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) .%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。
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