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Volume 36 Issue 3
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Article Navigation >  Journal of Pharmaceutical Practice and Service  > 2018  >  36(3): 250-254

LUO Chuan, LI Jing, ZHANG Wannian, MIAO Zhenyuan. Discovery of bepridil as a valuable lead compound with potent p53-MDM2 inhibitory activity[J]. Journal of Pharmaceutical Practice and Service, 2021, 39(2): 126-129. doi: 10.12206/j.issn.1006-0111.202009031
Citation: WU Ningzi, MA HuiPing, WANG Xin, HE Lei, JING Linlin, JIA ZhengPing. Study on myocardium and brain damage in rats by simulating high altitude[J]. Journal of Pharmaceutical Practice and Service, 2018, 36(3): 250-254. doi: 10.3969/j.issn.1006-0111.2018.03.013
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Study on myocardium and brain damage in rats by simulating high altitude

doi: 10.3969/j.issn.1006-0111.2018.03.013
  • 1.

    School of Pharmacy, Lanzhou University, Lanzhou 730000, China;Lanzhou General Hospital Key Lab of PLA for Prevention and Treatment of Injuries induced by High Altitude, Lanzhou 730050, China

  • 2.

    Lanzhou General Hospital Key Lab of PLA for Prevention and Treatment of Injuries induced by High Altitude, Lanzhou 730050, China

  • Received Date: 2017-09-14
  • Rev Recd Date: 2018-01-24
  • 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.
  • [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.
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Study on myocardium and brain damage in rats by simulating high altitude

doi: 10.3969/j.issn.1006-0111.2018.03.013
  • 1. School of Pharmacy, Lanzhou University, Lanzhou 730000, China;Lanzhou General Hospital Key Lab of PLA for Prevention and Treatment of Injuries induced by High Altitude, Lanzhou 730050, China
  • 2. Lanzhou General Hospital Key Lab of PLA for Prevention and Treatment of Injuries induced by High Altitude, Lanzhou 730050, China
  • Received Date: 2017-09-14
  • Rev Recd Date: 2018-01-24

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.

LUO Chuan, LI Jing, ZHANG Wannian, MIAO Zhenyuan. Discovery of bepridil as a valuable lead compound with potent p53-MDM2 inhibitory activity[J]. Journal of Pharmaceutical Practice and Service, 2021, 39(2): 126-129. doi: 10.12206/j.issn.1006-0111.202009031
Citation: WU Ningzi, MA HuiPing, WANG Xin, HE Lei, JING Linlin, JIA ZhengPing. Study on myocardium and brain damage in rats by simulating high altitude[J]. Journal of Pharmaceutical Practice and Service, 2018, 36(3): 250-254. doi: 10.3969/j.issn.1006-0111.2018.03.013
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