法舒地尔对慢性不可预见性温和应激所致大鼠抑郁样行为和海马区神经形态学的影响

Effects of Fasudil on depressive⁃like behavior and neuromorphology of the hippocampus in rats with chronic unexpected mild stress

目的:观察法舒地尔干预对慢性不可预见性温和应激(CUMS)所致大鼠抑郁样行为和海马区神经形态学的影响。方法:选取5周龄雌性SD大鼠30只,采用CUMS构建大鼠抑郁模型,随机分为3组,每组10只。对照组每天抓取1次,共计22 d;CUMS模型组每天给予1种应激刺激,共计22 d,在CUMS前4 d开始,每天腹部注射生理盐水0.2 mL;法舒地尔干预组在CUMS前4 d开始,每天腹腔注射,并予以30 mg/kg法舒地尔干预。以糖水偏好实验、旷场实验、Morris水迷宫测试大鼠抑郁样行为。HE染色观察海马区病理形态变化。结果:CUMS模型组较对照组大鼠的糖水消耗量、糖水偏好率下降,中央格活动时间、站立次数和修饰行为减少(P<0.05),逃避潜伏期和行走总路程延长(P<0.05);法舒地尔预处理能够改善CUMS诱导的抑郁样行为,差异均有统计学意义(P<0.05)。HE染色结果显示,CUMS组海马神经细胞排列不齐、疏松,锥体细胞层数变少,细胞收缩,突起减少,法舒地尔干预组较CUMS模型组病变程度减轻。结论:CUMS大鼠出现抑郁样行为,法舒地尔能够改善CUMS所致大鼠的抑郁样行为,CUMS所致的海马神经结构异常可能是其抑郁样行为的重要病理学基础之一。

Objective:To observe the effects of Fasudil intervention on depression⁃like behavior and neuromorphology of hippocampus in rats induced by chronic unexpected mild stress(CUMS).Methods:Totally 30 Sprague Dawly(SD)rats at 5 week old were recruite,the depression mudels were established using CUMS and then randomly divided into control group,CUMS model group,and Fasudil intervention group,with 10 rats in each group.CUMS was used to construct a rat depression model,and 30 mg/kg Fasudil was intervened.The depression⁃like behaviors of rats were tested by sugar water preference test,open field test,and Morris water maze.Hematoxy lineosin(HE)staining was used to observe the pathological changes in the hippocampus.Results:Compared with the control group,the sugar water consumption and the percentage of sugar water preference in the CUMS model group decreased;the central grid activity time,standing times,and modification behaviors reduced(P<0.05);the escape latency and total walking distance prolonged(P<0.05);Fasudil pretreatment could improve depression⁃like behaviors induced by CUMS,and the differences were statistically significant(P<0.05).The results of HE staining showed that the hippocampal nerve cells in the CUMS group were unevenly arranged and loose,the number of pyramidal cells decreased,the cells contracted,and the protrusions decreased.The Fasudil intervention group had less degree of pathologic change than the model group.Conclusions:CUMS rats had depression⁃like behaviors.Fasudil could improve the depression-like behaviors of CUMS rats.The abnormal structure of the hippocampus caused by CUMS might be one of the important pathological bases of their depression⁃like behaviors.