Study on myocardium and brain damage in rats by simulating high altitude
-
摘要: 目的 采用大型低压低氧动物实验舱模拟海拔6 000 m低氧低温环境，探讨不同暴露时间对大鼠心、脑组织损伤的程度，为建立大鼠急性高原病模型及其相关机制研究奠定基础。 方法 32只健康雄性Wistar大鼠随机分为正常对照组及低氧低温1、3、5 d组，每组8只。正常对照组大鼠饲养于当地海拔高度（1 500 m），不予处理；其余3组根据不同暴露时间置于低压氧舱模拟海拔6 000 m高原进行低氧低温处理。HE染色观察心、脑组织病理改变，并检测相关生化指标的变化，评价不同暴露时间对大鼠心、脑组织的损伤情况。 结果 HE染色结果显示，低氧低温引起大鼠心、脑组织不同程度的损伤，其中心肌组织在上述实验条件下随暴露时间的延长损伤加重，而脑组织在3 d时损伤最为严重；与正常对照组相比，各组心肌组织丙二醛（malondialdehyde，MDA）含量、乳酸（lactid acid，LD）含量随时间延长而明显增加（P<0.05或P<0.01），还原型谷胱甘肽（reduced glutathione，GSH）含量、总超氧化物歧化酶（total superoxide dismutase，T-SOD）、Na+K+-ATPase活力随时间延长而明显降低（P<0.05或P<0.01）；脑组织MDA含量在1 d及3 d时有显著升高（P<0.05或P<0.01），LD含量随时间延长而明显升高（P<0.05），GSH含量、T-SOD及Na+K+-ATP酶活力仅在3 d时降低最为明显（P<0.05）。 结论 模拟海拔6 000 m高原环境对大鼠心、脑组织造成明显损伤，且损伤程度与暴露于低氧低温的时间有关，机体抗氧化能力降低、自由基增加和能量代谢障碍是导致其损伤的重要因素。Abstract: Objective To investigate the effect of hypoxia with cold on the heart and brain damage in rats by simulating 6 000 m high altitude at different exposure time, established a rat model of acute mountain sickness for the related mechanism studies. Methods 32 healthy male Wistar rats were randomly divided into normal control group, hypoxia with cold 1 d, 3 d and 5 d group, 8 rats in each group. The normal control group was kept in the plain environment (1 500 m) without any treatment. The other three groups were placed in large hypobaric hypoxia chamber to simulate 6 000 m altitude with different exposed times. HE staining was used to observe the pathological changes of heart and brain tissue. The changes of biochemical indexes were measured to evaluate the damage of heart and brain tissue at different hypoxia times. Results HE staining showed that hypoxia with cold induced rat heart and brain damage with different degrees. The myocardial tissue damage was increased with exposure time. The most serious brain damage happened in day 3. Compared with the normal control group, the content of MDA and LD in the myocardial tissue of hypoxia rats were significantly increased (P<0.05 or P<0.01) with prolonged time, while the contents of GSH, T-SOD and the activity of Na+ K+-ATPase were reduced (P<0.05 or P<0.01). The content of MDA in brain tissue was significantly increased at day 1 and day 3 (P<0.05 or P<0.01). LD content was significantly increased (P<0.05) with time. The content of GSH, the activity of T-SOD and Na+ K+-ATPase were significantly reduced in day 3 (P<0.05). Conclusion Simulating an altitude of 6 000 m caused obvious damage on the heart and brain tissues of rats. The degree of damage was related to the exposure time to hypoxia with cold. The decrease of body's antioxidant capacity, the increase of free radicals and energy metabolism disorders are important factors leading to heart and brain injury.
-
Key words:
- hypoxia with cold /
- acute mountain sickness(AMS) /
- oxidative stress
-
[1] Luo Y, Yang X, Gao Y.Strategies for the Prevention of acute mountain sickness and treatment for large groups making a rapid ascent in China[J]. Int J Cardiol, 2013, 169(2):97-100. [2] Luks AM, Swenson ER, Bartsch P.Acute high-altitude sickness[J]. Eur Respir Rev, 2017, 26(143):160096. [3] Bultas J. Mountain sickness[J]. Cas Lek Cesk, 2015,154(6):280-286. [4] Boggild AK, Costiniuk C, Kain K C, et al. Environmental hazards in Nepal:altitude illness, environmental exposures, injuries, and bites in travelers and expatriates[J]. J Travel Med, 2007,14(6):361-368. [5] 白振忠. 高原鼠兔对缺氧、寒冷极端高原环境适应的分子机制研究[D]. 青海:青海大学, 2015. [6] 陈有, 李素芝, 黄学文, 等. 模拟高原环境大鼠AQP5表达和肺动脉压变化[J]. 西南国防医药,2009,19(1):4-6 [7] Ohinata A, Nagai K, Nomura J, et al. Lipopolysaccharide changes the subcellular distribution of aquaporin 5 and increases plasma membrane water permeability in mouse lung epithelial cells[J]. Biochem Biophys Res Commun, 2005,326(3):521-526. [8] Lisk C, McCord J, Bose S, et al. Nrf2 activation:a potential strategy for the prevention of acute mountain sickness[J]. Free Radic Biol Med, 2013,63:264-273. [9] 王雷琛, 姜艳, 张迪, 等. 虎杖苷对模拟高原低氧环境所致小鼠脑、肺损伤的保护作用[J]. 中南药学, 2015,13(4):343-348. [10] Norris JN,Viirre E,Aralis H,et al. High altitude headache and acute mountain sickness at moderate elevations in a military population during battalion-level training exercises[J]. Mil Med,2012,177(8):917-923. [11] Singh M, Thomas P, Shukla D, et al. Effect of subchronic hypobaric hypoxia on oxidative stress in rat heart[J]. Appl Biochem Biotechnol, 2013,169(8):2405-2419. [12] Heyman SN, Rosen S, Rosenberger C.A role for oxidative stress[J]. Contrib Nephrol, 2011, 174:138-148. [13] 张洁,袁东亚,李文华,等.氧自由基与高原病研究进展[J]. 医学综述, 2011,17(22):3384-3386. [14] Shi Q, Fu J, Ge D, et al. Huperzine a ameliorates cognitive deficits and oxidative stress in the hippocampus of rats exposed to acute hypobaric hypoxia[J]. Neurochem Res, 2012,37(9):2042-2052. [15] Sakr HF, Abbas AM, El Samanoudy AZ. Effect of vitamin E on cerebral cortical oxidative stress and brain-derived neurotrophic factor gene expression induced by hypoxia and exercise in rats[J]. J Physiol Pharmacol, 2015,66(2):191-202. [16] 马慧萍,吴金华,高荣敏,等.低压氧舱模拟急性高原缺氧动物模型建立的初探[J]. 解放军药学学报, 2013,29(4):301-304. [17] Mirtschink P, Krek W. Hypoxia-driven glycolytic and fructolytic metabolic programs:Pivotal to hypertrophic heart disease[J]. Biochim Biophys Acta, 2016, 1863(7 Pt B):1822-1828. [18] Cheng F,Xie S,Guo M, et al. Altered glucose metabolism and preserved energy charge and neuronal structures in the brain of mouse intermittently exposed to hypoxia[J]. J Chem Neuroanat, 2011, 42(1):65-71. -
点击查看大图
计量
- 文章访问数: 3224
- HTML全文浏览量: 413
- PDF下载量: 424
- 被引次数: 0
下载:
