妊娠期L-NAME干预对子代大鼠学习认知能力的影响

The Nitric Oxide Synthesis Inhibitor NW-Nitro-L-Arginie Methyl Ester（L-NAME） Causes Cognitive Ability Impairment in Offspring Rats

目的探讨妊娠期亚硝基左旋精氨酸甲酯（L-NAME）干预对子代大鼠学习认知能力的影响。方法通过给妊娠13d大鼠连续7d皮下注射L-NAME的方法建立妊娠期高血压疾病的大鼠模型，并根据剂量不同分为高剂量纽（每天125mg／kg）及低剂量纽（每天75mg／kg），对照纽予生理盐水1ml皮下注射。待自然分娩后，子代大鼠喂养至8周龄进行Morris水迷宫实验，分为定向导航试验研究智力和学习能力，空间探索试验研究记忆和空间定位能力。结果在妊娠期高血压疾病模型中，水迷宫定向导航试验第1天，高剂量组和低剂量组的逃避潜伏期（72．45±26．98S，71．25±27．61s）均明显长于对照组（56．07±20．30s）（P〈0．05）；训练第4天，高剂量组逃避潜伏期（31．91±24．96s）显著高于对照组（21．17±19．47s）（P〈0．05）。在空间探索试验中，低剂量组子代大鼠在站台所在的Ⅳ象限路程百分比（26．65％±10．63％）显著低于对照组（33．73％±13．98％）（P〈0．05）。结论妊娠期L-NAME干预导致子代大鼠的智力受损，学习能力无明显差异。记忆和空间定位能力也有所降。

Objective To explore the relationship between exposure to the nitric oxide synthesis inhibitor N^ω-nitro-L-arginine methyl ester （L-NAME） and the impairment of cognitive ability in offspring rats. Methods Maternal rats are randomly divided into 3 groups： （1） high dose group： maternal rats are subcutaneously injected with 125 mg/kg L-NAME in the 13th gestational day, and persisting in 7 days;（2） low dose group： maternal rats are subcutaneously injected with 75mg/kg L-NAME in the 13th gestational day, and persisting in 7 days;（3） control group： maternal rats are subcutaneously injected with 1 ml of 0.9% NaC1 in the 13th gestational day, and persisting in 7 days. After the maternal rats is spontaneous delivery, the offspring rats are fed till they are 8 weeks old. The offspring rats were tested for visual-spatial learning and memory and spatial localization abilities in Morris water maze. Results In the animal model of preeclampsia, in the 1 st day of place navigation test, the escape latent period of high dose group and low dose group is significant longer than that of control group （P〈0.05）. In the 4th day, the escape latent period of high dose group is significant longer than that of control group （P〈0.05）. In spatial exploration test, the percent of IV quadrant distance of low dose group is significant lower than that of control group（P〈0.05）. Conclusion Exposure to the L-NAME results in the impairment of intelligence of the offspring rats. The study pattern has not significant difference. And the memory and space direction ability of offspring rats is impaired.