宫内注射内毒素对早产子代大鼠学习记忆能力影响的研究

Study on the effect of lipopolysaccharide intrauterine injection on the learning and memory ability of the preterm rat offspring

目的探讨内毒素(LPS)宫内注射构建大鼠早产模型的有效性及其对早产仔鼠学习记忆能力的影响,为后期研究奠定基础。方法建造SD孕鼠宫内感染早产模型,30只孕鼠随机分为两组(实验组和对照组),两组于孕17日分别宫内注射100μl 25%LPS溶液或100μl生理盐水,观察妊娠结局;仔鼠于生后1月进行Morris水迷宫的定位航行实验及空间探索实验,检测子代空间学习记忆能力的改变。结果实验组早产率(100%)和死产率(2.9%)均显著高于对照组(6.7%和0.9%)(χ~2分别为11.46,8.82,P<0.05);平均每窝活产仔鼠数(t=4.83,P=0.02)、仔鼠平均体重(t=3.75,P=0.03)、1月仔鼠存活率(χ~2=3.68,P=0.03)均显著低于对照组。在水迷宫任务中实验组更多采取非有效策略,对照组更多地采取有效策略,两组间差异有统计学意义(χ~2=4.27,P=0.02)。实验组1月龄仔鼠的平均潜伏期较对照组明显延长(t=6.92,P=0.001)。空间探索实验中,实验组1月龄仔鼠站台停留时间较对照组明显缩短(t=5.28,P=0.005)。结论宫内LPS注射法是一种可行性较高、成功率较高的造模方法,该方法所致早产仔鼠学习记忆能力受损,可用于宫内炎症所致早产的相关研究。

Objective To discuss the effectiveness of lipopolysaccharide(LPS) intrauterine injection for establishing a premature rat model and the changes of learning and memory ability of the preterm birth pups. Methods A preterm birth model induced by intrauterine immflammation of SD pregnant rats was established.Thirty pregnant rats were randomly divided into experimental group and control group,with 15 rats in each group.All rats of the two groups were intrauterinely injected with 100 μl 25%LPS solution or 100 μl physiological saline on the 17 th day of pregnancy,then the pregnancy outcome was observed.Navigation experiment and space exploration experiment of morris water maze were conducted in the first month after birth to test the changes of ability on the spatial learning and memory of the offspring. Results The preterm birth rate and stillbirth rate of the experimental group were significantly higher than those of control group(preterm birth:100% vs.6.7%,χ^2=11.46,P<0.05;stillbirth:2.9% vs.0.9%,χ^2=8.82,P<0.05).The average number of per litter(t=4.83,P=0.02),the average weight of offspring(t=3.75,P=0.03) and the survival rate of offspring in the first month after birth(χ^2=3.68,P=0.03) in experimental group were significantly lower than those in control group.In the Morris water maze task,the experimental group adopted more non-effective strategies,while the control group adopted more effective strategies,and the difference was significant(χ^2=4.27,P=0.02).The average incubation period of one-month-old rats in the experimental group was significantly longer than that in the control group(t=6.92,P=0.001).While the station stay time of one-month-old pups of experimental group was significantly shorter than that of the control group in space exploration experiment(t=5.28,P=0.005). Conclusions LPS intrauterine injection is a modeling method with high feasibility and success rate,which will result in impaired learning and memory ability of early litter rats.So it can be used in the related studies on premature labor caused by intrauterine inflammation.