外周α1受体作用参与应激对颈动脉窦反射的抑制

目的：探讨外周α1受体是否影响应激对颈动脉窦反射(carotid sinus reflex,CSR)的重调定。方法：应激1周的SD大鼠，麻醉后孤离双侧颈动脉窦区，将不同窦内压(intracarotid sinus pressure，ISP)与其对应的平均动脉压(meson arterial pressure，MAP)值进行Logistic五参数曲线方程拟合，求得ISP-MAP关系曲线及其特征参数，观察外周静脉注射选择性α受体拮抗剂酚苄明(phenoxybewamine，PBZ)对CSR的影响。结果：静脉注射PBZ(3μmoL／L，0．15μL／g)导致应激大鼠ISP(MAP关系曲线的后半程显著下移(P&;lt;0．05)，反射参数中阈压、饱和压和最大增益时的窦内压值分别从(128．37&;#177;10．05)mmHg(1mmHg=0．133kPa)、(205．15&;#177;12．18)和(166．72&;#177;11．35)mmHg减少至(116．41&;#177;8．51)．(188．15&;#177;11．77)和(152．28&;#177;9．30)mmHg(F=6．60、8．05和7．75．P&;lt;0．05)；静脉注射相同剂量的PBZ对非应激大鼠的CSR无明显影响(P&;gt;0．05)；静脉注射PBZ不能使应激的CSR水平恢复到非应激给药后水平。结论：外周α1受体参与应激对CSR的抑制性重调定；除此之外，应激作用中尚有其他因素的参与。     

外周α受体参与慢性应激大鼠颈动脉窦反射的重调定

目的：探讨外周α受体是否影响慢性应激对颈动脉窦反射（CSR）的重调定。方法：应激1周的大鼠，麻醉后孤离双侧颈动脉窦区，将不同窦内压（ISP）与其对应的平均动脉压（MAP）值进行Logistic曲线拟合，求得ISP－MAP关系曲线及其特征参数，观察外周静脉注射（iv）α受体拮抗剂酚妥拉明（PHEN）对CSR的影响。结果：（1）iv PHEN(20μg/100g体重）导致应激大鼠ISP－MAP关系曲线的后半程显著下移，反射参数中阈压（TP）、饱和压（SP）和最大增益时的窦内压（ISPGmax）值均减少（P＜0．05）。（2）iv相同剂量的PHEN对非应激大鼠的CSR无明显影响。（3）ivPHEN不能使应激的CSR水平恢复到非应激给药后水平。结论：外周α受体参与慢性应激对CSR的重调定。     

外周α2受体参与调制脑室注射组胺对颈动脉窦反射的重调定

目的研究外周α2受体是否参与调制中枢外源性组胺(HA)对颈动脉窦反射(CBR)的重调定.方法孤离麻醉SD大鼠的双侧颈动脉窦区,将不同窦内压(ISP)与其对应的平均动脉压(MAP)值进行Logistic五参数曲线拟合,根据所得ISP-MAP关系曲线及其特征参数,观察脑室注射(i.c.v.)HA以及预先外周静脉注射(iv.)选择性α2受体拮抗剂育亨宾(YOH)对CBR的影响.结果i.c.v.HA(60μmol·L-1,5μL)导致ISP-MAP关系曲线明显上移,反射参数中阈压增大(P＜0.05),MAP反射变动范围及反射最大增益减小(P＜0.05);预先iv.YOH(2.5μmol·L-1,15μL·100g-1体重),明显进一步加强HA的上述效应;单独iv.相同剂量的YOH对CBR无明显影响(P＞0.05).结论脑室给HA使CBR产生快速重调定,反射敏感性下降;外周α2受体作用可减弱i.c.v.HA对CBR的抑制性重调定.     

颈动脉窦压力感受性反射的数字仿真实验

目的：建立心血管系统数学模型，对动脉窦压力感受性反射进行数字仿真。方法：采用MATLAB／SIMULINK系统软件，建立整体心血管系统模型，并作大鼠的孤立窦实验。结果：仿真实验和动物实验所得到的压力反射曲线具有良好的一致性。结论：仿真模型具有可扩充性，可以作为动物实验的辅助工具。     

颈动脉支架植入致颈动脉窦反射1例

患者,女性,32岁,主因间断性晕厥12年入院。患者12年前开始出现间断性晕厥,多于卧位站起行走时发生,伴有意识丧失,每次持续10余秒至2分钟,未行诊治,1月前查体时上肢血压测不到,在当地医院查血管超声考虑多发性大动脉炎,为进一步诊治而入院。入院查体：营养中等,脉搏74次／min,左上肢血压测不到,     

α1受体在应激性溃疡中作用的实验研究

目的：探讨a1受体在应激性溃疡发病机制中的作用。方法：用放射自显影术显示胃粘膜下动脉a1受体，用激光多普勒血流仪测定胃粘膜血流。结果：胃体部粘膜下动脉的a1受体分布密度（617.7士39.9）明显高于胃窦部（474.4士22.7），P＜0．o1。应激时给予小剂量a受体阻断剂能明显改善胃粘膜血流（P＜0.001和P＜0．01），使胃粘膜损伤减轻（P＜0．001）。结论：交感-肾上腺素系统对胃体部粘膜血流作用大于胃窦部，可能是应激性溃疡好发于胃体部的一个重要原因；小剂量a受体阻断剂能够预防和治疗应激性溃疡。     

心脏β2,α1及AT1受体自身抗体与原发性高血压的相关性

目的研究受体与自身抗体在高血压发病中的作用机制,探讨抗 G 蛋白偶联家族中β 2,α 1及 AT1受体的自身抗体在原发性高血压病程进展中的分布情况.方法应用酶联免疫吸附测定 (ELISA) 技术,以细胞外第二环表位肽段的合成肽作为抗原,检测 50例高血压心脏病、 40例单纯高血压和 40例正常人血清中抗 G 蛋白偶联家族中β 2、α 1和 AT1受体的自身抗体.结果高血压心脏病患者血清中抗 G 蛋白偶联型β 2、α 1和 AT1受体自身抗体的阳性率明显高于单纯高血压和正常对照组 (χ 2=3.85～ 13.5,P< 0.05); 高血压心脏病自身抗体阳性的平均几何抗体滴度与单纯性高血压比较无明显差异 (t=1.41～ 1.88,P >0.05),但两组阳性抗体的平均几何滴度均明显高于正常对照组 (t=2.51～ 6.61,P< 0.05); 高血压心脏病抗β 2受体自身抗体阳性患者,其中 81%的患者同时具有α 1受体的自身抗体; 76%的患者同时具有 AT1受体的自身抗体; 52%的患者存在上述 3种受体的自身抗体.结论抗 G 蛋白偶联型β 2,α 1和 AT1受体的自身抗体参与原发性高血压的病理生理过程,可能与心肌和血管重构有关.通过检测抗 G 蛋白偶联家族中与心血管疾病相关的自身抗体,可能对预测高血压病程及心肌和血管病变程度有一定的参考价值,也可能为临床选择联合降压治疗提供参考依据.     

α1受体阻滞剂药物对高血压的治疗作用

高血压病的药物治疗对减少高血压并发症,例如脑血管意外、充血性心力衰竭和肾脏病变是有效的,但是未能降低冠心病和心肌梗塞的发生率。某些降压药物治疗中的危险因素往往超过本身治疗的价值,尤其是与冠心病相关的因素。高血压病阶梯疗法中第一梯级药物噻嗪类利尿剂或β受体阻滞剂在长程治疗中能引起血清总胆固醇、低密度脂蛋白(LDL)和甘油三酯的升高。所以从抗高血压治疗的整体策略来说,合理的降压治疗应该减低冠心病的所有危险因素。由于降低体循环的血管阻力(SVR),纠正高血     

内质网应激在百草枯上调缺氧诱导因子1α中的作用

目的：探讨内质网应激在百草枯（PQ）上调缺氧诱导因子1α（HIF-1α）中的作用。方法：将60只雄性SD大鼠按照随机数字表法分为对照组（10只）和染毒组（50只）,染毒组按照50mg/kg的标准将20%的PQ用生理盐水稀释到1ml进行一次性灌胃,于灌胃后2、6、12、24、48h处死动物取肺组织。提取肺组织总蛋白,采用Western Blotting检测HIF-1α和内质网应激标志物GRP78、XBP1的表达。选择ERS抑制剂4-苯基丁酸进行预处理,再施以PQ暴露,Western Blot和免疫荧光检测肺组织中GRP78及HIF-1α的表达。结果：染毒后2h肺组织中HIF-1α、GRP78和XBP1蛋白表达均较对照组明显升高,随时间延长,逐步增高。采用4-苯基丁酸抑制处理后,与PQ处理组比较,大鼠肺组织中GRP78、HIF-1α表达减少。结论：PQ进入肺组织后,可能通过诱导ERS上调HIF-1α的表达参与肺纤维化。     

不同时间缺血预处理和不同剂量α1受体激动剂对兔缺血心肌保护作用的实验研究

目的：观察不同时期短暂缺血预处理及不同剂量α１受体激动剂对预处理的心肌保护作用的影响,初步探讨预处理机制。方法：将家兔分为７组,除对照组外分别给予不同时间缺血预处理及不同浓度α１受体预处理。结果：各预处理组兔心脏经３０分钟持续缺血时均较对照组心肌梗塞面积减少（Ｐ＜００５）;各预处理组间的心肌梗塞面积无显著差别。结论：缺血预处理及α１受体激动剂对心肌缺血性损伤的保护作用在达到某一可引起预处理效应的阈值时即能产生,其程度不随预处理剂量改变而改变;α１受体参与了预处理保护作用的产生。     

Effect of isometric hand-grip exercise on the carotid sinus baroreceptor reflex in man

1. The changes in R--R heart interval that result from step-increase and step-decrease in carotid sinus transmural pressure induced by a variable pressure neck chamber were measured in seven normal men. Observations were made at rest, and during isometric hand-grip exercise at 24%, 44% and 64% of maximal voluntary contraction. 2. The response of heart interval to increase in carotid sinus transmural pressure was progressively and markedly diminished according to the strength of hand-grip. This effect was fully developed from the moment of onset of the exertion. 3. The response of heart interval to decrease in carotid sinus transmural pressure was much less consistently affected by hand-grip exercise.     

Mutual interactions of respiratory sinus arrhythmia and the carotid baroreceptor-heart rate reflex.

1. In six healthy subjects the amplitude and phase of respiratory sinus arrhythmia were determined at five different respiratory cycle lengths ranging from 3 to 9.5 s. 2. At each respiratory cycle length the carotid baroreceptor-heart rate reflex response was determined by cyclical neck suction at -40 mmHg at five different cycle lengths covering the same range of 3-9.5 s. 3. The application of cyclical neck suction increased the amplitude of respiratory sinus arrhythmia in all but the longest respiratory cycle lengths. 4. With increasing respiratory cycle length the amplitude of sinus arrhythmia increased, and R-R intervals were at their longest at an earlier phase of the respiratory cycle. Similarly, with increasing suction cycle length the amplitude of the cardiac interval response increased and the phase angle decreased. 5. The cardiac interval responses to respiration and to neck suction at different frequencies were independent of each other, the heart rate at any moment resulting from the algebraic summation of the two responses.     

The role of melanin-concentrating hormone-1 receptors in the voiding reflex in rats

We have used the selective melanin-concentrating hormone-1 (MCH(1)) receptor antagonist SNAP 7941 [((+)-methyl (4S)-3-{[(3-{4-[3-(acetylamino)phenyl]-1-piperidinyl}propyl) amino]carbonyl}-4-(3,4-difluorophenyl)-6-(methoxymethyl)-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxylate hydrochloride)] to investigate the role of the hypothalamic neuropeptide MCH in the control of voiding in rats. Intravenous administration of SNAP 7941 (3 and 10 mg/kg i.v.) produced dose-related inhibition of rhythmic, distension-induced voiding contractions in anesthetized rats. In conscious rats in which repeated voiding cycles were evoked by continuous slow transvesicular infusion of saline, intragastric SNAP 7941 [0.03-1 mg/kg intragastrically (i.g.)] produced sustained increases in infusion capacity (maximum = 220% basal), comparable with the effects of the 5-hydroxytryptamine(1A) antagonist WAY 100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-cyclohexanecarboxamide maleate salt), and the muscarinic antagonist, oxybutynin (4-diethylaminobut-2-ynyl 2-cyclohexyl-2-hydroxy-2-phenylacetate hydrochloride). SNAP 7941 produced similar results when administered at a low dose (0.01 nmol) into the lateral ventricle (intracerebroventricular). The opposite effect was produced when MCH (20 nmol) was delivered intracerebroventricularly, resulting in a 34% decrease in apparent bladder capacity with increased urinary frequency. The effect of MCH was blocked by the prior intragastric administration of SNAP 7941 (0.1 mg/kg), but oxybutynin (1 mg/kg) was ineffective. Finally, in conscious spontaneously hypertensive rats, SNAP 7941 (0.1 mg/kg i.g.) produced a 31% reduction in micturition frequency, accompanied by a 36% increase in bladder capacity, with no effect on total volume voided over 6 h. The data indicate that MCH acts via MCH(1) receptors within the CNS to modulate the voiding reflex in rats. The striking effects of the MCH(1) antagonist SNAP 7941 to increase bladder capacity and reduce voiding frequency indicate that MCH(1) antagonists may offer a potential novel approach for treating overactive bladder syndrome.     

Lack of effect of isometric handgrip exercise on the responses of the carotid sinus baroreceptor reflex in man

1. The change in arterial pressure and heart rate resulting from alteration of carotid sinus transmural pressure by a median--34 mmHg and +33 mmHg by means of a variable-pressure neck chamber was tested in seven male volunteer subjects, at rest and during exertion of 35, 45 and 65% of maximum voluntary handgrip. 2. During 60 s of 35 and 45%, and during 30 s of 65%, of maximal voluntary handgrip there was virtually no alteration of the response of blood pressure to alteration carotid sinus transmural pressure. 3. The bradycardic response to increase in carotid sinus transmural pressure was reduced at various times after the commencement of handgrip at 45 and 65% of maximum voluntary contraction. 4. It is concluded that a reduction in arterial baroreceptor reflex sensitivy does not play an important role in the initiation of the increase in arterial blood pressure and heart rate caused by isometric exercise. 5. The hypothesis is advanced that some of the cardiovascular changes in exercise may result from elevation of the central 'set point' for blood pressure.     

Persistent deep mechanical hyperalgesia induced by repeated cold stress in rats

Chronic muscle pain of the neck, shoulder and low back is quite common and often related to a stressed condition. In this study we tried to make a model of long-lasting muscle mechanical hyperalgesia based on one type of stress, repeated cold stress (RCS) (Kita T, Hata T, Yoneda R, Okage T. Stress state caused by alternation of rhythm in environmental temperature, and the functional disorders in mice and rats. Folia Pharmacol Jpn 1975;71:195–210). We first validated a method of measuring the muscle mechanical nociceptive threshold through skin, with surface anesthesia of the skin covering the muscle. We found that a pressure test using a Randall–Selitto analgesiometer equipped with a larger probe (? 2.6 mm) can measure the deep mechanical withdrawal threshold even under the presence of cutaneous punctuate hyperalgesia. RCS was performed by changing the temperature from 22 °C to either 4 °C (RCS at 4 °C) or ?3 °C (RCS at ?3 °C) every 30 min, and then maintained at 4 °C/?3 °C from 17:30 to 10:00 the next day. RCS at 4 °C for 5 days induced bilateral deep mechanical hyperalgesia lasting 2–3 weeks without cutaneous punctuate hyperalgesia. Deep mechanical hyperalgesia observed after RCS at ?3 °C lasted longer (～6 weeks) and was severer than RCS at 4 °C. Bilateral cutaneous punctuate hyperalgesia was also observed with RCS at ?3 °C. Intramuscular injection of lidocaine confirmed that the muscle was hyperalgesic. RCS might serve as a useful model for study of the mechanism of chronic muscle pain and its treatment.     

甘草苷对慢性应激抑郁模型大鼠的抗抑郁作用

目的：观察甘草苷对慢性抑郁模型大鼠的疗效，探讨其抗抑郁样作用的可能机制。 方法：实验于2005—06／07在北京大学医学部完成。72只成年雄性SD大鼠，根据其体质量采用区组随机化的方法将大鼠分为6组，每组12只：正常对照组、模型组（应激＋灌胃双蒸水）、氟西汀组（应激＋灌胃氟西汀），以及甘草苷10mg／kg、20mg／kg、40mg／kg组（应激＋灌胃甘草苷）。采用慢性应激加孤养造模，应激持续5周，从第3周起进行药物干预。盐酸氟西汀原料药由常州四药公司提供。甘草苷由北大药学院生药学生物技术研究室提供。采用糖水消耗实验和强迫游泳实验观察大鼠行为学改变。实验结束后断头取血，分离血浆和红细胞，用试剂盒测定红细胞超氧化物歧化酶活性和血浆丙二醛浓度。 结果：实验中，1只大鼠脚趾受伤，2只造模时意外溺亡，共69只大鼠进入结果分析。①慢性应激大鼠糖水消耗量较正常对照组明显降低[（8.3&;#177;0.9），（14．4&;#177;0.8）g，P〈0．01]；治疗后糖水消耗量增加，差异均具有显著性[甘草苷10、20、40mg／kg组分别为（11．4&;#177;1．2），（14．1&;#177;1．0），（14．0&;#177;0．8）g，氟西汀组为（13．0&;#177;1.9）g，P〈0．05或0．01]。②与对照组相比，模型组大鼠不动时间显著延长[（37&;#177;9），（96&;#177;10）s，P〈0．01]；与模型组相比，给药各组大鼠的不动时间均显著缩短[甘草苷10、20、40mg／kg组分别为（66&;#177;10），（26&;#177;8），（41&;#177;11）s，氟西汀组为（63&;#177;8）s，P〈0．05或0．01]。③模型组红细胞超氧化物歧化酶活性低于正常对照组[（35．4&;#177;6．8），（44.5&;#177;4．6）μkat／g，P〈0．01]；甘草苷各组后超氧化物歧化酶活性均高于模型组[20、40mg／kg组分别为（42.2&;#177;3．8）μkat／g，P〈0．05；（45．3&;#177;7．9）μkat／g，P〈0.01]；氟西汀组超氧化物歧化酶活性与模型组相比差异无显著性。④模型组血浆丙二醛浓度高于正常对照组[（3．4&;#177;0．6），（1．9&;#177;0．4）μmol／L，P〈0．01]；甘草苷治疗组血浆丙二醛浓度降低[20、40mg／kg组分别为（2.2&;#177;0.9）μmol／L，P〈0．05；（1．9&;#177;0．7）μmol／L，P〈0.01]。 结论：甘草苷可以改善抑郁模型中快感缺乏的症状，并能对抗绝望行为，支持甘草苷具有抗抑郁样作用的假设。甘草苷抗抑郁样作用可能通过提高机体超氧化物歧化酶活性，清除自由基，阻止脂质的过氧化，减少丙二醛的生成实现的。     

甘草苷对慢性应激抑郁模型大鼠的抗抑郁作用

目的:观察甘草苷对慢性抑郁模型大鼠的疗效,探讨其抗抑郁样作用的可能机制。方法:实验于2005-06/07在北京大学医学部完成。72只成年雄性SD大鼠,根据其体质量采用区组随机化的方法将大鼠分为6组,每组12只:正常对照组、模型组(应激 灌胃双蒸水)、氟西汀组(应激 灌胃氟西汀),以及甘草苷10mg/kg、20mg/kg、40mg/kg组(应激 灌胃甘草苷)。采用慢性应激加孤养造模,应激持续5周,从第3周起进行药物干预。盐酸氟西汀原料药由常州四药公司提供。甘草苷由北大药学院生药学生物技术研究室提供。采用糖水消耗实验和强迫游泳实验观察大鼠行为学改变。实验结束后断头取血,分离血浆和红细胞,用试剂盒测定红细胞超氧化物歧化酶活性和血浆丙二醛浓度。结果:实验中,1只大鼠脚趾受伤,2只造模时意外溺亡,共69只大鼠进入结果分析。①慢性应激大鼠糖水消耗量较正常对照组明显降低[(8.3±0.9),(14.4±0.8)g,P<0.01];治疗后糖水消耗量增加,差异均具有显著性[甘草苷10、20、40mg/kg组分别为(11.4±1.2),(14.1±1.0),(14.0±0.8)g,氟西汀组为(13.0±1.9)g,P<0.05或0.01]。②与对照组相比,模型组大鼠不动时间显著延长[(37±9),(96±10)s,P<0.01];与模型组相比,给药各组大鼠的不动时间均显著缩短[甘草苷10、20、40mg/kg组分别为(66±10),(26±8),(41±11)s,氟西汀组为(63±8)s,P<0.05或0.01]。③模型组红细胞超氧化物歧化酶活性低于正常对照组[(35.4±6.8),(44.5±4.6)μkat/g,P<0.01];甘草苷各组后超氧化物歧化酶活性均高于模型组[20、40mg/kg组分别为(42.2±3.8)μkat/g,P<0.05;(45.3±7.9)μkat/g,P<0.01];氟西汀组超氧化物歧化酶活性与模型组相比差异无显著性。④模型组血浆丙二醛浓度高于正常对照组[(3.4±0.6),(1.9±0.4)μmol/L,P<0.01];甘草苷治疗组血浆丙二醛浓度降低[20、40mg/kg组分别为(2.2±0.9)μmol/L,P<0.05;(1.9±0.7)μmol/L,P<0.01]。结论:甘草苷可以改善抑郁模型中快感缺乏的症状,并能对抗绝望行为,支持甘草苷具有抗抑郁样作用的假设。甘草苷抗抑郁样作用可能通过提高机体超氧化物歧化酶活性,清除自由基,阻止脂质的过氧化,减少丙二醛的生成实现的。