Protective effect of sodium butyrate on hypoxia tolerance in rats exposed to hypoxia and cold

Xiaoyu GUO; Xiaoling TAN; Qi CUI; Hongchen XIE; Yujie HUANG; Xiangqiong MENG; Wenjun JIANG; Yu DING; Haixia JING

doi:10.16016/j.2097-0927.202312056

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Protective effect of sodium butyrate on hypoxia tolerance in rats exposed to hypoxia and cold

Military Medicine | 更新时间：2026-01-09

- Protective effect of sodium butyrate on hypoxia tolerance in rats exposed to hypoxia and cold
- Journal of Army Medical University Vol. 46, Issue 8, Pages: 901-911(2024)
- 作者机构：
  
  1.810016 西宁，青海大学农牧学院动物医学系
  2.400038 重庆，陆军军医大学(第三军医大学)高原军事医学系寒区医学教研室
  3.400038 重庆，陆军军医大学(第三军医大学)极端环境医学教育部重点实验室
- 作者简介：
- 基金信息：
- DOI：10.16016/j.2097-0927.202312056
  CLC： R-332;R339.55;R977.6
- Received：11 December 2023，
  
  Revised：2024-01-17，
  
  Published：30 April 2024
- 稿件说明：
移动端阅览
Xiaoyu GUO, Xiaoling TAN, Qi CUI, et al. Protective effect of sodium butyrate on hypoxia tolerance in rats exposed to hypoxia and cold[J]. Journal of Army Medical University, 2024, 46(8): 901-911.
DOI：

Xiaoyu GUO, Xiaoling TAN, Qi CUI, et al. Protective effect of sodium butyrate on hypoxia tolerance in rats exposed to hypoxia and cold[J]. Journal of Army Medical University, 2024, 46(8): 901-911. DOI： 10.16016/j.2097-0927.202312056.

摘要

目的

探究丁酸钠对低氧寒冷暴露下大鼠的保护作用及其机制。

方法

7~8周、体质量240~260 g雄性SD大鼠随机分为: 常氧常温生理盐水对照(normoxia normothermia saline control

NNC

=10)组、常氧常温丁酸钠(normoxia normothermia sodium butyrate

NNB

=10)组、低氧寒冷生理盐水对照(hypoxia cold saline control

HCC

=19)组和低氧寒冷丁酸钠(hypoxia cold sodium butyrate

HCB

=19)组。NNB、HCB组的灌胃剂量为200 mg/kg

NNC、HCC组的灌胃剂量为5 mL/kg。①连续灌胃7 d后

HCC、HCB组大鼠置于低压低氧舱内模拟海拔5 000 m、温度8℃暴露7 d

取腹主动脉血进行血气、血常规和血清生化指标检测

ELISA测定血清炎症因子和内分泌激素。NNC、NNB组

大鼠在舱外同时喂养

7 d后进行指标检测

评价丁酸对机体的保护效应(

=10)。②监测HCC、HCB组大鼠核心体温

评价丁酸对低氧寒冷暴露大鼠的体热平衡(

=3)。③检测低氧寒冷暴露前后HCC、HCB大鼠的低氧(平原低氧箱

11% O

)运动耐力

评价耐缺氧能力(

=6)。

结果

与NNC组比较

HCC组大鼠动脉血氧饱和度(arterial oxygen saturation

SaO

)、动脉血氧分压(arterial oxygen partial pressure

PaO

)、IL-4、内分泌激素雌二醇(estradiol

)、皮质醇(cortisol

F)、核心体温以及低氧暴露下的运动时长显著降低(

0.05);而红细胞数目(red blood cell

RBC)、血红蛋白浓度(haemoglobin

HGB)、红细胞压积(hematocrit

HCT)、血清心肌钙蛋白(cardiac troponin

CRDAC-T)、尿酸(uric acid

UA)、谷丙转氨酶(alanine aminotransferase

ALT)、总胆固醇(total cholesterol

TCH)和低密度脂蛋白(low-density lipoprotein

LDL)、IL-6以及粒细胞-巨噬细胞集落刺激因子(granulocyte-macrophage colony-stimulating factor

GM-CSF)显著升高

差异具有统计学意义(

0.05)。与HCC组比较

HCB组大鼠动脉SaO

、PaO

、IL-4、E

、F、促肾上皮质激素释放激素(corticotropin releasing hormone

CRH)、促肾上腺皮质激素(adrenocorticotropic hormone

ACTH)显著升高(

0.05)

低氧暴露下的运动时长显著增加(

0.05);而RBC、HGB、HCT、CRDAC-T、UA、ALT、TCH、LDL、IL-6、GM-CSF、游离甲状腺素(free thyroxine

)以及核心体温显著下降

差异具有统计学意义(

0.05)。

结论

丁酸钠对低氧寒冷暴露条件下的大鼠具有保护作用

有利于低氧寒冷的共习服。

Abstract

Objective

To investigate the protective effects and underlying mechanisms of sodium butyrate on rats exposed to hypoxia and cold conditions.

Methods

Fifty-eight male SD rats (aged 7~8 weeks

weighing 240~260 g) were randomly divided into normoxia normothermia saline control (NNC) group (

=10)

normoxia normothermia sodium butyrate (NNB) group (

=10)

hypoxia cold saline control (HCC) group (

=19)

and hypoxia cold sodium butyrate (HCB) group (

=19).The intragastric dose of sodium butyrate was 200 mg/kg for the NNB and HCB groups

while the NNC and H

CC groups were given normal saline of 5 mL/kg.①After continuous intragastric administration for 7 d

the rats in the HCC and HCB groups were placed in a low-pressure hypoxic chamber to simulate an altitude of 5 000 m and exposed to a temperature of 8℃ for 7 d.Subsequently

blood samples were collected from the abdominal aorta for blood gas analysis

blood routine test

and detection for serum biochemical indicators.ELISA was used to determine serum inflammatory cytokines and endocrine hormones.The rats in the NNC and NNB groups (

=10) were fed outside the chamber and underwent the same tests in 7 d later to evaluate the protective effects of sodium butyrate on the body.②Core body temperature monitoring was conducted to assess the impact of sodium butyrate on thermoregulation in rats exposed to hypoxia and cold (

=3).③Hypoxia exercise tolerance of the HCC group and HCB group in a hypoxic chamber (11% O

) was evaluated for their hypoxia resistance (

=6).

Results

Compared to the NNC group

the rats in the HCC group exhibited significant decreases in arterial oxygen saturation (SaO

) and arterial oxygen partial pressure (PaO

)

serum levels of IL-4

estradiol (E

) and cortisol (F)

core temperature

and exercise duration (

0.05)

and had notably increased levels of red blood cell (RBC) count

hemoglobin (HGB)

hematocrit (HCT)

cardiac troponin (CRDAC-T)

uric acid (UA)

alanine aminotransferase (ALT)

total cholesterol (TC)

low-density lipoprotein (LDL)

IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF)(

0.05).Compared to the HCC group

the rats in the HCB group exhibited significant increases in SaO

PaO

IL-4

corticotropin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH)(

0.05)

remarkably longer exercise duration under hypoxic exposure (

0.05)

but decreases in RBC count

serum levels of HGB

HCT

CRDAC-T

ALT

LDL

IL-6

GM-CSF and free thyroxine (FT

)

and core temperature (

0.05).

Conclusion

Sodium butyrate exhibits protective effects on rats exposed to hypoxia and cold conditions

and it is helpful in their adaptation to these hypoxia and cold environments.

关键词

Keywords

references

ALAMIFAR H, SOLTANIAN S, VAZIRZADEH A, et al . Dietary butyric acid improved growth, digestive enzymes activities and humoral immune parameters in Barramundi ( Lates calcarifer )[J ] . Aquac Nutr, 2019: 156-164. DOI: 10.1111/anu.12977..

IMRAN M, AHMED S, DITTA Y A, et al . Effect of microencapsulated butyric acid supplementation on growth performance, ileal digestibility of protein, gut health and immunity in Broilers[J ] . Indian J Anim Res, 2017: 1618-1622. DOI: 10.18805/ijar.b-788.

CHANG G J, LIU X X, MA N N, et al . Dietary addition of sodium butyrate contributes to attenuated feeding-induced hepatocyte apoptosis in dairy goats[J ] . J Agric Food Chem, 2018, 66(38): 9995-10002. DOI: 10.1021/acs.jafc.8b03526.

TAN X L, FENG L, HUANG X Y, et al . Histone deacetylase inhibitors promote eNOS expression in vascular smooth muscle cells and suppress hypoxia-induced cell growth[J ] . J Cell Mol Med, 2017, 21(9): 2022-2035. DOI: 10.1111/jcmm.13122.

向仕权. 丁酸钠抑制缺氧致血管内皮细胞通透性增加及其机制研究[D]. 重庆: 重庆医科大学, 2016.

XIANG S Q. Inhibition of sodium butyrate on the increased permeability of human umbilical vein endothelial cells induced by hypoxia and its mechanism[D]. Chongqing: Chongqing Medical University, 2016.

WANG D, LIU C D, LI H F, et al . LSD1 mediates microbial metabolite butyrate-induced thermogenesis in brown and white adipose tissue[J ] . Metabolism, 2020, 102: 154011. DOI: 10.1016/j.metabol.2019.154011.

CADENA V, TATTERSALL G J. Body temperature regulation during acclimation to cold and hypoxia in rats[J]. J Therm Biol, 2014, 46: 56-64. DOI: 10.1016/j.jtherbio.2014.10.007.

巴桑卓玛, 程美乐, 贾雪莹, 等. 初进高原的汉族与世居藏族血液学指标的比较研究[J]. 西藏大学学报(社会科学版), 2011(6): 26-28, 67. DOI: CNKI:SUN:XZZK.0.2011-02-009.

BASANGZHUOMA, CHENG M L, JIA X Y, et al . Research on Hematological Index between Native Tibetanand Han Chinese first Entered in to the Plateau[J ] . J Tibet Univ, 2011(6): 26-28, 67. DOI: CNKI:SUN:XZZK.0.2011-02-009.

王占刚, 陈秋红. 高原世居藏族青少年最大运动时氧代谢动力学特点[J]. 解放军预防医学杂志, 2000, 18(3): 173-175. DOI: 10.13704/j.cnki.jyyx.2000.03.006.

WANG Z G, CHEN Q H. Dynamic characteristics of oxygen metabolism in Tibetan adolescents living in plateau during maximum exercise[J]. J Prev Med Chin PLA, 2000, 18(3): 173-175. DOI: 10.13704/j.cnki.jyyx.2000.03.006.

王迪. 世居高原青少年中长跑运动员训练方法与手段研究: 基于甘孜体校冬训期的实验研究[D]. 成都: 成都体育学院, 2013.

WANG D. Research on training methods and means of young middle-distance runners living in plateau-based on the experimental research of Ganzi sports school in winter training period[D]. Chengdu: Chengdu Sport University, 2013.

魏燕玲, 王子. 高原大学生与平原大学生体质特征的对比分析[J]. 吉林体育学院学报, 2017, 33(4): 82-88. DOI: 10.13720/j.cnki.22-1286.2017.04.016.

WEI Y L, WANG Z. Comparative analysis of physical characteristics between plateau college students and plain college students[J]. J Jilin Sport Univ, 2017, 33(4): 82-88. DOI: 10.13720/j.cnki.22-1286.2017.04.016.

HE B F, WANG J C, QIAN G S, et al . Analysis of high-altitude de-acclimatization syndrome after exposure to high altitudes: a cluster-randomized controlled trial[J ] . PLoS One, 2013, 8(5): e62072. DOI: 10.1371/journal.pone.0062072.

罗勇军, 马四清. 急性高原反应发病的危险因素相关研究进展[J]. 第三军医大学学报, 2019, 41(8): 723-728. DOI: 10.16016/j.1000-5404.201812013.

LUO Y J, MA S Q. Advances in research of risk factors for acute high-altitude sickness[J]. J Third Mil Med Univ, 2019, 41(8): 723-728. DOI: 10.16016/j.1000-5404.201812013.

YU J J, NON A L, HEINRICH E C, et al . Time domains of hypoxia responses and-omics insights[J ] . Front Physiol, 2022, 13: 885295. DOI: 10.3389/fphys.2022.885295.

格日力. 高原医学[M]. 北京: 北京大学医学出版社, 2020: 55-65.

GERILI. High altitude medicine[M]. 2nd Ed. Beijing: Peking University Press, 2020: 55-65.

ZHANG X J, XIE W W, DU W R, et al . Consistent differences in brain structure and functional connectivity in high-altitude native Tibetans and immigrants[J ] . Brain Imaging Behav, 2023, 17(3): 271-281. DOI: 10.1007/s11682-023-00759-5.

CHO J I, BASNYAT B, JEONG C, et al . Ethnically Tibetan women in Nepal with low hemoglobin concentration have better reproductive outcomes[J ] . Evol Med Public Health, 2017, 2017(1): 82-96. DOI: 10.1093/emph/eox008.

BEALL C M. Two routes to functional adaptation: Tibetan and Andean high-altitude natives[J]. Proc Natl Acad Sci U S A, 2007, 104(Suppl 1): 8655-8660. DOI: 10.1073/pnas.0701985104.

张迎春. 雌激素临床应用新进展[J]. 中外医学研究, 2018, 16(18): 181-183. DOI: 10.14033/j.cnki.cfmr.2018.18.084.

ZHANG Y C. New progress in clinical application of estrogen[J]. Chin Foreign Med Res, 2018, 16(18): 181-183. DOI: 10.14033/j.cnki.cfmr.2018.18.084.

DAANEN H A M, VAN MARKEN LICHTENBELT W D. Human whole body cold adaptation[J]. Temperature, 2016, 3(1): 104-118. DOI: 10.1080/23328940.2015.1135688.

SPEAKMAN J R, CHI Q S, OȽDAKOWSKI Ƚ, et al . Surviving winter on the Qinghai-Tibetan Plateau: Pikas suppress energy demands and exploit yak feces to survive winter[J ] . Proc Natl Acad Sci U S A, 2021, 118(30): e2100707118. DOI: 10.1073/pnas.2100707118.

格日力. 高原适应的生物基础[M]. 北京: 北京大学医学出版社, 2021: 79.

GERILI. The biological basis of high altitude aduptation[M]. Beijing: Peking University Press, 2021: 79.

SEO Y, GERHART H D, VAUGHAN J, et al . Does acute normobaric hypoxia induce anapyrexia in adult humans?[J ] . High A lt Med Biol, 2017, 18(2): 185-190. DOI: 10.1089/ham.2016.0139.

马兰, 杨应忠, 格日力. 藏羚羊骨骼肌肌红蛋白含量及乳酸脱氢酶、苹果酸脱氢酶活力的研究[J]. 中国应用生理学杂志, 2012, 28(2): 118-121. DOI: 10.13459/j.cnki.cjap.2012.02.001.

MA L, YANG Y Z, GERILI. Study on the content of myoglobin and the activity of lactate dehydrogenase and malate dehydrogenase in skeletal muscle of Tibetan antelope[J]. Chin J Appl Physiol, 2012, 28(2): 118-121. DOI: 10.13459/j.cnki.cjap.2012.02.001.

张雪峰, 杨应忠, 裴志伟, 等. 藏羚羊和藏系绵羊血液内分泌激素水平的比较研究[J]. 生理学报, 2011, 63(4): 342-346. DOI: 10.13294/j.aps.2011.04.001.

ZHANG X F, YANG Y Z, PEI Z W, et al . Comparisons of endocrine hormones levels between Tibetan antelope and Tibetan sheep[J ] . Acta Physiol Sin, 2011, 63(4): 342-346. DOI: 10.13294/j.aps.2011.04.001.

史喜德, 周世强, 刘峰舟, 等. 高原低氧习服的研究进展[J]. 中国现代医学杂志, 2022, 32(24): 40-49. DOI: 10.3969/j.issn.1005-8982.2022.24.007.

SHI X D, ZHOU S Q, LIU F Z, et al . Research progress on acclimatization to high-altitude hypoxia[J ] . China J Mod Med, 2022, 32(24): 40-49. DOI: 10.3969/j.issn.1005-8982.2022.24.007.

熊艳蕾, 彭毛加措, 陈楠, 等. 南极冰穹A低氧复合寒冷环境对考察队员儿茶酚胺含量和心肌酶的影响[J]. 极地研究, 2016, 28(3): 311-316. DOI: 10.13679/j.jdyj.2016.3.311.

XIONG Y L, PENGMAOJIACUO, CHEN N, et al . Effects of Antarctic dome a hypoxia and an extreme cold environment on catecholamines and myocardial enzymes of Chinese expeditioners[J ] . Chin J Polar Res, 2016, 28(3): 311-316. DOI: 10.13679/j.jdyj.2016.3.311.

TEMPLEMAN N M, BEAUDRY J L, LE MOINE C M, et al . Chronic hypoxia- and cold-induced changes in cardiac enzyme and gene expression in CD-1 mice[J ] . Biochim Biophys Acta, 2010, 1800(12): 1248-1255. DOI: 10.1016/j.bbagen.2010.08.004.

CHEN M, YAN S D, CHAI H, et al . Cardiac troponin Ⅰ reduces hypoxia/reoxygenation-induced myocardial cell injury in vitro [J ] . Int J Cardiol, 2012, 158(1): 120-122. DOI: 10.1016/j.ijcard.2012.04.055..

王延玲, 王荣, 杨锁泉, 等. 急进不同低海拔环境对大鼠心肌的影响[J]. 南方医科大学学报, 2014, 34(3): 312-316. DOI: 10.3969/j.issn.1673-4254.2014.03.05.

WANG Y L, WANG R, YANG S Q, et al . Myocardial injury in rats following a sudden increase of altitudes[J ] . J South Med Univ, 2014, 34(3): 312-316. DOI: 10.3969/j.issn.1673-4254.2014.03.05.

熊海涛. 丁酸钠对仔猪抗大肠杆菌感染的作用及其机制研究[D]. 杭州: 浙江大学, 2016.

XIONG H T. Effects and mechannism of butyrate on disease resistant in piglets[D]. Hangzhou: Zhejiang University, 2016.

叶凯丽, 黄诗琴, 胡婷, 等. 丁酸盐对糖尿病肾病小鼠肾损伤的保护作用及机制[J]. 温州医科大学学报, 2023, 53(1): 42-48. DOI: 10.3969/j.issn.2095-9400.2023.01.007.

YE K L, HUANG S Q, HU T, et al . Protective effect of butyrate on renal injury in diabetic nephropathy mice and its mechanism[J ] . J Wenzhou Med Univ, 2023, 53(1): 42-48. DOI: 10.3969/j.issn.2095-9400.2023.01.007.

ZHOU D, PAN Q, XIN F Z, et al . Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier[J ] . World J Gastroenterol, 2017, 23(1): 60-75. DOI: 10.3748/wjg.v23.i1.60.

STILLING R M, VAN DE WOUW M, CLARKE G, et al . The neuropharmacology of butyrate: the bread and butter of the microbiota-gut-brain axis?[J ] . Neurochem Int, 2016, 99: 110-132. DOI: 10.1016/j.neuint.2016.06.011.

PHAM K, PARIKH K, HEINRICH E C. Hypoxia and inflammation: insights from high-altitude physiology[J]. Front Physiol, 2021, 12: 676782. DOI: 10.3389/fphys.2021.676782.

宋园园, 肖英平, 马灵燕, 等. 丁酸梭菌预处理对葡聚糖硫酸钠诱导的结肠炎小鼠肝脏损伤的影响[J]. 动物营养学报, 2023, 35(8): 5384-5395. DOI: 10.12418/CJAN2023.496.

SONG Y Y, XIAO Y P, MA L Y, et al . Effects of Clostridium butyricum pretreatment on liver injury in mice with dextran sulphate sodium-induced colitis[J ] . Chin J Anim Nutr, 2023, 35(8): 5384-5395. DOI: 10.12418/CJAN2023.496..

ZHOU Z Y, PACKIALAKSHMI B, MAKKAR S K, et al . Effect of butyrate on immune response of a chicken macrophage cell line[J ] . Vet Immunol Immunopathol, 2014, 162(1/2): 24-32. DOI: 10.1016/j.vetimm.2014.09.002.

张玉妮, 张兴道, 贺雨, 等. 丁酸钠对坏死性小肠结肠炎小鼠脑损伤的保护作用[J]. 陆军军医大学学报, 2023, 9(13): 1388-1396. DOI: 10.16016/j.2097-0927.202211032.

ZHANG Y N, ZHANG X D, HE Y, et al . Protective effect of sodium butyrate on brain injury in mice with necrotizing enterocolitis[J ] . J Army Med Univ, 2023, 9(13): 1388-1396. DOI: 10.16016/j.2097-0927.202211032.

代忠明, 张伟平, 聂占国. 高原高寒环境对大鼠胃黏膜损伤的影响及IL-4参与作用研究[J]. 西北国防医学杂志, 2015, 36(12): 810-812. DOI: 10.16021/j.cnki.1007-8622.2015.12.014.

DAI Z M, ZHANG W P, NIE Z G. Contributory roles of IL-4 in gastric mucosal injury of rats under cold plateau environment[J]. Med J Natl Defending Forces Northwest China, 2015, 36(12): 810-812. DOI: 10.16021/j.cnki.1007-8622.2015.12.014.

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.

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.

张帅, 李少华, 师启鑫, 等. 间断短时供氧的时长与高度对其防护低压低氧大鼠肺动脉高压作用的影响[J]. 空军军医大学学报, 2023, 44(1): 13-17, 22. DOI: 10.13276/j.issn.2097-1656.2023.01.003.

ZHANG S, LI S H, SHI Q X, et al . Effects of the duration and physiological equivalent altitude of intermittent short-time oxygen supply on its protective effect against pulmonary hypertension in rats with hypobaric hypoxia[J ] . J AirForce Med Univ, 2023, 44(1): 13-17, 22. DOI: 10.13276/j.issn.2097-1656.2023.01.003.

SAVALE L, TU L, RIDEAU D, et al . Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice[J ] . Respir Res, 2009, 10(1): 6. DOI: 10.1186/1465-9921-10-6.

BENDALL L J, BRADSTOCK K F. G-CSF: from granulopoietic stimulant to bone marrow stem cell mobilizing agent[J]. Cytokine Growth Factor Rev, 2014, 25(4): 355-367. DOI: 10.1016/j.cytogfr.2014.07.011.

DOIG C, COOKE R, CHUA C, et al . Acute respiratory distress syndrome precipitated by granulocyte colony-stimulating factor in undiagnosed Pneumocystis jirovecii pneumonia[J ] . BMJ Case Rep, 2022, 15(2): e242316. DOI: 10.1136/bcr-2021-242316..

MERTENS J, LAGHRIB Y, KENYON C. A case of steroid-responsive, COVID-19 immune reconstitution inflammatory syndrome following the use of granulocyte colony-stimulating factor[J]. Open Forum Infect Dis, 2020, 7(8): ofaa326. DOI: 10.1093/ofid/ofaa326.

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Key Laboratory of Extreme Environmental Medicine of Ministry of Education, School of Nursing， Army Medical University （Third Military Medical University）

Department of Frigid Zone Medicine， College of High Altitude Military Medicine, School of Nursing， Army Medical University （Third Military Medical University）

Department of Anesthesiology Children’s Hospital of Chongqing Medical University， National Clinical Research Center for Child Health and Disorders， Ministry of Education Key Laboratory of Child Development and Disorders， Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders

Department of Pathophysiology， Key Laboratory of High Altitude Medicine， Key Laboratory of Extreme Environmental Medicine of Ministry of Education， Faculty of High Altitude Military Medicine， Army Medical University （Third Military Medical University）

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