【摘要】 目的:观察在哮喘急性发作过程中,大鼠血浆中血管加压素、促肾上腺皮质激素和皮质醇以及下丘脑中血管加压素、促肾上腺皮质激素释放因子水平的变化,进而探讨急性哮喘发作对机体应激水平的影响以及血管加压素在此过程中的作用。方法:实验于2005-12/2006-07在南京医科大学生理学系实验室进行。①实验一:取32只大鼠单纯随机分为对照组、哮喘激发组、假激发组和生理盐水吸入组4组,每组8只。对照组腹腔注射生理盐水,其余大鼠腹腔注射卵蛋白致敏;实验开始第15天,对照组和哮喘激发组大鼠超声雾化吸入10g/L卵蛋白溶液20min,1次/d,连续3d,生理盐水吸入组雾化吸入10g/L生理盐水,假激发组不吸入任何蒸汽。②实验二:40只大鼠单纯随机分成对照组、假手术组、生理盐水组、侧脑室给药组和静脉给药组5组,每组8只;对照组腹腔注射生理盐水,其余大鼠腹腔注射卵蛋白致敏后第15天给药。侧脑室给药组侧脑室注射血管加压素受体阻断剂d(CH2)5Tyr(Me)AVP0.3μg;生理盐水组侧脑室注射1μL生理盐水;假手术组进行侧脑室操作,但不注射;静脉给药组按1mg/kg剂量静脉给与d(CH2)5Tyr(Me)AVP。给药1h后,雾化吸入10g/L卵蛋白溶液20min。如是处理,连续3d后。③实验完成后处死动物,放射免疫法分别测定下丘脑中促肾上腺皮质激素释放因子和血管加压素水平,以及血浆中血管加压素、促肾上腺皮质激素和皮质醇质量的浓度。结果:72只大鼠进入结果分析。①实验一结果:哮喘激发组血浆中血管加压素、促肾上腺皮质激素和皮质醇水平高于对照组[(7.92±0.97),(4.32±0.93)ng/L;(805.8±162.1),(279.7±88.5)ng/L;(12.02±1.25),(5.24±1.12)ng/L,P<0.05],生理盐水吸入组和假激发组高于对照组,但低于哮喘激发组(P<0.05)。哮喘激发组下丘脑中血管加压素和促肾上腺皮质激素释放因子水平高于生理盐水吸入组和假激发组[(17±1),(10±1),(11±2)pg;(7937±198),(6210±198),(6165±203)pg;P<0.05],以上3组均高于对照组(P<0.05)。②实验二结果:侧脑室给药组血浆中促肾上腺皮质激素和皮质醇水平为(480.4±101.7),(9.75±1.97)ng/L,低于假手术组、生理盐水组和静脉给药组,后3组间差异不显著。结论:①致敏过程使机体应激水平升高,同时下丘脑-腺垂体-肾上腺皮质轴的功能增强,可能是哮喘急性发作的重要原因之一。②降低下丘脑血管加压素的释放可以改善哮喘激发时的下丘脑-腺垂体-肾上腺皮质轴的功能亢进。更多还原

【Abstract】 AIM:To investigate the changes of contents of arginine vasopressin(AVP),cortisone and adrenocorticotropic hormone(ACTH)in the plasma and changes of AVP and corticotrophin releasing factor(CRF)in the hypothalamus of the asthmatic rats,and evaluate the effect of acute asthmatic process in the stress level of rats and the role of AVP.METHODS:The study was performed in the Department of Physiology in Nanjing Medical University from December 2005 to July 2006.In the first protocol,32 rats were divided into four groups randomly,with 8 rats in each.①control group,rats were sensitized to normal saline intraperitoneally and on the 15th day,they were challenged with 10 g/L ovalbumin(OA)by aerosol inhalation for 20 minutes,continuously 3 days;②asthma challenge group,rats were sensitized to OA intraperitoneally and challenged with OA as control group;③normal saline inhalation group,rats were sensitized to OA intraperitoneally and challenged with 10 g/L normal saline via aerosol inhalation;④sham group,rats were sensitized to OA intraperitoneally and challenged with nothing.In the second protocol,40 rats were divided into five groups randomly,with 8 rats in each.①control group,rats were sensitized to normal saline intraperitoneally;the remain animals were sensitized to OA intraperitoneally and divided into four groups.②administration group,the asthmatic rats received intracerebroventriculary AVP V1 receptor antagonist d(CH2)5Tyr(Me)AVP,0.3 μg.③normal saline group,the asthmatic rats were injected with intracerebroventriculary normal saline,1 μL.④sham operation group,the rats received intracerebroventriculary procedure without injection.⑤intravenous injection group,the asthmatic rats received intravenous injection with AVP V1 receptor antagonist,1 mg/kg.Animals were administrated for one hour and challenged with 10 g/L OA via aerosol inhalation for 20 minutes,continuously 3 days.All the rats were executed after the procedures were finished.The contents of AVP,cortisone and ACTH in plasma and the concentrations of hypothalamic AVP and CRF were measured by radioimmunoassay(RIA).RESULTS:All 72 rats were involved in the result analysis.①Result of the first protocol:Compared with control animals,the levels of ACTH,AVP and cortisone in plasma were increased in asthma challenge group [(7.92±0.97),(4.32±0.93)ng/L;(805.8±162.1),(279.7±88.5)ng/L;(12.02±1.25),(5.24±1.12)ng/L,P < 0.05].And the contents of normal saline inhalation group and sham group were higher than those of control group,but lower than those of asthma challenge group(P < 0.05).The concentrations of hypothalamic AVP and CRF were higher in asthma challenge group than in normal saline inhalation group and sham group,and those three groups were all higher than control group [(17±1),(10±1),(11±2)pg;(7 937±198),(6 210±198),(6 165±203)pg;P < 0.05].②Result of the second protocol:Intracerebroventricular injection of AVP V1 receptor antagonist could significantly reduce ACTH and cortisone content to(480.4±101.7)and(9.75±1.97)ng/L in plasma.There were no significant difference among sham operation group,normal saline group and intravenous injection group.CONCLUSION:①OA sensitization may lead to increase stress level and strengthen the function of hypothalamic-pituitary-adrenal axis,which is essential for the asthma challenge.②Decreased release of hypothalamic AVP may improve the hyperfunction of hypothalamic-pituitary-adrenal axis in the asthmatic process.更多还原