丹参多酚酸对慢性应激大鼠抑郁相关行为改善的研究

The effects of salvianolic acid on depression related behavior in chronic mild stress rats

目的 观察丹参多酚酸对慢性温和应激抑郁模型大鼠抑郁行为的影响.方法 将33只健康雄性,体质量150～200 g的清洁级Sprague Dawley （SD）大鼠按随机数字表法分为5组,分别为非应激＋生理盐水组（对照组,6只）,应激＋生理盐水组（生理盐水组,6只）,应激＋氟西汀组（氟西汀组,7只）,应激＋丹参多酚酸组（丹酚酸组,7只）,应激＋氟西汀＋丹酚酸组（联合组,7只）.除对照组外,其他4组连续21d进行慢性温和应激造模.造模成功后,每天下午各组分别腹腔注射相对应的0.9％氯化钠10 ml/kg,氟西汀20 mg/kg,丹参多酚酸40 mg/kg,丹酚酸40 mg/kg＋氟西汀20 mg/kg,体积体质量比10 ml/kg,每周进行蔗糖偏好试验,称重,给药21d后进行旷场试验、强迫游泳测试以评价药物对大鼠抑郁样行为的作用.对基线水平体质量（g）、应激21d后与给药21d后体质量、蔗糖偏好率（％）、强迫游泳后4 min静止不动时间（s）、旷场探究活动（爬格个数、站立次数、修饰次数及粪便粒数）进行单因素方差分析和LSD法两两比较.结果 （1）应激21d后,5组大鼠体质量、蔗糖偏好率、强迫游泳静止不动时间、旷场试验中爬格个数和站立次数的差异有统计学意义（F分别为3.747,14.968,8.439,38.925,7.893,均P＜0.05）,应激的4组大鼠体质量、蔗糖偏好率、爬格个数、站立次数均低于对照组,静止不动时间高于对照组,差异有统计学意义（均P＜0.05）.两两比较结果显示,应激的4组大鼠均值低于对照组（均P＜0.01）,但4组间差异无统计学意义.（2）给药21d后,5组大鼠的体质量、蔗糖偏好率、强迫游泳静止不动时间、旷场试验中站立次数和爬格数差异有统计学意义（F分别为8.179,6.609,27.608,34.149,4.341,均P＜0.01）,氟西汀组、丹酚酸组、联合组及对照组体质量、蔗糖偏好率均高于生理盐水组（均P＜0.05）,静止不动时间低于生理盐水组（P均＜0.05）,但4组间两两比较体质量、蔗糖偏好率、不动时间的差异无统计学意义.旷场试验中氟西汀组、丹酚酸组、联合组的站立次数均值高于对照组和生理盐水组（均P＜0.01）,而3组间站立次数差异无统计学意义.结论 丹参多酚酸能改善大鼠抑郁相关行为,疗效与氟西汀相当.

Objective To observe the effect of salvianolic acid on the depressive behavior in rats.Methods 33 healthy male Sprague Dawley （SD） rats were divided into 5 groups,one control group with no stress challenge（n=6） and 4 chronic stress groups（saline group,n=6;fluoxetine group,n=7;salvianolic acid group,n=7;fluoxetine ＋ salvianolic acid combination group,n=7.The rats but not in control group were exposed to stress for 3 weeks,and then were daily afternoon injected intraperitoneally saline（10 ml/kg）,fluoxetine（20 mg/kg）,salvianolic acid（40 mg/kg） or combined fluoxetine and salvianolic acid,with dosage of 10 ml/kg.Sucrose preference test and the weights of rats were measured every week.Open field test （OFT）and forced swimming test （FST） were performed after chronic stress challenge and drug treatment to assess the effect of drug treatments on depressive-like symptoms.One-way ANOVA and LSD methods were adopted to compare two groups （the weight （g） of rats,the last 4 minutes duration of immobility in the forced swimming test （s）,sucrose preference values（％） and open field locomotor activities （the number of crossing grids,stand-up times,grooming times and feces） of the baseline,21days after stress exposure and 21 days after drug injection）.Results 21 days after stress exposure,differences were found in the body weights,sucrose preference values,the last 4 minutes duration of immobility in the forced swimming test and the locomotor activities for 5 minutes （the number of crossing grids and stand-up times） in the OFf （F were 3.747,14.968,8.439,38.925,7.893 respectively,all had P＜0.05）.The weights,sucrose preference values and the locomotor activities in the OFf of the 4 stress groups were lower than control group,yet the last 4minutes duration of immobility in the forced swimming test were higher than control group （all P＜0.05）.According to LSD test,the mean of the above data in the 4 stress groups were lower than control group respectively （all P＜0.01）,but no significant difference in the 4 stress groups （all P＞0.05）.21days after drug were given,differences were found in the weights of 5 groups,sucrose preference values,the last 4 minutes duration of immobility in the forced swimming test as well as the number of crossing grids and stand-up times in the OFT （F were 8.179,6.609,27.608,34.149,4.341 respectively,all P＜0.01）.Body weights of the fluoxetine,salvianolic acid,combination,control groups were higher than saline group （all P＜0.05）,yet the duration of immobility of which groups were lower than saline group （all P＜0.05）.Otherwise,no difference of the weights,sucrose preference values and the duration of immobility were found in these 4 groups as compared in pairs （all P＞0.05）.The number of stand-up times in the fluoxetine,salvianolic acid and combination groups were higher than the control and saline groups as compared in pairs （all P＜0.01）,except that,no differences of the number of standings were found in the fluoxetine,salvianolic acid and combination groups （all P＞0.05）.Conclusion Salvianolic acid could improve the behaviors of rat with depression,and the effect of which may be comparable to fluoxetine.