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大鼠恐惧应激模型中行为与心血管指标变化

发布时间:2018-09-10 08:59
【摘要】:目的:建立条件恐惧应激致大鼠心血管损伤防治药物药效评价实验动物模型,观察恐惧应激对大鼠心血管功能的损伤效应,并对心血管损伤相关备选指标进行综合的检测、分析、评价。筛选有意义的评价抗恐惧药物药效备选指标,以备今后建立评价体系使用。 方法: 64只健康雄性wistar大鼠随机分为恐惧模型组与对照组,每组32只。自由摄食饮水饲养10天后,第11天起恐惧模型组每日给予2s噪音+3s足底电流刺激,电流强度为1mA,间隔1min,共30次,第12、13天重复实验;对照组每日只给予2s噪音,无足底电流刺激,间隔1min,共30次,第12、13天重复实验。第14天摄像记录两组大鼠5min噪音之后第6—30min内行为变化,评定造模是否成功。自造模成功之后第二日算起分别于1、2、3、4周每周周中(第18、25、32、39天),对两组大鼠进行体重、自发活动、血压心率以及大鼠血清高敏C反应蛋白、肌酸激酶同工酶、心肌钙蛋白I含量测定。 结果: (1)第14天摄像观察两组大鼠5min噪音之后行为学反应,采用三人评定法,恐惧模型组冻结时间显著高于对照组,差异有统计学意义(P0.05),证明造模成功。(2)两组大鼠体重均称自然增长态势,第1周两组大鼠体重无显著性差异,第2周(P0.05)、3周(P0.05)、4周(P0.01)两组大鼠体重比较均差异显著。(3)两组大鼠自发活动比较,恐惧模型组活动次数在第1周(P0.05)、2周(P0.01)、3周(P0.01)、4周(P0.05)均显著少于对照组,差异显著。(4)两组大鼠血压值比较,恐惧模型组大鼠血压趋势呈持续升高,对照组无明显变化。第1周两组大鼠血压无显著性差异,第2周(P0.05)、3周(P0.01)、4周(P0.01)两组大鼠血压比较均差异显著。(5)两组大鼠心率比较,第1周两组大鼠心率无显著性差异,第2周(P0.05)、3周(P0.05)、4周(P0.01)两组大鼠心率比较均差异显著。(6)两组大鼠血清C反应蛋白含量比较,恐惧模型组在第1周(P0.05)、2周(P0.01)、3周(P0.01)、4周(P0.01)均显著高于对照组;(7)两组大鼠血清肌酸激酶同工酶含量比较,恐惧模型组大鼠血清肌酸激酶同工酶在第1、2、3周均无显著差异,第4周(P0.01)显著高于对照组,差异有统计学意义。(8)两组大鼠血清心肌钙蛋白I含量比较,恐惧模型组大鼠心肌钙蛋白I含量在第1周(P0.05)、2周(P0.01)、3周(P0.01)、4周(P0.01)均显著高于对照组,差异有统计学意义。 结论:本研究结果表明经过改良的Takashi法可以成功的制造大鼠恐惧应激模型。恐惧应激可以提高大鼠应激水平进而影响大鼠的体重、血压、心率、行为以及心血管指标的改变。部分实验备选指标可以为抗恐惧应激药物药效评价提供相关依据。
[Abstract]:Objective: to establish an experimental animal model of cardiovascular injury prevention and control drugs induced by conditioned fear stress in rats, and to observe the effects of fear stress on cardiovascular function in rats. Analysis, evaluation. To evaluate the efficacy of anti-fear drugs in order to establish an evaluation system in the future. Methods: 64 healthy male wistar rats were randomly divided into fear model group (n = 32) and control group (n = 32). After feeding free drinking water for 10 days, the fear model group was given 2s noise 3s foot current stimulation every day, the current intensity was 1 Ma, the interval was 30 times, the 1213 days repeated experiment, the control group was only given 2s noise daily. There was no plantar current stimulation, the interval was 1 min, 30 times. The experiment was repeated on the 12th day. On the 14th day, the changes of 6-30min behavior were recorded after 5min noise in the two groups, and the success of the model was evaluated. From the second day after the success of the model, the rats were given body weight, spontaneous activity, blood pressure and heart rate, serum Gao Min C-reactive protein and creatine kinase isozyme in the second day of the second day, respectively. Cardiac troponin I content was measured. Results: (1) on the 14th day, the behavioral responses after 5min noise in the two groups were observed. The freezing time of the fear model group was significantly longer than that of the control group. The difference was statistically significant (P0.05), which proved that the model was successful. (2) the body weight of the two groups were all called natural growth trend, and there was no significant difference in the body weight between the two groups at the first week. There were significant differences in body weight between the two groups at the 2nd week (P0.05) and the 4th week (P0.01). (3) the activity times of the fear model group were significantly lower than those of the control group at the 1st week (P0.05) and the 2nd week (P0.01) and the 4th week (P0.05), the difference was significant. (4) the blood pressure value of the two groups was significantly lower than that of the control group. The trend of blood pressure in the fear model group was continuously increased, but that in the control group was not significantly changed. In the first week, there was no significant difference in blood pressure between the two groups, but in the second week (P0.05) and the third week (P0.01) and the fourth week (P0.01), there were significant differences in blood pressure between the two groups. (5) there was no significant difference in heart rate between the two groups in the first week, and in the first week, there was no significant difference in the heart rate between the two groups. There were significant differences in heart rate between the two groups in the 2nd week (P0.05) and the 3rd week (P0.05) and the 4th week (P0.01). (6) the content of serum C-reactive protein in the two groups was higher than that in the control group. The level of serum creatine kinase isoenzyme in the fear model group was significantly higher than that in the control group at the 1st week (P0.05) and the 2nd week (P0.01) and the 4th week (P0.01) (P0.01). (7) there was no significant difference in serum creatine kinase isoenzyme content between the two groups. At the 4th week (P0.01), the difference was statistically significant. (8) compared with the control group, the level of cardiac troponin I in the fear model group was significantly higher than that in the control group at the 1st week (P0.05) and the 2nd week (P0.01) and the 3rd week (P0.01) and the 4th week (P0.01). The difference is statistically significant. Conclusion: the results of this study suggest that the modified Takashi method can successfully establish the rat model of fear stress. Fear stress can increase the stress level of rats and then affect the changes of body weight, blood pressure, heart rate, behavior and cardiovascular indexes. Some of the experimental alternative indicators can provide relevant evidence for the evaluation of the efficacy of anti-fear stress drugs.
【学位授予单位】:第二军医大学
【学位级别】:硕士
【学位授予年份】:2011
【分类号】:R-332

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