴%张国琴
孫清%張亮%陳伯成%陳嫻%張國琴
손청%장량%진백성%진한%장국금
丙泊酚%海马%Morris水迷宫%磷酸化tau蛋白%β-淀粉样蛋白
丙泊酚%海馬%Morris水迷宮%燐痠化tau蛋白%β-澱粉樣蛋白
병박분%해마%Morris수미궁%린산화tau단백%β-정분양단백
Propofol%Hippocampus%Morris water maze%Phosphorylated tau protein%Beta-amyloid
目的：探讨怀孕大鼠注射丙泊酚对其后代空间认知探索能力及海马磷酸化tau蛋白( P-tau)、β-淀粉样蛋白(1-42)[ Aβ(1-42)]沉积表达的影响。方法3个月龄24只雌鼠与8只雄鼠按雌雄比3：1合笼受孕。怀孕后按随机数字表法将孕鼠分为早期组(E组)、中期组(M组)、晚期组(L组)和对照组(C组),各6只。 E组、M组、L组经腹腔注射丙泊酚80 mg·kg-1·d-1,连续注射7 d。 C组注射同体积的0.9%氯化钠溶液代替丙泊酚。在孕鼠子代30日龄时进行Morris水迷宫实验,取其海马分别采用免疫组织化学和酶联免疫吸附实验,检测丝氨酸202位点磷酸化 tau 蛋白及Aβ(1-42)表达情况。结果与 C组(65.60±7.23) s相比,E组(51.20±8.11) s、M 组(36.00±6.44) s、L 组(47.20±12.30) s,仔鼠空间学习记忆能力下降,均差异有统计学意义(P<0.05)。免疫组化检测显示M组仔鼠海马Aβ(1-42)和P-tau含量较E组、L组、C组高[Aβ(1-42)：(27.38±5.90)比(12.65±2.08),(13.79±3.37),(65.60±7.23)；P-tau：(26.35±5.83)比(13.65±3.46),(14.56±3.82),(8.49±1.20)]。酶联免疫吸附实验检测亦显示M组仔鼠海马Aβ(1-42)和P-tau含量较E组、L组、C组高[Aβ(1-42)：(88.6±7.43)比(71.60±6.79),(13.79±3.37),(65.80±6.28)；P-tau：(230.13±8.22)比(210.42±2.20),(210.95±1.75),(200.65±1.57)],均差异有统计学差异(P<0.05)。结论孕期多次注射丙泊酚损伤仔鼠空间学习记忆能力,孕中期暴露致损伤最为明显,其机制可能与海马P-tau、Aβ(1-42)沉积过度表达有关。
目的：探討懷孕大鼠註射丙泊酚對其後代空間認知探索能力及海馬燐痠化tau蛋白( P-tau)、β-澱粉樣蛋白(1-42)[ Aβ(1-42)]沉積錶達的影響。方法3箇月齡24隻雌鼠與8隻雄鼠按雌雄比3：1閤籠受孕。懷孕後按隨機數字錶法將孕鼠分為早期組(E組)、中期組(M組)、晚期組(L組)和對照組(C組),各6隻。 E組、M組、L組經腹腔註射丙泊酚80 mg·kg-1·d-1,連續註射7 d。 C組註射同體積的0.9%氯化鈉溶液代替丙泊酚。在孕鼠子代30日齡時進行Morris水迷宮實驗,取其海馬分彆採用免疫組織化學和酶聯免疫吸附實驗,檢測絲氨痠202位點燐痠化 tau 蛋白及Aβ(1-42)錶達情況。結果與 C組(65.60±7.23) s相比,E組(51.20±8.11) s、M 組(36.00±6.44) s、L 組(47.20±12.30) s,仔鼠空間學習記憶能力下降,均差異有統計學意義(P<0.05)。免疫組化檢測顯示M組仔鼠海馬Aβ(1-42)和P-tau含量較E組、L組、C組高[Aβ(1-42)：(27.38±5.90)比(12.65±2.08),(13.79±3.37),(65.60±7.23)；P-tau：(26.35±5.83)比(13.65±3.46),(14.56±3.82),(8.49±1.20)]。酶聯免疫吸附實驗檢測亦顯示M組仔鼠海馬Aβ(1-42)和P-tau含量較E組、L組、C組高[Aβ(1-42)：(88.6±7.43)比(71.60±6.79),(13.79±3.37),(65.80±6.28)；P-tau：(230.13±8.22)比(210.42±2.20),(210.95±1.75),(200.65±1.57)],均差異有統計學差異(P<0.05)。結論孕期多次註射丙泊酚損傷仔鼠空間學習記憶能力,孕中期暴露緻損傷最為明顯,其機製可能與海馬P-tau、Aβ(1-42)沉積過度錶達有關。
목적：탐토부잉대서주사병박분대기후대공간인지탐색능력급해마린산화tau단백( P-tau)、β-정분양단백(1-42)[ Aβ(1-42)]침적표체적영향。방법3개월령24지자서여8지웅서안자웅비3：1합롱수잉。부잉후안수궤수자표법장잉서분위조기조(E조)、중기조(M조)、만기조(L조)화대조조(C조),각6지。 E조、M조、L조경복강주사병박분80 mg·kg-1·d-1,련속주사7 d。 C조주사동체적적0.9%록화납용액대체병박분。재잉서자대30일령시진행Morris수미궁실험,취기해마분별채용면역조직화학화매련면역흡부실험,검측사안산202위점린산화 tau 단백급Aβ(1-42)표체정황。결과여 C조(65.60±7.23) s상비,E조(51.20±8.11) s、M 조(36.00±6.44) s、L 조(47.20±12.30) s,자서공간학습기억능력하강,균차이유통계학의의(P<0.05)。면역조화검측현시M조자서해마Aβ(1-42)화P-tau함량교E조、L조、C조고[Aβ(1-42)：(27.38±5.90)비(12.65±2.08),(13.79±3.37),(65.60±7.23)；P-tau：(26.35±5.83)비(13.65±3.46),(14.56±3.82),(8.49±1.20)]。매련면역흡부실험검측역현시M조자서해마Aβ(1-42)화P-tau함량교E조、L조、C조고[Aβ(1-42)：(88.6±7.43)비(71.60±6.79),(13.79±3.37),(65.80±6.28)；P-tau：(230.13±8.22)비(210.42±2.20),(210.95±1.75),(200.65±1.57)],균차이유통계학차이(P<0.05)。결론잉기다차주사병박분손상자서공간학습기억능력,잉중기폭로치손상최위명현,기궤제가능여해마P-tau、Aβ(1-42)침적과도표체유관。
Objective To study the effects of propofol exposure during pregnancy on space cognitive and exploration abilities and expression of phosphorylated tau protein ( P-tau) and beta-amyloid protein[ Aβ(1-42) ] in hippocampus of the offspring. Methods Sprague-Dawley female (n=24) and male rats (n=8) of three months old were mated at the same cage at the ratio of 3:1. Pregnant rats were randomly divided into early group (group E), medium group (group M), late group (group L) and control group ( group C) , with 6 rats in each group. Groups E, M and L received propofol 80 mg · kg-1 · d-1 for 7 consecutive days. Propofol was replaced with equal volume of physiological saline in group C. Learning and memory of the 30-day offspring rats were assessed by using Morris water maze test. Then offspring rats were sacrificed to determine the expression of P-tau and Aβ(1-42) in the hippocampus by ELISA and immunohistochemistry. Results The learning and memory abilities were declined significantly in group E (51. 20±8. 11) s, group M (36. 00±6. 44) s and group L (47. 20±12. 30) s, as compared with group C (65. 60± 7. 23) s (all P<0. 05). The result of immunohistochemistry and ELISA showed that expression of Aβ(1-42) and P-tau in hippocampus was significantly higher in group M than in groups E, L and C[(immunohistochemistry: Aβ(1-42), (27. 38±5. 90) vs. (12. 65± 2. 08), (13. 79±3. 37), and (65. 60±7. 23); P-tau, (26. 35±5. 83) vs. (13. 65±3. 46), (14. 56±3. 82), and (8. 49±1. 20);ELISA:Aβ(1-42) , (88. 6±7. 43) vs. (71. 60±6. 79), (13. 79±3. 37), and (65. 80±6. 28);P-tau, (230. 13±8. 22) vs. (210. 42± 2.20), (210.95±1. 75), and (200. 65±1. 57)] (all P<0.05). Conclusion Multiple propofol injections may impair rat offspring’ s space cognitive abilities and exploration abilities, and the impairment is especially obvious in second trimester of pregnancy, which may be associated with over-expression of P-tau and Aβ(1-42) .
