GABA_B受体激动剂对应激大鼠心血管与呼吸的影响
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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20.4
    mmHg,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8.1
    mmHg(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    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    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
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), Heart
    
    
    Rate (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 first
    
    
    treatment. 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.
引文
1 杨钢,朱宜莲.应激时内分泌的异常.内科急危重症杂志.1998,4(3):97~99
    2 陆利民,汪军,姚泰.血管紧张素在紧张应激引起大鼠血压升高中的作用.生理学报,2000,10,52(5):371~374
    3 朱大年.肾上腺皮质激素在应激性高血压发病中的中枢机制.生理科学进展,1996,27(4):324~326
    4 李华,左伋做.GABA_B受体及其临床意义.中国临床神经科学,2001,9(1):96~98
    5 Angelo M. Taveira, Da Silva. Bryce Hartley. Respiratory depressent effects of GABA A-and B-receptor agonists in the cat. J. Appl. Physiol, 1987, 62(6): 2264~2272
    6 Olivier Pierrefiche, Arthur S. Foutzs and Monique Denavit-Saubie. Effects of GABA_B receptor agonists and antagonists on the bulbar respiratory network in cat. Brain Research, 1993,605:77~84
    7 John A. Heg, Garfield Mingo, et ai. Respiratory effects of baclofen and 3-aminoprophylphosphinic acid in
    
    guinea-pigs. Br. J of Pharmacology, 1995, 114:735~738
    8 Stephen M. Johnson, Jeffrey C. Smith, Jack L. Feldman. Modulation of respiratory rhythm in Vitro: role of Gi/o protein-mediated mechanisms. J Appl. Physiol, 1996,80(6): 2120~2133
    9 Teresa Trippenbach, Norma Lake. Excitatory cardiovascular and respiratory effects of baclofen in intact rats. Can. J. Physiol. Pharmacoi, 1994, 72:1200~1207
    10 Erin Seifert, Teresa Trippenbach, Effects of baclofen on the Hering-Breuer inspiratory-inhibitory and deflation reflex in rats. Am J. Physiol. 274 (Regulatory Integrative Comp. Physioi, 1998, 43:R462~R468
    11 陆月明.GABA对呼吸系统的作用.国外医学呼吸分册,1996,16(2):78~80
    12 Hausler-A, Monnet-G, Peter-O. Involvement of GABA_B receptors in the regulation of the hypothalamo-pituitary-adrenocortical (HPA) axis in rats. Steroid Biochem. Molec Biol, 1993, Vol.46, No.6, pp:767~771
    13 K.Takenaka, S.Sasaki, K.Nakamura. Hypothalamic and medullary GABA_A and GABA_B-ergic systems differently regulate sympathetic and cardiovascular systems. Clinical and Experimental Pharmacology and Physiology, 1995, Suppl. 1: S48~S50
    14 Ken Takenaka, Susumu Sasaki. Et al. GABA_B-ergic stimulation in Hypothalamic pressor area induces larger
    
    sympathetic and cardiovascular depression in Spontaneously Hypertensive rRats. Am J Hypertens, 1996, 9:964~972
    15 陆利民,汪军,李海燕.下丘脑加压素在紧张应激引起大鼠血压升高反应中的作用.高血压杂志,1999.3,7(1):79~83
    16 金玉祥,陆嘉峰等.应激性防御反应对大白鼠脑内C-FOS癌基因的表达及痛阈变化的关系.中国神经科学杂志,2000(6),16(2):147~150
    17 Lin Qing, Li Peng. Effects of chronic stress on Blood Pressure and Heart rate in Rats. Chinese Journal of Physiological Sciences, 1990, 6(2): 101~107
    18 罗基花,胡尚嘉,孙红霞.应激对大鼠行为及血压的影响.吉林医学院学报,1996,16(3):3~4
    19 Loris A Chahl, S.Belinda Walker. The effect of baclofen on the cardiovascular system of the rat. J. Pharmac, 1980,69:631~37
    20 丁寿根.应激过程中下丘脑-垂体-肾上腺轴的调控机理.国外医学军事医学分册,1994,11(1):9~14
    21 Jennifer Ong, David I.B.Kerr. GABA-receptors in Peripheral tissues. Life Sciences, 1990, Vol.46, pp: 1489~1501
    22 周云平.人垂体前叶功能的GABA能调节.国外医学.内分泌学分册,1989,(2):60~63
    23 刘少君,邱建勇,鞠躬.γ-氨基丁酸,谷氨酸能神经纤维在大鼠垂体前叶的分布,神经科学1996.03.25,3(1):
    
    46~48
    24 汪萌芽,朱蓉.解痉药巴氯芬研究进展.中国药理学通报,1992.OCT,8(5):335~339
    25 高东明,孙得玉.B型GABA受体研究进展.生理科学进展,1995,26(3)246~248
    26 储祥平.Ach,GABA在RVLM心血管活动调节中的作用.国外医学生理病理科学与临床分册,1998,18(2):128~31
    27 邹冈.基础神经药理学2版.北京.科学技术出版社,1995.5:135~152.
    28 K.Takenaka, S.Sasaki, K.Nakamura. Hypothalamic and medullary GABA_A and GABA_B-ergic systems differently regulate sympathetic and cardiovascular systems. Clinical and Experimental Pharmacology and Physiology, 1995, Suppl. 1:S48-S50
    29 罗基花 曲娴 孙红霞.应激对大鼠血浆皮质酮含量的影响.吉林医学院学报,1996,16(3):1~2
    30 杨权.下丘脑-垂体-肾上腺皮质轴应激反应的中枢机制.生理科学进展,2000,31(3):222~226
    31 张素珍,徐永,万瑜.应激时大鼠垂体前叶血管紧张素原基因表达增强.中国病理生理杂志,2002,18(5):540~542
    32 陆利民,汪军,姚泰.血管紧张素Ⅱ在紧张应激引起大鼠血压升高中的作用.生理学报,2000,52(5):371~375
    33 尹建如,杨刚.血管紧张素与肾上腺.生理科学进展,1996,27(1).70~72
    
    
    34 戴秀中 潘燕霞 郑庆玲.应激性血压增高时交感紧张性与动脉压力感受反射的变化.中国循环杂志,1995,10(3):166~169
    35 Kunos G, Varga K. The tachycardia associated with the defense reaction involves activation of both GABA_A and GABA_B receptors in the nucleus tractus solitarii. Clin.Exp.Hypertens, 1995, 17:91~100
    36 彭有清,杨军,殷明.大鼠孤束核GABA_A和GABA_B受体对心血管活动调节的区别.第二军医大学学报,1999,Feb,20(2):94~96
    37 Alberto Florentino, Karoly Varga and George Kunos. Mechanism of the cardiovascular effects of GABA_B receptor activation in the nucleus tractus solitarii of the rat. Brain Research, 1990, 535:264~270 Elsevier
    38 Persson B. A hypertensive response to baclofen in the Nucleus Tractus Solitarii in rats. J.Pharm. Pharmacol,1981, 33:226~231
    39 Vijayender Rao Durgam, Melissa Vitela, Steven W. Mifflin. Enhanced γ-Aminobutyric Acied-B receptor agonist responses and mRNA within the Nucleus of the Solitary Tract in hypertension. Hypertension, 1999, 33[part-Ⅱ]: 530~536
    40 Bengt Persson, Matts Henning. Central cardiovascular and biochemical effects of baclofen in the conscious rat. J Pharm. Pharmacol, 1980, 32:417~422
    41 朱长庚,张喜京等.大鼠神经垂体后叶加压素神经分
    
    泌末梢的GABA能神经支配的免疫电镜证实.解剖学报,1994.7,25(3):232~235
    42 姚泰,乔健天.生理学 第五版.人民卫生出版社:308
    43 李智,何瑞荣.动脉压力感受器反射与高血压.生理科学进展,1989,2013:210~214
    44 Ming Yin, Alan F. Sved. Role of γ-Aminobutyric Acied-B receptors in baroreceptor reflexes in hypertensive rats. Hypertension, 1996, 27:1291~129

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