慢性应激对大鼠血压和抑郁行为的影响及治疗探索

The effect of chronic stress on blood pressure and depressive behaviors of rats and therapy exploration

目的探究不可预测慢性温和应激(UCMS)对大鼠血压和抑郁行为的影响及其治疗。方法雄性Wistar-Kyoto(WKY)大鼠15只,自发性高血压大鼠(SHR)15只,分为对照组、UCMS组、UCMS+药物组(n=5)。对照组用生理盐水处理4周;UCMS组,使用7种应激方法共实施21 d;UCMS+药物组,予以UCMS共21 d,及行气活血中成药(冠心丹参滴丸),连续治疗4周。用尾压法测量心率、收缩压(SBP)、舒张压(DBP)、平均动脉压(MAP)。用糖水偏好试验、旷场试验进行行为学检测。用SPSS 24.0统计软件,两组间比较用t检验,多组间比较采用单因素方差分析。结果与WKY对照组比较,WKY大鼠在21d UCMS后DBP[(98.2±13.2)mmHg vs.(56.4±13.8)mmHg,1 mmHg=0.133kPa,P<0.05]、MAP[(103.8±13.2)mmHg vs.(69.2±10.1)mmHg),P<0.05]均明显降低,SHR大鼠的血流动力学指标均无明显变化;与对照组比较,WKY大鼠在UCMS后糖水偏适度明显降低[(79.0±2.3)%vs.(67.5±6.8%)%,P<0.05];WKY大鼠旷场穿行次数显著减少[(50.2±8.5)次vs.(33.4±6.2)次,P<0.05],直立次数亦明显减少[(8.0±1.6)次vs.(4.2±0.8)次,P<0.05];与SHR对照组比较,SHR大鼠在UCMS后糖水饮用量明显降低[(11.0±1.9)g vs.(8.0±1.6)g),P<0.05],纯水饮用量明显增加[(3.0±0.7)g vs.(4.4±1.3)g,P<0.05],糖水偏适度明显降低[(78.4±5.3)%vs.(64.8±6.4%)%,P<0.05];SHR大鼠的旷场穿行次数[(42.0±9.2)次vs.(29.0±6.8)次,P<0.05]、直立次数[(7.4±1.7)次vs.(3.0±0.7)次,P<0.05]均显著减少;与UCMS组比较,SHR大鼠在4周药物治疗后,糖水饮用量明显增加[(8.0±1.6)g vs.(10.5±1.3)g,P<0.05],直立次数显著增加[(3.0±0.7)次vs.(5.0±1.4)次,P<0.05]。结论本研究显示UCMS对SHR大鼠血压没有显著影响,但使WKY大鼠、SHR大鼠均出现抑郁样行为,药物治疗能改善SHR大鼠抑郁样行为。

Objective To explore the effect of unpredictable chronic mild stress(UCMS)on rats'blood pressure and depressive behaviors and the therapeutic method.Methods A total of 15 Wistar-Kyoto(WKY)rats,and 15 spontaneously hypertensive rats(SHR),were respectively divided into three groups,including the control group,UCMS group,and UCMS+treatment group(n=5).The control group was treated with saline for four weeks;the UCMS group was treated with seven kinds of stress for 21 days;the UCMS+treatment group was treated with both UCMS for 21 days and traditional Chinese medicine(Guanxindanshen dropping pills)for four weeks.Tail-cuff was performed to detect heart rate,systolic blood pressure(SBP),diastolic blood pressure(DBP),and mean arterial pressure(MAP).Sucrose preference test and open field test were applied to detect depressive behaviors.SPSS 24.0 was used for statistic analysis,such as student's t-test for two group comparisons and Oneway ANOVA for multiple groups comparisons.Results Compared with the control group,WKY rats with UCMS had a significantly lower level of DBP[(98.2±13.2)mmHg vs.(56.4±13.8)mmHg,1 mmHg=0.133kPa,P<0.05],MAP[(103.8±13.2)mmHg vs.(69.2±10.1)mmHg,P<0.05];While no significant difference of hemodynamic indexes in SHR.Compared with the control group of WKY rats,sucrose preference decreased significantly after UCMS[(79.0±2.3)%vs.(67.5±6.8)%,P<0.05];cross-grid times decreased significantly[(50.2±8.5)times vs.(33.4±6.2)times,P<0.05],stand-up times decreased[(8.0±1.6)times vs.(4.2±0.8)times,P<0.05].Compared with the control group,after UCMS,SHR had fewer sucrose water[(11.0±1.9)g vs.(8.0±1.6)g,P<0.05],higher pure water[(3.0±0.7)g vs.(4.4±1.3)g,P<0.05],lower sucrose water preference[(78.4±5.3)%vs.(64.8±6.4)%,P<0.05];fewer cross-grid times[(42.0±9.2)times vs.(29.0±6.8)times,P<0.05],stand-up times[(7.4±1.7)times vs.(3.0±0.7)times,P<0.05].Compared with UCMS,4-week drug therapy increased sucrose water[(8.0±1.6)g vs.(10.5±1.3)g,P<0.05],and stand-up times(3.0±0.7)times vs.(5.0±1.4)times,P<0.05].Conclusion This study showed that UCMs had no significant effect on the blood pressure of SHR rats but made WKY rats and SHR rats have depression-like behavior.Drug treatment can improve the depression-like behavior of SHR rats.