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作 者:魏文树[1] 卢晓欣[2] 史道华[1] 魏炜明[3] 曾昭全[1] 刘锡钧[1]
机构地区:[1]南京军区福州总医院药理科,福州350025 [2]南京军区福州总医院高压氧科,福州350025 [3]南京军区福州总医院肝胆外科,福州350025
出 处:《第二军医大学学报》2004年第5期524-526,共3页Academic Journal of Second Military Medical University
摘 要:目的:观察大鼠高压氧暴露(HBO)对硝酸甘油(NTG)效应的影响,探讨NTG耐受性形成的机制。方法:20只大鼠随机分为常压空气吸入对照组(n=7)、NTG连用组(NTG 10 mg/kg皮下给药,每日3次,连用6 d,n=6)和HBO组(350 kPa压力下纯氧吸入120 min,每日1次,连续4 d,n=7)。以静注NTG后鼠尾容积变化评定耐受性,最后测定血管组织亚硝酸盐(NO2-)、总硝酸盐(NOx-)、氧自由基(O2-)、超氧化物歧化酶(SOD)活力和丙二醛(MDA)水平,并与对照组进行比较。结果:HBO使舌静脉注射NTG增加鼠尾容积的作用明显减弱,主动脉组织中的NO9-明显降低,O2-和MDA含量显著增高。这些结果与NTG连用组相似。另外,NTG连用引起NOx-明显升高和SOD活力明显下降,而HBO组则无明显变化。结论:HBO可引起与NTG连续应用相似的耐受性,表明氧化应激血管组织O2-产物升高是硝酸酯类耐受性形成的重要机制;连续应用NTG出现O2-增高可能与SOD活力降低也有关系。Objective: To study the development mechanism of tolerance to nitrogiycerin (NTG) by hyperbaric oxygen (HBO) in rats. Methods: Twenty Sprague-Dawley male and female rats, weighing (177 ? 5) g, were divided into 3 groups: normal control group(n = 7) , HBO group (pure oxygen inhalation at 350 kPa for 120 min once daily for 4 d,n = 6), and NTG group (10 mg/kg, sc 3 times a day for 6 d,n = 7). Rat tail volume was used as parameter for the effect of NTG(10 mg/kg iv), which was measured by plethysmometry before and after the HBO exposure and continuous use of NTG, respectively. The nitrite (NO2-) , total nitrate (NOx- ), oxygen free radical (O2- ), superoxide dismutase(SOD) activity, and malonaldehyde (MDA) in aorta were determined at the end of the experiment. Results : The increase of rat tail volume by NTG iv was significantly attenuated after the HBO exposure and continuous NTG use. At the same time, the NO2- in aorta was reduced, and the O2- and MDA were increased in both HBO group and NTG group. The NOx- was increased and the SOD activities was significantly reduced in the NTG. Conclusion: Continuous administration of NTG and HBO exposure can result in development of NTG tolerance in rats .which may be related to the O2- increase in vascular tissues. The increased O2- oxygen free radical productions during long-term NTG use may, at least partly, result from the decreased SOD activity.
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