目的 探究急进4 300 m高原对Wistar大鼠机体血气生化改变、病理变化、血清肿瘤坏死因子-α和白细胞介素-1β影响及醋甲唑胺干预对大鼠高原损伤的保护作用。 方法 将28只成年健康Wistar大鼠按体重随机分为平原(海拔55米)对照组、高原(海拔4 300 m)模型组、醋甲唑胺组、乙酰唑胺组,分别灌胃给予0.9%氯化钠注射液、醋甲唑胺(每日2次,剂量为2.23 mg·kg-1)和乙酰唑胺(每日2次,剂量为22.33 mg·kg-1),对大鼠进行生化、血气分析、病理比较,并检测所得血清样品肿瘤坏死因子-α和白细胞介素-1β含量。 结果 血气、生化和病理结果显示,高原组大鼠出现脱水症状,与平原对照组比较,高原模型组各指标变化显著(P＜0.01),与高原模型组比较,醋甲唑胺组和乙酰唑胺组门冬氨酸转氨酶(AST)、丙氨酸氨基转移酶(ALT)、酸碱度(pH)、碳酸氢根离子浓度、缓冲碱(BB)、剩余碱(BE)等指标显著下降(P＜0.01),总蛋白(TP)、尿素(UREA)、二氧化碳分压(PaCO2)、钠离子浓度、氯离子浓度等指标显著上升(P＜0.01),表明两组均出现代谢性酸中毒合并呼吸性碱中毒,且肝肺组织出现病理性损伤,其中,与乙酰唑胺组比较,醋甲唑胺组损伤较小。与平原对照组相比,高原组血清肿瘤坏死因子-α显著性升高,白细胞介素-1β显著性降低,其中,乙酰唑胺组和醋甲唑胺组血清肿瘤坏死因子-α、白细胞介素-1β含量均显著高于模型组(P＜0.01)。 结论 醋甲唑胺能改善急进高原大鼠的生理生化状况,减轻炎症损伤,具有较好的缺氧保护作用。
Abstract
OBJECTIVE To investigate the effect of acute exposure to 4 300 m altitude environments on the body pathophysiological, serum, TNF-α and IL-1β of Wistar rats and protective effect of methazolamide on Wistar rats. METHODS Twenty-eight Healthy adult Wistar rats were randomly divided into plain(altitude of 55 m) control group, high altitude(altitude of 4 300 m) model group, high altitude methazolamide group, and high altitude acetazolamide group. After being intragastric administration with 0.9% sodium chloride injection, methazolamide(2 times a day, 2.23 mg·kg-1) and acetazolamide(2 times a day, 22.33 mg·kg-1) for 5 consecutive days. The biochemical, blood gas, the pathological results of rats were analyzed. The TNF-α and IL-1β content were detected from the blood samples. RESULTS Blood and biochemical results showed the high altitude might cause dehydration in rats. Compared with the plain control group, each index of the high altitude model group changed significantly(P＜0.01), compared with the high altitude group, the aspartate transaminase(AST), alanine aminotransferase(ALT), pH value, bicarbonate concentration(cHCO3-), buffer base(BB), base excess(BE) of methazolamide and acetazolamide group were significantly decreased(P＜0.01), indicated that methazolamide and acetazolamide had protective effect on rat liver. The total protein(TP), urea solution(UREA), partial pressure of carbon dioxide(PaCO2), sodium concentration(cNa+), chloride concentration(cCl-) were significantly increased(P＜0.01), indicated that the high altitude group had metabolic acidosis and respiratory alkalosis, and liver and lung tissue had pathological damaged. Compared with the acetazolamide group, the methazolamide group damaged less. Compared with plain control group, serum TNF-α of high altitude groups significantly increased, IL-1β of high altitude groups decreased significantly, which, serum TNF-α, IL-1β levels of acetazolamide and methazolamide group were significantly higher than high altitude model group(P<0.01). CONCLUSION Methazolamide can improve acute high altitude physiological and biochemical status of rats, reduce inflammatory injury, with a good protective effect of hypoxia.
关键词
急进高原 /
醋甲唑胺 /
炎症因子 /
血气生化分析
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Key words
acute high altitude /
methazolamide /
inflammatory factor /
blood gas, biochemical analysis
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中图分类号：
R965
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参考文献
[1] SU Y G. Determinants of acute mountain sickness and improvement of hypoxia toleration by the target-based carbonic anhydrase inhibitors Sulzolamide[D]. Beijing: Academy of Military Medical Sciences, 2012: 6-7.
[2] JEFFREY H G, GRANT S L, PETER S H, et al. Prospective, double-blind, randomized, placebo-controlled comparison of acetazolamide versus ibuprofen for prophylaxis against high altitude headache: The headache evaluation at altitude trial(HEAT) [J]. Wild Environ Med, 2010, 21(3): 236-243.
[3] ZHOU S M, WANG R J, ZHANG G, et al. Anti-fatigue function of silkworm pupa protein in simulation plateau-condition mice [J]. Mod Prev Med(现代预防医学杂志), 2012, 39(6): 1497-1501.
[4] LI F X, XU Z X, XIA Q M, et al. Effects of hypoxic acclimatization on HIF-1A expression in rats and the pulmonary structure in rats [J]. Med J West China(西部医学), 2008, 20(4): 689-692.
[5] WANG Z F, DAI B, KANG J. Effects of chronic intermittent hypoxia on rat brain hypoxia inducible factor-1A expression and neuronal apoptosis [J]. Chin J Pathophysiol(中国病理生理学杂志), 2010, 26(3): 593-595.
[6] LI W B,WANG R, XIE H, et al. Effects on the pharmacokinetics of furosemide after acute exposure to high altitude at 4010 meters in rats[J]. Acta Pharm Sin(药学学报), 2012, 47(12): 1718-1721.
[7] LI X Y, LIU Y N, YUAN M, et al. Effect of high altitude hypoxia on the activity and protein expression of CYP2C9 and CYP2C19 [J]. Acta Pharm Sin(药学学报), 2012, 47(3): 188-193.
[8] ZHAO W, SUN G L. Different kinds of animals dosage conversion [J]. Chinese Journal of Animal Husbandry and Veterinary Medicine(畜牧兽医科技信息), 2010,25(5): 52-53.
[9] FAN J, QIN J, LIU C X, et al. Establishment of normal reference range of blood hematological and biochemical indicators of SPF wistar rats [J]. J Pub Heal Prev Med, 2010, 21(6): 50-52.
[10] PARKER D G. Integrated and automatic mixing of whole blood: An evaluation of a novel blood gas analyzer [J]. Clin Chim Acta, 2007, 375(1/2): 153-157.
[11] VENKATESH B, BOOTS R J. Carbon dioxide and oxygen partial pressure measurements in the cerebrospinal fluid in aconventional blood gas analyzer: Analysis of bias and precision [J]. Can J Neurol Sci, 1997, 147(1): 5-8.
[12] LIU R W. Testing and Clinical(临床检验)[M]. Beijing: Chemical Industry Press, 2009:90-160.
[13] SHI Z F, ZHOU Q Q, MA S D, et al. A unit of relief soldiers altitude not adaptation survey[J]. J Prev Med Chin PLA(解放军预防医学杂志), 2011, 29(2): 34-36.
[14] LIU L Y, YANG L F, CAO Y. Latest advances in hypoxia inducible factor-1 signaling pathway [J]. Int J Pathol Clin Med(国际病理科学与临床杂志), 2011, 31(3): 218-222.
[15] MICHAEL K, TOBIAS E, HOLGER K E. The hypoxia-inflammation link and potential drug targets[J]. Curr Opin Anaesthesiol, 2011, 24(4): 363-369.
[16] IMTIYAZ H Z, SIMON M C. Hypoxia-inducible factors as essential regulators of inflammation[J]. Curr Top Microbiol Immunol, 2010, 345: 105-120.
[17] WANG Y W, LAN Y J, YANG Y L, et al. TNF-α and IL-1RA polymorphisms and silicosis susceptibility in Chinese workers exposed to silica particles: A case-control study[J]. Biomed Environ Sci, 2012, 25(5): 517-525.
[18] HIVANA P M, LUISA C M, SIDNEY E B, et al. Interleukin-1 and TNF-α polymorphisms and Helicobacter pylori in a brazilian amazon population[J]. World J Gastroenterol, 2009, 15(12): 1465-1471.
[19] CARSTEN C S, MIGUEL A S, MURTAZA M T, et al. Regulation of IL-1β-induced NF-κB by hydroxylases links key hypoxic and inflammatory signaling pathways[J]. Proc Natl Acad Sci, 2013, 110(46): 18490-18495.
[20] FITZPATRICK S F, TAMBUWALA M M, BRUNING U,et al. An intact canonical NF-kappaB pathway is required for inflammatory gene expression in response to hypoxia [J]. J Immunol, 2011, 186(2): 1091-1097.
[21] LI Z E, WE H, DENG L Z, et al. Expression and secretion of interleukin-1β, tumour necrosis factor-α and interleukin-10 by hypoxia- and serum-deprivation-stimulated mesenchymal stem cells[J]. FEBS J, 2010, 277(18): 3688-3698.
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脚注
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基金
国家科技部重大资助项目(2008ZXJ09014－010);全军医药科研“十二五”重点资助项目(BWS12J012);全军医药科研“十二五”面上项目(CWS11C231)
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