目的 采用动物试验研究对香豆酸(p-coumaric acid, p-CA)对急性缺氧性肺水肿的预防作用。方法 建立急性缺氧小鼠模型,以红景天苷为阳性对照,连续灌胃给药7 d,通过检测急性缺氧处理后小鼠肺组织的含水量、炎症因子、抗氧化酶活性和Na+, K+-ATP酶活力,观察苏木素伊红(hematoxylin-eosin,HE)染色切片结果,对p-CA预防急性缺氧性肺水肿的效果及其可能的作用机制进行研究。结果 与正常组相比,急性缺氧(9.5% O2)6 h使小鼠肺组织含水量显著增加了3.56%(P<0.01),而25和100 mg·kg-1·d-1剂量的p-CA均能有效抑制其升高趋势(P<0.05),与红景天苷的效果相当。其作用机制可能与p-CA提高小鼠肺组织Na+,K+-ATP酶活力与抗氧化能力及降低炎症因子水平有关。结论 p-CA对急性缺氧导致的肺水肿具有较好的预防作用。
Abstract
OBJECTIVE To study the preventing effects of p-coumaric acid(p-CA) on acute hypoxia-induced pulmonary edema by mice experiments. METHODS Acute-hypoxia model was established using a normobaric hypoxia chamber in vivo. Salidroside was set as a positive control drug. And the test period was 7 d using a method of intragastric administration. The measurements including pulmonary water content, HE staining, inflammatory factors, anti-oxidative indexes and Na+, K+-ATPase were performed to determine the efficacies and mechanisms of p-CA on preventive against acute hypoxia-induced pulmonary edema. RESULTS As compared with the normal group, pulmonary water contents increased significantly by 3.56% in the mice treated with acute hypoxia (9.5% O2) for 6 h (control group) (P<0.01), and administration with p-CA (25, 100 mg·kg-1·d-1) for 7 d could significantly reduce this index (P<0.05), which was as effective as the positive group. The action mechanisms of p-CA could be due to its abilities of improving the activity of Na+, K+-ATPase, enhancing antioxidant capacity (SOD↑, CAT↑ and MDA↓) and inhibiting inflammatory factors (IL-1β and IL-6). CONCLUSION p-CA has greater preventive effects on acute hypoxia-induced pulmonary edema in mice.
关键词
对香豆酸 /
急性缺氧 /
肺水肿 /
抗氧化 /
炎症因子 /
Na+ /
K+-ATP酶
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Key words
p-coumaric acid /
acute hypoxia /
pulmonary edema /
anti-oxidative /
inflammatory factors /
Na+ /
K+-ATPase
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参考文献
[1] HACKETT P H, RENNIE D, LEVINE H D. Incidence, importance, and prophylaxis of acute mountain-sickness. Lancet, 1976, 2(7996):1149-1155.
[2] HONIGMAN B, THEIS M K, KOZIOLMCLAIN J, et al. Acute mountain-sickness in a general tourist population at moderate altitudes. Ann Intern Med, 1993, 118(8):587-592.
[3] LAHM T, CRISOSTOMO P R, MARKEL T A, et al. Selective estrogen receptor-alpha and estrogen receptor-beta agonists rapidly decrease pulmonary artery vasoconstriction by a nitric oxide-dependent mechanism. Am J Physiol-Reg I, 2008, 295(5):1486-1493.
[4] SWENSON E R, BARTSCH P. High Altitude:Human Adaptation to Hypoxia. Heidelberg:Springer New York Heidelberg Dordrecht London, 2014:405-408.
[5] GRUNIG E, MERELES D, HILDEBRANDT W, et al. Stress Doppler echocardiography for identification of susceptibility to high altitude pulmonary edema. J Am Coll Cardiol, 2000, 35(4):980-987.
[6] SCHOENE R B, SWENSON E R, PIZZO C J, et al. The lung at high altitude: bronchoalveolar lavage in acute mountain sickness and pulmonary edema. J Appl Physiol, 1988, 64(6):2605-2613.
[7] CARPENTER T C, REEVES J T, DURMOWICZ A G. Viral respiratory infection increases susceptibility of young rats to hypoxia-induced pulmonary edema. J Appl Physiol, 1998, 84(3):1048-1054.
[8] BERTHIAUME Y, FOLKESSON H G, MATTHAY M A. Lung edema clearance:20 years of progress-invited review: alveolar edema fluid clearance in the injured lung. J Appl Physiol, 2002, 93(6):2207-2213.
[9] SARADA S, HIMADRI P, MISHRA C, et al. Role of oxidative stress and NFκB in hypoxia-induced pulmonary edema. Exp Biol Med, 2008, 233(9):1088-1098.
[10] CHU B Q, CHEN C, LI J J, et al. Effects of Tibetan turnip (Brassica rapa L.) on promoting hypoxia-tolerance in healthy humans. J Ethnopharmacol, 2017, 195:246-254.
[11] LIU Y F. Study on the anti-hypoxia functional food made from the main components of Tibet Brassica rapa L.. Hangzhou:Zhejiang University, 2012.
[12] CHU B Q. Separation and anti-hypoxia mechanisms of functional compound from Tibetan turnip (Brassica rapa L.) . Hangzhou:Zhejiang University, 2017.
[13] LIU L Y. Acylation of flavone c-g1ycosides and characteristics of oil-soluble antioxidant of bamboo leaves. Hangzhou:Zhejiang University, 2015.
[14] PRAGASAM S J, VENKATESAN V, RASOOL M K. Immunomodulatory and anti-inflammatory effect of p-coumaric acid, a common dietary polyphenol on experimental inflammation in rats. Inflammation, 2013, 36(1):169-176.
[15] JAGANATHAN S K, SUPRIYANTO E, MANDAL M. Events associated with apoptotic effect of p-coumaric acid in HCT-15 colon cancer cells. World J Gastroenterol, 2013, 19(43):7726-7734.
[16] ZHU L P, WEI T T, CHANG X Y, et al. Effects of salidroside on myocardial injury in vivo in vitro via regulation of Nox/NF-kappa B/AP1 pathway. Inflammation, 2015, 38(4):1589-1598.
[17] YAO L J, LIU Y. Protective effects of salidroside on chronic obstructive pulmonary disease in mice. Chin Pharm J (中国药学杂志), 2017, 52(17):1515-1518.
[18] NATH B, SZABO G. Hypoxia and hypoxia inducible factors: diverse roles in liver diseases. Hepatology, 2012, 55(2):622-633.
[19] LI W H. The effects of Rhodiola Tibetica on lung tissue of rats with high altitude pulmonary edema. Adv Mater Res, 2013, 690-693:1305-1309.
[20] LEE S Y, LI M H, SHI L S, et al. Rhodiola crenulata extract alleviates hypoxic pulmonary edema in rats. Evid Based Complement Alternat Med, 2013:718739. doi:10.1155/2013/718739.
[21] YOSHINARI D, TAKEYOSHI I, KOIBUCHI Y, et al. Effects of a dual inhibitor of tumor necrosis factor-alpha and interleukin-1 on lipopolysaccharide-induced lung injury in rats: involvement of the p38 mitogen-activated protein kinase pathway. Crit Care Med, 2001, 29(3):628-634.
[22] LI F S. Study on the anti-hypoxia pharmacological effect and mechanism of total flavonoids of Epimedium Herb. Lanzhou:Lanzhou University, 2009.
[23] HU D Y, LI Q, LI B, et al. Stress response to hypoxia in Wistar rat:LA, MDA, SOD and Na+,K+-ATPase. 3rd International Conference on Bioinformatics & Biomedical Engineering. Beijing:IEEE, 2009:1-5.
[24] ZHANG L. Effect of tetramethylpyrazine on pulmonary edema induced by simulated altitude hypoxia in rats. Chongqing:Army Medical University, 2011.
[25] TAN Y, WEN X S, QI R R, et al. The effects of Portulaca oleracea on hypoxia-induced pulmonary edema in mice. High Alt Med Biol, 2015, 16(1):43-51.
[26] LUKS A M, SWENSON E R. Travel to high altitude with pre-existing lung disease. Eur Respir J, 2007, 29(4):770-792.
[27] CHAKRABORTI S, DHALLA N S, CHAKRABORTI S, et al. Regulation of Membrane Na+,K+-ATPase. Heidelberg:Advances in Biochemistry in Health and Disease, 2016:3, 15 and 123.
[28] SUZUKI S, NODA M, SUGITA M, et al. Impairment of transalveolar fluid transport and lung Na+, K+-ATPase function by hypoxia in rats. J Appl Physiol, 1999, 87(3):962-968.
[29] PAUL S, ARYA A, GANGWAR A, et al. Size restricted silymarin suspension evokes integrated adaptive response against acute hypoxia exposure in rat lung. Free Rad Bio Med, 2016, 96:139-151.
[30] GUZY R D, HOYOS B, ROBIN E, et al. Mitochondrial complex Ⅲ is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab, 2005, 1(6):401-408.
[31] ZEPEDA A B, PESSOA J R A, CASTILLO R L, et al. Cellular and molecular mechanisms in the hypoxic tissue:role of HIF-1 and ROS. Cell Biochem Funct, 2013, 31(6):451-459.
[32] BASTARACHE J A, SEBAG S C, GROVE B S, et al. Interferon-gamma and tumor necrosis factor-alpha act synergistically to up-regulate tissue factor in alveolar epithelial cells. Exp Lung Res, 2011, 37(8):509-517.
[33] ZHOU Q Q, WANG D, LIU Y S, et al. Solnatide demonstrates profound therapeutic activity in a rat model of pulmonary edema induced by acute hypobaric hypoxia and exercise. Chest, 2016, 151(3):658-667.
[34] HUANG X, ZHAO Y Y. Transgenic expression of foxM1 promotes endothelial repair following lung injury induced by polymicrobial sepsis in mice. PLoS One, 2012, 7(e5009411).
[35] SONG T T, BI Y H, GAO Y Q, et al. Systemic pro-inflammatory response facilitates the development of cerebral edema during short hypoxia. J Neuroinflam, 2016, 13:63.
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脚注
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基金
国家自然科学基金面上项目资助(31371754)
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