[1]柯贤锋,何根林,董华平,等.热习服对大鼠高原脑水肿的预防效应及其机制研究[J].第三军医大学学报,2019,41(21):2043-2050.
 KE Xianfeng,,et al.Preventive effects and mechanism of heat acclimation on high altitude cerebral edema in rats[J].J Third Mil Med Univ,2019,41(21):2043-2050.
点击复制

热习服对大鼠高原脑水肿的预防效应及其机制研究(/HTML )
分享到:

《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
41卷
期数:
2019年第21期
页码:
2043-2050
栏目:
基础医学
出版日期:
2019-11-15

文章信息/Info

Title:
Preventive effects and mechanism of heat acclimation on high altitude cerebral edema in rats
作者:
柯贤锋123何根林4董华平123吴刚123徐刚123张二龙123陈建123孙滨达123杨学森4高钰琪123
400038 重庆,陆军军医大学(第三军医大学):高原军事医学系高原特需药品与器材研究室1,极端环境医学教育部重点实验室2,全军高原医学重点实验室3,军事预防医学系热带医学教研室4
Author(s):
KE Xianfeng1 2 3 HE Genlin4 DONG Huaping1 2 3 WU Gang1 2 3 XU Gang1 2 3 ZHANG Erlong1 2 3 CHEN Jian1 2 3 SUN Binda1 2 3 YANG Xuesen4 GAO Yuqi1 2 3

1Department of Medicine and Equipment for High Altitude Region, 2Key Laboratory of Extreme Environmental Medicine of Ministry of Education, 3Key Laboratory of High Altitude Medicine, Faculty of High Altitude Military Medicine, 4Department of Tropical Medicine, Faculty of Military Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, China

关键词:
热习服高原脑水肿预防
Keywords:
heat acclimation high altitude cerebral edema prevention
分类号:
R339.52; R594.301; R742.7
文献标志码:
A
摘要:

目的探讨热习服对大鼠高原脑水肿的预防效应及其机制。方法雄性成年SD大鼠按随机数字表法分为正常对照(C)组、热习服(HA)组(34 ℃,30 d)、缺氧(H)组(7 600 m,1 d)、热习服+缺氧(HHA)组(34 ℃ 30 d+7 600 m 1 d)。各组处理结束后,取脑组织比较其湿干质量比,对脑组织HE染色、FJB染色后观察病理形态学改变,透射电镜观察脑组织超微结构改变,取血液标本检测血常规、血气分析和血红蛋白氧解离曲线,同时检测脑组织中丙二醛(MDA)含量和热休克蛋白70(HSP70)及水通道蛋白4(AQP4)蛋白的表达。结果与C组(4.50±0.07)相比,H组脑组织湿干质量比(4.62±0.08)显著升高(P<0.05);HHA组脑组织湿干质量比(4.52±0.06)显著低于H组(P<0.05)。与C组相比,H组脑组织HE染色和透射电镜结果显示细胞肿胀,胞质疏松,染色质分布不均匀,核明显固缩、破裂、溶解,细胞空泡化明显,FJB染色提示神经元变性增多;与H组相比,HHA组细胞损伤、神经元变性和凋亡程度显著改善。与C组相比,H组血红蛋白、红细胞计数、红细胞压积和中性粒细胞百分比显著升高,血氧饱和度、血氧分压显著降低(P<0.05);与H组相比,HHA组血红蛋白、红细胞和红细胞压积进一步升高,但中性粒细胞百分比显著降低,血氧饱和度、血氧分压显著升高(P<0.05)。与C组相比,H组氧解离曲线发生右移;与H组相比,HHA组氧解离曲线发生右移。与C组相比,H组脑组织MDA含量和AQP4蛋白表达显著升高(P<0.05);与H组相比,HHA组MDA含量和AQP4蛋白表达显著降低,HSP70蛋白表达显著升高(P<0.05)。结论热习服可以有效预防大鼠高原脑水肿的发生,其机制与提高氧气供应、减轻氧化应激、改善细胞损伤等有关。
 

Abstract:

ObjectiveTo investigate the effects and mechanism of heat acclimation (HA) on rats with high altitude cerebral edema. MethodsAdult male SD rats were randomly divided into normal control group (C group), hypoxia group (H group, 7 600 m, 1 d), HA group (34 ℃, 30 d) and hypoxia+HA group (HHA group). All rats were sacrificed after the treatment, and then brain water content, pathological changes (HE staining), neuronal degeneration (Fluoro-Jade B staining) and ultrastructure changes (transmission electron microscopy) were measured and observed. Blood samples were harvested to make blood routine test, blood gas and oxygen dissociation curves. The content of MDA and protein levels of HSP70 and AQP4 in brain tissues were detected. ResultsCompared with group C (4.50±0.07), the wet to dry weight ratio of brain tissue was significantly increased in group H (4.62±0.08, P<0.05), meanwhile, that in the HHA group (4.52±0.06) was significantly lower than that of the H group (P<0.05). In pathological observation, swollen cells, rarefaction cytoplasm, uneven distribution of chromatin and nuclear pyknosis, rupture, dissolved, obvious vacuolation, and aggravated neuronal degeneration were seen in the group H. While in the HHA group, the injury, apoptosis and neuronal degeneration were attenuated. When compared with the values in the group C, hemoglobin level, erythrocyte count, hematocrit, and neutrophil percentage were significantly increased (P<0.05), and SaO2 and PaO2 was significantly reduced (P<0.05) in group H. HHA group had further increased hemoglobin level, erythrocyte count and hematocrit (P<0.05), decreased percentage of neutrophils, and reduced SaO2 and PaO2 in comparison with group H (P<0.05). Oxygen dissociation curve was shifted to right in the group H compared with group C, and that of the HHA group was further shifted right than that of the group H. In addition, compared with group C, MDA content and AQP4 protein level were significantly increased in group H (P<0.05), and in group HHA, those were further decreased (P<0.05), while HSP70 protein was significantly increased (P<0.05). ConclusionHA exerts effective protection on brain edema caused by hypoxia in rats, which may due to its increasing oxygen supply, reducing oxidative stress, and improve cell damage.

参考文献/References:

[1]WEST J B. High-altitude medicine[J]. Am J Respir Crit Care Med, 2012, 186(12): 1229-1237. DOI:10.1164/rccm.201207-1323ci.
[2]HOROWITZ M. Heat acclimation-mediated cross-tolerance: origins in within-life epigenetics?[J]. Front Physiol, 2017, 8: 548. DOI:10.3389/fphys.2017.00548.
[3]YACOBI A, STERN BACH Y, HOROWITZ M. The protective effect of heat acclimation from hypoxic damage in the brain involves changes in the expression of glutamate receptors[J]. Temperature (Austin), 2014, 1(1): 57-65. DOI:10.4161/temp.29719.
[4]SARADA S K, TITTO M, HIMADRI P, et al. Curcumin prophylaxis mitigates the incidence of hypobaric hypoxia-induced altered ion channels expression and impaired tight junction proteins integrity in rat brain[J]. J Neuroinflammation, 2015, 12: 113. DOI:10.1186/s12974-015-0326-4.
[5]GONG G, YIN L, YUAN L B, et al. Ganglioside GM1 protects against high altitude cerebral edema in rats by suppressing the oxidative stress and inflammatory response via the PI3K/AKT-Nrf2 pathway[J]. Mol Immunol, 2018, 95: 91-98. DOI:10.1016/j.molimm.2018.02.001.
[6]PRIARD J D, RACINAIS S, SAWKA M N. Adaptations and mechanisms of human heat acclimation: Applications for competitive athletes and sports[J]. Scand J Med Sci Sports, 2015, 25(Suppl 1): 20-38. DOI:10.1111/sms.12408.
[7]HOROWITZ M. Epigenetics and cytoprotection with heat acclimation[J]. J Appl Physiol, 2016, 120(6): 702-710. DOI:10.1152/japplphysiol.00552.2015.
[8]GIBSON O R, TAYLOR L, WATT P W, et al. Cross-adaptation: heat and cold adaptation to improve physiological and cellular responses to hypoxia[J]. Sports Med, 2017, 47(9): 1751-1768. DOI:10.1007/s40279-017-0717-z.
[9]UMSCHWEIF G, SHEIN N A, ALEXANDROVICH A G, et al. Heat acclimation provides sustained improvement in functional recovery and attenuates apoptosis after traumatic brain injury[J]. J Cereb Blood Flow Metab, 2015, 35(11): 1901. DOI:10.1038/jcbfm.2015.207.
[10]官立彬, 李晓栩, 李锦松, 等. 5-羟甲基糠醛对模拟高原大鼠血红蛋白氧结合特性及游泳耐力和空间记忆能力的影响[J]. 第三军医大学学报, 2015, 37(15): 1561-1565. DOI:10.16016/j.1000-5404.201411147.
GUAN L B, LI X X, LI J S, et al. Effect of 5-HMF on hemoglobin-oxygen affinity, swimming endurance and spatial memory ability of rats in high altitude simulated environment[J]. J Third Mil Med Univ, 2015, 37(15): 1561-1565. DOI:10.16016/j.1000-5404.201411147.
[11]ELLIS S S, PEPPLE D J. Sildenafil increases the p50 and shifts the oxygen-hemoglobin dissociation curve to the right[J]. J Sex Med, 2015, 12(12): 2229-2232. DOI:10.1111/jsm.13038.
[12]LORENZO S, HALLIWILL J R, SAWKA M N, et al. Heat acclimation improves exercise performance[J]. J Appl Physiol, 2010, 109(4): 1140-1147. DOI:10.1152/japplphysiol.00495.2010.
[13]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]. J Neuroinflammation, 2016, 13(1): 63. DOI:10.1186/s12974-016-0528-4.
[14]ZHOU Y Z, HUANG X, ZHAO T, et al. Hypoxia augments LPS-induced inflammation and triggers high altitude cerebral edema in mice[J]. Brain Behav Immun, 2017, 64: 266-275. DOI:10.1016/j.bbi.2017.04.013.
[15]HIMADRI P, KUMARI S S, CHITHARANJAN M, et al. Role of oxidative stress and inflammation in hypoxia-induced cerebral edema: a molecular approach[J]. High Alt Med Biol, 2010, 11(3): 231-244. DOI:10.1089/ham.2009.1057.
[16]SHEIN N A, DORON H, HOROWITZ M, et al. Altered cytokine expression and sustained hypothermia following traumatic brain injury in heat acclimated mice[J]. Brain Res, 2007, 1185: 313-320. DOI:10.1016/j.brainres.2007.09.024.
[17]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. DOI:10.1016/j.freeradbiomed.2013.05.024.
[18]EYNAN M, ERTRACHT O, GANCZ H, et al. Prolonged latency to CNS-O2 toxicity induced by heat acclimation in rats is associated with increased antioxidative defenses and metabolic energy preservation[J]. J Appl Physiol, 2012, 113(4): 595-601. DOI:10.1152/japplphysiol.00228.2012.
[19]KIM J Y, HAN Y, LEE J E, et al. The 70-kDa heat shock protein (Hsp70) as a therapeutic target for stroke[J]. Expert Opin Ther Targets, 2018, 22(3): 191-199. DOI:10.1080/14728222.2018.1439477.
[20]LIN H, CHANG C P, LIN H J, et al. Attenuating brain edema, hippocampal oxidative stress, and cognitive dysfunction in rats using hyperbaric oxygen preconditioning during simulated high-altitude exposure[J]. J Trauma Acute Care Surg, 2012, 72(5): 1220-1227. DOI:10.1097/TA.0b013e318246ee70.
[21]WU H H, NIU K C, LIN C H, et al. HSP-70-mediated hyperbaric oxygen reduces brain and pulmonary edema and cognitive deficits in rats in a simulated high-altitude exposure[J]. Biomed Res Int, 2018, 2018: 4608150. DOI:10.1155/2018/4608150.
[22]MANLEY G T, FUJIMURA M, MA T, et al. Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke[J]. Nat Med, 2000, 6(2): 159-163. DOI:10.1038/72256.
[23]WANG C, YAN M Y, JIANG H, et al. Mechanism of aquaporin 4 (AQP 4) up-regulation in rat cerebral edema under hypobaric hypoxia and the preventative effect of puerarin[J]. Life Sci, 2018, 193: 270-281. DOI:10.1016/j.lfs.2017.10.021.

相似文献/References:

[1]杨卫波,李素芝,高钰琪,等.急性肾功能损伤在急性高原病发病过程中的差异研究[J].第三军医大学学报,2018,40(12):1109.
 YANG Weibo,LI Suzhi,GAO Yuqi,et al.Phenotypes of acute renal function injuries in different acute high-altitude diseases[J].J Third Mil Med Univ,2018,40(21):1109.

更新日期/Last Update: 2019-11-12