| Objective: To observe the effect of salvianolic acid on depressive-like behaviors of rats induced by chronic mild stress,and the changes of relative telomere length in the whole blood and right hippocampus after stress.Methods: 92 healthy and clean male Sprague Dawley(SD)rats,weight in 110-150 g,were randomly divided into five groups: non stress+ saline group(control group),n=19;stress+saline group,n=19;stress+ fluoxetine group(fluoxetine group),n=18;stress+salvianolic acid group(salvianolic acid group),n=20;stress fluoxetine+salvianolic acid group(combination group),n=16.Two kinds of stress methods were given to rats except control group,the same stress cannot occur continuously,average of each stimulus was used 3 times,so that the animal couldn't predict the occurrence of stress.The control group did not receive any experimental stressor.Depression model was established after 3 weeks' stress.The above stress was continued every day,and the groups were give an intraperitoneal injection with salvianolic acid 40 mg/kg,fluoxetine 20 mg/kg,0.9% sodium chloride,combination of salvianolic acid 40 mg/kg and fluoxetine 20 mg/kg respectively,its volume weight ratio was 10 ml/kg.Sucrose preference test was adopted weekly,recording the sucrose and water consumption of the rats.Calculated sucrose preference rate(G,%),sucrose preference rate=(sucrose consumption/(sucrose consumption+ water consumption)×100%.Weight and its growth rate(K,%)were recorded,namely,the weight growth rate after 3 weeks' stress =(the weight after 3 weeks' stress-the baseline of weight)/ the weight after 3 weeks' stress×100%;the weight growth rate of 3 weeks' drug injection =(the weight growth rate of 3 weeks 'drug injection-the weight after 3 weeks' stress)/ the weight growth rate of 3 weeks' drug injection×100%.Forced swimming test,Morris water maze test(MWM)were adopted after 3 weeks' stress and drug injection.SPSS19.0 was used to analyze data.Weight of rats(unit: g),sucrose preference rate(G,unit: %),T4,the mean of average escape latency of rats in the first 5 days,the mean of rats across to platform quadrant in the sixth day in Morris Water Maze and the relative telomere length of the whole blood in rats after 3 weeks' drug injection were recorded as mean± standard deviation(sx ?),yet the relative telomere length of right hippocampus in rats after 3 weeks' drug injection was recorded as Median(Interquartile range),namely M(IQR).Significant level was P<0.05.The baseline of weight,the growth rate of weight,sucrose preference rate,the total stationary time of the last 4 minutes of rats in the forced swimming test(T4,unit: s)and the time of rats across to platform quadrant in the sixth day in Morris Water Maze variables were analyzed by one-way ANOVA,Bonferroni test was analyzed for group comparison.Repeated measures analysis was adopted for the mean of average escape latency of rats in the first 5 days in the MWM.Paired samples t test was used for analyzing the time of rats across to platform quadrant in the sixth day in MWM before and after drug administration.Relative telomere length on the right hippocampus of rats was adopted with Kruskal Wallis-H test,Nemenyi test was used for comparison between two groups.Result:1 In the baseline,weight difference and sucrose preference rate in 5 groups were no statistically significant(F=1.412,P=0.237;F=2.175,P=0.078).2 Depression rat model was established successfully.Differences were found in 5 groups of K after 3 weeks' stress(F=10.775,P<0.001).There was statistical difference in the K(all P<0.001)when the combination group,fluoxetine group,salvianolic acid group compared with control group respectively.And statistical difference of G was also existed in 5 groups(F=12.453,P < 0.001),saline group:(43.95±12.38)%,fluoxetine group:(48.56±12.25)%,salvianolic acid group:(48.00±10.33)%,combination group:(45.31±10.17)%,control group:(67.37±13.02)%.Among them,G of control group was higher than other stress groups(all P<0.001).Except that,there was statistical difference of T4 in the 5 groups(F=4.777,P=0.002),saline group:(32.55±10.54)s,fluoxetine group:(31.93±13.99)s,salvianolic acid group(34.72±10.66)s,combination group:(35.02±12.75)s,control group:(18.68±5.28)s.T4 of each stress group was higher than control group(all P<0.05).There was significant difference in the mean of average escape latency of 5 groups' rats in the first 5 days of MWM(F=5.732,P<0.001),and difference was found in the measurements of the time(F=136.000,P< 0.001).Yet there was no significant difference between the treatment groups and measurements in the different time(F=1.964,P=0.061).Multivariate analysis of variance showed that no statistical significance was found between every two groups on the first day after the stress(F=0.272,P>0.05),there was no significant difference in the average escape latency of each group rats after the 2-5 days of stress(F were 15.148,6.632,2.009,2.743 respectively,all P<0.05).According to Bonferroni test,the mean of average escape latency of stress groups in the 2nd day of the MWM were higher than that in control groups(all P<0.05),yet no difference of that was found in the stress groups(all P>0.05).The significant difference of mean time of rats across to platform quadrant was existed in the 6th day of MWM by one-way ANOVA(F=19.233,P<0.001).The time of 4 stress groups' rats across to platform quadrant were lower than control group(all P<0.001),and there was no significant difference between stress groups(all P>0.05).3 Significant difference of K was found in the 5 groups after 3 weeks' drug injection(F=10.084,P<0.001),saline group:(11.17±4.65)%,fluoxetine group:(22.34±6.70)%,salvianolic acid group:(19.11±4.76)%,combination group:(21.08±7.25)%,control group:(19.67±6.67)%.Yet no difference of K was found when comparing fluoxetine group with salvianolic acid group and combination group respectively(all P>0.05).The K in fluoxetine group was higher than saline group(P<0.001);There was no statistically difference when comparing salvianolic acid group with combination group and control group respectively(all P>0.05).K in salvianolic acid group was higher than saline group(P=0.001),yet no difference of K was found when comparing salvianolic acid group with combination group(P>0.05).There was obvious difference of K was found between saline group and combination group(P<0.001).Otherwise,Significant difference of G was found in 5 groups after 3 weeks' drug injection(F=6.609,P<0.001).There was no difference of G when comparing fluoxetine,salvianolic acid and combination groups with control group respectively(all P>0.05).The G in saline group was lower than other groups(P<0.001).Moreover,the difference of T4 was found in 5 groups after 3 weeks' drug injection(F=6.137,P<0.001),and no difference was found when the T4 of fluoxetine,salvianolic acid and combination groups comparing with control group respectively(all P>0.05).And no differences was found in T4 when fluoxetine group was compared with salvianolic acid group and control group respectively(all P > 0.05).In MWM test,the difference of average avoid latency was existed in the five groups in the first 5 days(F=16.243,P<0.001).Similarly,there was significant difference in measure time(F=9.359,P<0.001).Multivariate analysis of variance showed that statistical significance were found between every two groups on the first 5 days after drug injection(F were 6.762,7.248,3.923,8.145,4.678 respectively,all P<0.05).When combination group,fluoxetine group and combination group were compared with control group respectively by Bonferroni test,no difference of average avoid latency was found in the first day of the MWM(all P>0.05),yet there was a difference of average avoid latency was found between control group and saline group(both P<0.05).Except that,saline group was higher than other groups in average avoid latency(all P<0.001).And a significant difference was found in crossing the platform quadrant in the 6th day of MWM(F=14.499,P < 0.001).By Bonferroni test,no difference was found when comparing control group with fluoxetine group,saline group and combination group respectively(all P>0.05).The time of crossing platform quadrant of rats was lower than other groups(all P<0.05),yet time of crossing platform quadrant in combination group was higer than salvianolic acid group(P<0.05).After 3 weeks' drug injection,there was statistical significance difference in the relative telomere length of the whole blood of 5 groups(F=18.910,P<0.001).The relative telomere length of the whole blood length in the group of fluoxetine,salvianolic acid,combination was higher than saline group by Bonferroni test(P<0.001).The relative telomere length of right hippocampus in rats analyzed by Kruskal Wallis-H test(?2=12.004,P<0.05).The mean relative telomere length of the right hippocampus in the groups of control,fluoxetine,salvianolic acid and combination,which was higher than saline group by Nemenyi test(all P<0.05).Conclusions:1 3 weeks' chronic mild stress led to rats' depression like behavior.2 The relative telomere length of right hippocampus and whole blood of depressed saline group rats were decreased.3 Both salvianolic acid and fluoxetine therapy could improve the depression like behaviors in rats.4 Salvianolic acid could improve cognitive function in depression rats,with antidepressants fluoxetine the treatment effect may be superior to use salvianolic acid alone.5 The drug of salvianolic acid,fluoxetine may affect the telomere length. |
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