【作者】 刘翠清；

【导师】 赵锁安；

【作者基本信息】 河北医科大学 ， 生理学， 2003， 硕士

【摘要】 目的：观察不同周期足底电击结合噪音刺激对大鼠行为及心血管的影响；观察巴氯芬二次重复腹腔注入对非应激大鼠心血管与呼吸的影响；观察巴氯芬多次重复腹腔注入对应激大鼠心血管与呼吸的影响，及该反应是否与不同应激周期有关。 方法：采用足底电击结合噪音方法刺激大鼠，每日2次，每次2小时，连续应激15天；分别在应激前1天及应激第1、3、6、9、12、15天的应激后2小时用尾套法测量血压、心率，并观察其行为变化；制备不同应激周期模型，周期为应激1天、3天、6天、9天、12天、15天。巴氯芬二次重复腹腔注入乌拉坦麻醉的非应激大鼠及多次重复腹腔注入乌拉坦麻醉的不同应激周期大鼠，通过左股动脉插管、气管插管、光电指容换能器连接八道记录仪分别观察平均血压、心率、呼吸的变化。 结果：（1）大鼠应激后出现生长停滞、躁动不安、易于激惹等生理及行为的异常并伴交感紧张性增强的心血管改变。血压均显著升高（每次测得值均P＜0.01），至第6天达峰值，由应激前121.6±5.6mmHg升至158.3±7.5mmHg，第9天为152.8mmHg+5.8mmHg。此后在高水平维持，至第15天仍为150.5±7.1mmHg。心率在应激后第3-6天明显增快，由416±17次／分至第三天增为436±23次／分 中文摘要 （尸<0.05），至第六大增为442士9次/分（尸<0.01），此后即开始有所下降。期间对照组大鼠血压、心率均无明显变化。 （2）二次重复注射对非应激大鼠的影响:结果观察到，实验组巴氯芬首次注入血压明显升高，由1 13.2士8.3 mmHg升至30分钟后的139.2士11.2^Hg（尸<0.05）并维持，至60分钟仍为139.7士21.7 mmHg（尸<0.05）;该升压反应被巴氯芬重复注射翻转，二次注射后30分钟降为120.3士20.4mmHg，与基础值已无显著性差异，P>0.05;心率变化不明显。单纯对照组、次数对照组给药30分钟后血压也明显升高，至60分钟仍持续（与基础值相比尸<0.01），至第90分钟（相当于二次注射后30分钟）测得血压值仍远高于基础值，尸<0.01。心率变化不明显。呼吸对药物的反应呈减慢趋势，但起效时间较晚。实验组在二次给药后30分钟才由116士16次/分降为92士10次/分，尸<0.01;一单纯对照组、次数对照组也在给药后90分钟才一与基础呼吸有显著差异，尸<0.01。容量对照组血压、心率、呼吸变化均无统计学意义。 （3）多次重复注射对不同应激周期大鼠的影响: 首次注射的影响:巴氯芬首次腹腔注入30分钟后，除应激6天组血压升高15.3士9.3 mmHg无一显著性差异 （P>0.05），应激9天组给药后60分钟变化才有统计学意义 （尸<0.05）外，其它各组用药后30分钟与给药前相比，即差异显著。各组上升情况为:对照组一L升26.0士9.5^Hg（p<0.05），应激l天组30.2士6.gmmHg（p<0.01），应激3天组26.0士6.6 mrnHg（p<0.01），应激12大组23.6士8.1mmHg（p<0.01），应激15天组27.9士10.2 mmHg（p<0.05）。各组给药后30分钟与给药后60分钟相比，差异无显著性。 中文摘要组间比较，应激6天组较对照组（尸<0.01）、应激1天组 （P<0.01）、3天组（P<0.05）、15天组护<0.01)升高幅度小，差异显著。各组心率给药前后变化比较及组间比较均P>0.05。呼吸频率在巴氯芬腹腔注入后呈减慢趋势。但在30分钟后只有应激15天组与给药前有显著性差异，下降23士11次/分（尸<0.05）;应激3天组、6天组直至给药后60分钟才出现明显变化，均尸<0.01;其它组变化差异不显著。各组给药后30分钟与给药后60分钟相比，只有应激3天组变化有统计学意义，P<0.05。组间比较，各组与应激6天组无显著性差异。 之后给药的影响:①血压:二次给药后对照组及各应激组血压均明显降低。药后血压变化，应激6天组降低27.0士28.0 mmHg（尸<0.05），对照组及其它各应激组依次为19.4士3 .2 mmHg，13.1士12.5 mmHg，32.6士16.3 mmHg，19.8士19.0 mmHg，31.2士20.2 mmHg，33.7士15.5 mmHg，均尸<0.01。组间比较，各组与应激6天组无显著性差异。三次、四次给药时，血压更呈明显下降，各组尸<o.otl。两次给药各组分别与应激6天组比较差异均无显著性。②心率，只在第四次给药时，应激1天组下降13士7次/分、3大组下降18士17次/分、9天组下降14士10次/分，除这儿组变化显著尸<0.01外，其它组变化无统计学意义。儿个剂量时分别做组间比较，在4mg爪g剂量时，应激3大组与应激6天组差异显著，尸<0.05;sm叭g剂量时，应激1天组心率加快，应激6大组与之差异显著，P<O.05;其它变化均无显著性。③呼吸:二次给药，呼吸频率减慢。除应激6天组变化不明显外，其它组均显著降低:对照组下降11士8 中文摘要次/分（尸<0.05），应激9天组16士18次/分，1天组18士9次/分，3天组24士16次/分，₁2天组22士15次/分，15天组24士15次/分，均尸<0.01;组间比较，应激6天组比3天组、12天组、巧天组下降幅度低，均尸<0.05。三次注射时，各组呼吸频率明显减慢;组间比较，6天组比对照组、12天组降低明显，尸<0.05。第四次给药，呼吸更多还原

【Abstract】 Objective: To observe the behavior and cardiovascular effects of repeated electric foot-shock combined with noise in rats of different stress cycles; To investigate the cardiovascular and respiratory response to repeated administration of Baclofen in normotensive (non-stress) rats and stress rats of different cycles and to determine whether the response would be involved in different stress cycles.Methods: (1) The experiments were performed on male Wistar Rats. Rats were stimulated by repeated electric foot-shock combined with noise from a buzzer to establish conditional reflex, receiving stress twice daily, 2 hours per time, and the treatment lasted for 15 days. The BP and H.R were measured by tail cuff method 2 hours after stress respectively 1 day before and on the 1st, 3rd, 6th, 9th, 12th, 15th day of the stress. Their behavior was also observed. Stress models of different cycles, including 1-day, 3-day, 6-day, 9-day, 12-day, 15-day-stress, were made in this way. (2) Baclofen (Bac) was twice-repeated administered intraperitoneally into urethane-anesthetized non-stress rats and several-time-repeated into urethane-anesthetized stress rats with different cycles. Mean Blood Pressure (MBP), HeartRate (H.R) and Respiration Rate (R.R) were continuously recorded through Maclab/8S, by a light-electric energy conversion apparatus and two catheters, inserted into left femoral artery and the trachea.Results: (1) The stressed rats stagnated to grow, being restless, nervous and easy to be angry, accompanied by enhanced sympathetic action. Blood Pressure elevated significantly after stress (all P<0.01), from 121.6 ± 5.6 mmHg to the peak 158.3±7.5mmHg 6 days later, 152.8 mmHg±5.8 mmHg 9 days later, and maintained at the high level, still 150.5 ± 7.1mmHg after 15-day stress. Heart Rate increased only after 3-day stress, from 416±17 beats/min to 436±23 beats/min, (P<0.05), until the 6th day, increased to 442 ± 9 beats/min (P<0.05); thereafter decreased slowly. During the process, there was no significant changes in BP or H.R in control group rats.(2) Effects of twice-repeated injection into non-stress rats: In the experimental group (Bac-Bac), first treatment with Baclofen produced a marked and prolonged increase in MBP, from 113.2 ± 8.3 mmHg to 139.2±11.2 mmHg 30 minutes later (P<0.05), maintained at the level, 139.7 ± 21.7 mmHg 60 minutes later (P<0.05 ) .The pressor response was reversed to 120.3 ± 20.4 mmHg by second treatment (compared with the initial level, P>0.05), accompanied with no effects on H.R. In the control group (Bac-None) and the frequency control group (Bac-NS), the similar effects were observed with firsttreatment. But when the second administered, MBP was still different from its initial level (P<0.01), with no significance in PR (P>0.05). Responses of R.R appear descending at later time. That of experimental group fell from 116± 16 beats/min to 92±10 beats/min (P<(). 01) until 30 minutes after second injection. At the same time point, R.R of the control group and the frequency control group differed from that of respective baseline, P<0.01. In the volume control group, values were all unaltered in MBP, H.R, R.R, P>0.05.(3) Effects of several-time repeated injection into stressed rats: 30 minutes after the first Baclofen, similar pressor effects were observed. Except 6-day-stress increased 15.3 ±9.3 mmHg (not significant) and 9-day-stress groups (significant 60mins later), the increases were significant in other groups. The control group increased 26.0±9.5mmHg (P<0.05), 1-day-stress group 30.2 ± 6.9 mmHg (P<0.01), 3-day-stress group 26.0±6.6 mmHg (P<0.01), 12-day-stress 23.6±8.1mmHg (P<0.01), 15-day-stress group 27.9±10.2 mmHg (P<0.01). There was no significance between 30mins and 60mins after administration in all groups. Compared with 6-day-stress group, the increased amplitude of the control group(P<0.01), l-day-stress(P<0.01), 3-day-stress(P<0.05), 15-day-stress (P<0.01) groups were more marked. There was no diffirence in H.R between pre- and post-treatments.更多还原