矮垂头菊正丁醇提取物对低压低氧小鼠心肌损伤的保护作用

谭宏强; 张洁; 张朋朋; 石志群; 马慧萍; 景临林; 张汝学

doi:10.16016/j.2097-0927.202212105

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矮垂头菊正丁醇提取物对低压低氧小鼠心肌损伤的保护作用

药学 | 更新时间：2026-01-09

- 矮垂头菊正丁醇提取物对低压低氧小鼠心肌损伤的保护作用
- Protective effect of n-butanol extract of Cremanthodium humile on myocardial injury induced by hypobaric hypoxia in mice
- 陆军军医大学学报 2023年45卷第14期页码：1493-1500
- 作者机构：
  
  1.730000 兰州，甘肃中医药大学药学院
  2.730050 兰州，中国人民解放军联勤保障部队第九四○医院药剂科
  3.710061 西安，西安交通大学医学院第一附属医院药学部
- 作者简介：
  
  [张汝学，E-mail：ruxuezh@126.com ZHANG Ruxue, E-mail: ruxuezh@126.com
- 基金信息：
  
  国家自然科学基金面上项目(81872796)
- DOI：10.16016/j.2097-0927.202212105
  中图分类号： R285.5;R339.5;R542.2
- 收稿：2022-12-16，
  
  修回：2023-02-11，
  
  纸质出版：2023-07-30
- 稿件说明：
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谭宏强, 张洁, 张朋朋, 等. 矮垂头菊正丁醇提取物对低压低氧小鼠心肌损伤的保护作用[J]. 陆军军医大学学报, 2023,45(14):1493-1500.

Hongqiang TAN, Jie ZHANG, Pengpeng ZHANG, et al. Protective effect of n-butanol extract of Cremanthodium humile on myocardial injury induced by hypobaric hypoxia in mice[J]. Journal of Army Medical University, 2023, 45(14): 1493-1500.
谭宏强, 张洁, 张朋朋, 等. 矮垂头菊正丁醇提取物对低压低氧小鼠心肌损伤的保护作用[J]. 陆军军医大学学报, 2023,45(14):1493-1500. DOI： 10.16016/j.2097-0927.202212105.

Hongqiang TAN, Jie ZHANG, Pengpeng ZHANG, et al. Protective effect of n-butanol extract of Cremanthodium humile on myocardial injury induced by hypobaric hypoxia in mice[J]. Journal of Army Medical University, 2023, 45(14): 1493-1500. DOI： 10.16016/j.2097-0927.202212105.

摘要

目的

研究矮垂头菊正丁醇提取物(n-butanol extract of

Cremanthodium humile

，BECH)对低压低氧小鼠心肌损伤的保护作用。

方法

取清洁级BALB/c雄性小鼠50只分为(

=10)：缺氧模型组、乙酰唑胺组，BECH低(125 mg/kg)、中(250 mg/kg)、高剂量(500 mg/kg)组进行常压密闭缺氧实验确定最佳给药剂量。30只小鼠分为(

=10)：急性减压组、乙酰唑胺组、BECH给药组进行减压缺氧耐受实验确定最佳给药剂量的存活率。52只小鼠分为(

=13)：正常对照组、低压低氧组、乙酰唑胺组和BECH给药组，连续灌胃5 d，第5天给药后，正常对照组置于当地海拔，其余小鼠置于低压低氧动物实验舱中。模拟海拔高度8 000 m暴露24 h，摘眼球取血后随即处死，HE染色观察小鼠心肌组织病理变化；测定血清中肌酸激酶(creatine kinase，CK)、谷草转氨酶(aspartate aminotransferase，AST)、心肌肌钙蛋白I(cardiac troponin I，c-TnI)活性；测定心肌组织中活性氧(reactive oxygen species，ROS)、过氧化氢酶(catalase，CAT)、丙二醛(malondialdehyde，MDA)、超氧化物歧化酶(superoxide dismutase，SOD)、乳酸(lactic acid，LD)、乳酸脱氢酶(lactate dehydrogenase，LDH)、谷胱甘肽过氧化物酶(glutathione peroxidase，GSH-Px)和总抗氧化能力(total antioxidant capacity，T-AOC)含量和水平；蛋白印迹法检测心肌组织中Nrf-2、HO-1、Bax、Bcl-2、cleaved Caspase-3蛋白的表达水平。

结果

与缺氧模型组相比，BECH可以显著延长常压密闭缺氧小鼠的存活时间，且以高剂量组效果较好；与急性减压组相比，BECH给药组能够显著降低急性减压小鼠的死亡率。与正常对照组相比，低压低氧组小鼠心肌组织中ROS含量升高(

0.05)，MDA、CAT、LD、LDH的水平显著增加(

0.01)，SOD、GSH-Px、T-AOC的水平显著降低(

0.01)，Nrf-2、HO-1、Bax、cleaved Caspase-3蛋白表达上调(

0.05，

0.01)，Bcl-2蛋白表达下调(

0.05)。经BECH治疗后，能够显著降低低压低氧环境下小鼠的心肌组织氧化应激损伤(

0.01)，显著降低LD的含量与LDH活性(

0.01)，显著提高SOD、GSH-Px、T-AOC、LDH的水平(

0.01)，上调Bcl-2、Nrf-2、HO-1的蛋白表达水平(

0.05，

0.01)，下调Bax和cleaved Caspase-3蛋白表达(

0.05，

0.01)，降低Bax/Bcl-2比值(

0.05)。

结论

BECH通过激活Nrf-2/HO-1信号通路，降低低压低氧小鼠心肌组织的氧化应激损伤，改善能量代谢，抑制细胞凋亡，进而缓解低压低氧诱导的心肌损伤。

Abstract

Objective

To determine the protective effect of n-butanol extract of

Cremanthodium humile

(BECH) on myo

cardial damage induced by hypobaric hypoxia (HH) in mice.

Methods

Fifty clean-grade BALB/c male mice were divided into (

=10): hypoxia model group

acetazolamide group

low-

medium-and high-dose BECH groups (125

250 and 500 mg/kg) for normobaric confinement hypoxia experiments to determine the optimal dose of administration. Another 30 mice were divided into (

=10): acute decompression group

acetazolamide group and BECH administration group for the survival rate of the best administered dose in decompression hypoxia tolerance experiment. Fifty-two mice were divided into (

=13) normal control group

HH group

acetazolamide group and BECH administration group. BECH or acetazolamide was given intragastrically (i.g.) for 5 consecutive days

then the mice of the normal control group was placed at the local altitude

and those in the other groups were exposed to a simulated altitude of 8 000 m for 24 h in a hypobaric hypoxia chamber. After blood samples were harvested from the eyeball

all mice were sacrificed immediately. Histopathological changes in mouse myocardium were observed with HE staining. The serum activities of CK

AST and c-TnI were determined. The contents and levels of ROS

CAT

MDA

SOD

LDH

GSH-Px and T-AOC in myocardial tissue were measured. Western blotting was used to detect the expression of Nrf-2

HO-1

Bax

Bcl-2 and cleaved Caspase-3 proteins in myocardial tissues.

Results

Compared with the hypoxia model group

BECH treatment significantly prolonged the survival time of mice in normobaric confinement hypoxia

especially the high-dose administration; the treatment also significantly reduced the mortality of mice in acute decompression. Significantly increased levels of ROS (

0.05) and MDA

CAT

LD and LDH (

0.01)

decreased levels of SOD

GSH-Px and T-AOC(

0.01)

up-regulation of Nrf-2

HO-1

Bax and cleaved C

aspase-3 (

0.05

0.01) and down-regulation of Bcl-2 (

0.05) in the myocardial tissues were observed in the mice from the HH model group than those in the control group. While

BECH treatment significantly attenuated myocardial tissue oxidative stress damage in mice under hypobaric hypoxic environment (

0.01)

decreased the amount of LD and the activity of LDH (

0.01)

increased the levels of SOD

GSH-Px and T-AOC(

0.01)

up-regulated the protein levels of Nrf-2

HO-1 amd Bcl-2(

0.05

0.01)

down-regulated those of Bax and cleaved Caspase-3 (

0.05

0.01)

and reduced the Bax/Bcl-2 ratio in myocardial tissue.

Conclusion

BECH inhibits oxidative stress

improves energy metabolism

suppresses cell apoptosis

via

activating the Nrf-2/HO-1 signaling pathway

and then ameliorates HH-induced myocardial tissue injury.

关键词

Keywords

references

张侃, 陈景元, 李维国, 等. 高原高寒地区卫勤保障实践与思考[J]. 西北国防医学杂志, 2014, 35(5): 497-499. DOI: 10.16021/j.cnki.1007-8622.2014.05.097.

ZHANG K, CHEN J Y, LI W G, et al . Practice and thinking of medical support in plateau and cold area[J ] . Med J Natl Defending Forces Northwest China, 2014, 35(5): 497-499. DOI: 10.16021/j.cnki.1007-8622.2014.05.097.

CHEN K, WANG S, SUN Z J. In vivo cardiac-specific expression of Adenylyl cyclase 4 gene protects against klotho deficiency-induced heart failure[J ] . Transl Res, 2022, 244: 101 -113. DOI: 10.1016/j.trsl.2022.01.006..

范宗静, 李星星, 崔杰, 等. 黄芪多糖对缺氧/复氧人心脏微血管内皮细胞凋亡、细胞周期的影响[J]. 中国医学前沿杂志(电子版), 2021, 13(11): 56-60. DOI: 10.12037/YXQY.2021.11-02.

FAN Z J, LI X X, CUI J, et al . Effects of astragalus polysaccharide on apoptosis and cell cycle of human cardiac microvascular endothelial cell injured by hypoxia/reoxygenation[J ] . Chin J Front Med Sci (Electron Version), 2021, 13(11): 56-60. DOI: 10.12037/YXQY.2021.11-02.

景临林, 马慧萍, 樊鹏程, 等. 矮垂头菊乙醇提取物的体外自由基清除活性及其对高原缺氧小鼠的保护作用研究[J]. 天然产物研究与开发, 2015, 27(10): 1815-1820. DOI: 10.16333/j.1001-6880.2015.10.023.

JING L L, MA H P, FAN P C, et al . In vitro free radical scavenging activity of ethanol extract of Cremanthodium humile and its protective effect on mice under hypobaric hypoxia condition[J ] . Nat Prod Res Dev, 2015, 27(10): 1815-1820. DOI: 10.16333/j.1001-6880.2015.10.023..

邵瑾, 马慧萍, 赵彤, 等. 矮垂头菊不同极性溶剂萃取物的抗氧化活性研究[J]. 化学研究与应用, 2019, 31(10): 1752-1759.

SHAO J, MA H P, ZHAO T, et al . Study on antioxidant activity of different polar solvent extracts of Cremanthodium humile [J ] . Chem Res Appl, 2019, 31(10): 1752-1759..

MA H P, FAN P C, JING L L, et al . Anti-hypoxic activity at simulated high altitude was isolated in petroleum ether extract of Saussurea involucrata [J ] . J Ethnopharmacol, 2011, 137(3): 1510-1515. DOI: 10.1016/j.jep.2011.08.037..

FAN P C, MA H P, JING L L, et al . The antioxidative effect of a novel free radical scavenger 4'-hydroxyl-2-substituted phenylnitronyl nitroxide in acute high-altitude hypoxia mice[J ] . Biol Pharm Bull, 2013, 36(6): 917-924. DOI: 10.1248/bpb.b12-00854.

BAIK A H. Hypoxia signaling and oxygen metabolism in cardio-oncology[J]. J Mol Cell Cardiol, 2022, 165: 64-75. DOI: 10.1016/j.yjmcc.2021.12.013.

APPLE F S, SANDOVAL Y, JAFFE A S, et al . Cardiac troponin assays: guide to understanding analytical characteristics and their impact on clinical care[J ] . Clin Chem, 2017, 63(1): 73-81. DOI: 10.1373/clinchem.2016.255109.

PU X Y, LI F X, LIN X, et al . Oxidative stress and expression of inflammatory factors in lung tissue of acute mountain sickness rats[J ] . Mol Med Rep, 2022, 25(2): 49. DOI: 10.3892/mmr.2021.12565.

GAO X, XU D R, ZHANG X Y, et al . Protective effect of lemon peel polyphenols on oxidative stress-induced damage to human keratinocyte HaCaT cells through activation of the Nrf2/HO-1 signaling pathway[J ] . Fron t Nutr, 2020, 7: 606776. DOI: 10.3389/fnut.2020.606776.

LAKSHMI SUNDARAM R, VASANTHI H R. Dalspinin isolated from Spermacoce hispida (Linn.) protects H9C2 cardiomyocytes from hypoxic injury by modulating oxidative stress and apoptosis[J ] . J Ethnopharmacol, 2019, 241: 111962. DOI: 10.1016/j.jep.2019.111962.

刘睿, 邵瑾, 赵彤, 等. 荠苧黄酮对低压低氧小鼠心肌组织损伤的改善作用与机制研究[J]. 中国新药杂志, 2021, 30(1): 55-61.

LIU R, SHAO J, ZHAO T, et al . Ameliorative effect and mechanism of mosloflavone on hypobaric hypoxia-induced heart damage in mice[J ] . Chin J New Drugs, 2021, 30(1): 55-61.

WANG X B, HOU Y, LI Q Y, et al . Rhodiola crenulata attenuates apoptosis and mitochondrial energy metabolism disorder in rats with hypobaric hypoxia-induced brain injury by regulating the HIF-1 α /microRNA 210/ISCU 1 /2(COX10) signaling pathway[J ] . J Ethnopharmacol, 2019, 241: 111801. DOI: 10.1016/j.jep.2019.03.028..

MURRAY A J. Energy metabolism and the high-altitude environment[J]. Exp Physiol, 2016, 101(1): 23-27. DOI: 10.1113/EP085317.

CHITRA L, BOOPATHY R. Altered mitochondrial biogenesis and its fusion gene expression is involved in the high-altitude adaptation of rat lung[J]. Respir Physiol Neurobiol, 2014, 192: 74-84. DOI: 10.1016/j.resp.2013.12.007.

孙杨, 魏崇莉, 赵彤, 等. 甘松乙酸乙酯部位改善低压和低氧诱导的心肌组织损伤作用及机制[J]. 中国现代中药, 2021, 23(1): 83-88. DOI: 10.13313/j.issn.1673-4890.20200312013.

SUN Y, WEI C L, ZHAOT, et al . Ethyl acetate extract fraction of Nardostachys chinensis ameliorates hypobaric hypoxia-induced myocardial injury via inhibiting oxidative stress[J ] . Mod Chin Med, 2021, 23(1): 83-88. DOI: 10.13313/j.issn.1673-4890.20200312013..

NITTI M, IVALDO C, TRAVERSO N, et al . Clinical significance of heme oxygenase 1 in tumor progression[J ] . Antioxidants (Basel), 2021, 10(5): 789. DOI: 10.3390/antiox10050789.

KIM S R, SEONG K J, KIM W J, et al . Epigallocatechin gallate protects against hypoxia-induced inflammation in microglia via NF-κB suppression and Nrf-2/HO-1 activation[J ] . Int J Mol Sci, 2022, 23(7): 4004. DOI: 10.3390/ijms23074004.

CHEN G, LIU G R, CAO D W, et al . Polydatin protects against acute myocardial infarction-induced cardiac damage by activation of Nrf2/HO-1 signaling[J ] . J Nat Med, 2019, 73(1): 85-92. DOI: 10.1007/s11418-018-1241-7.

HE P J, LI Y, ZHANG R T, et al . Role of p22phox and NOX5 in autophagy and apoptosis of osteoblasts induced by hypoxia[J ] . Chin J Repar Reconstr Surg, 2021, 35(7): 855-861. DOI: 10.7507/1002-1892.202008039.

ZHONG L H, JIA J, YE G H. Rian/miR-210-3p/Nfkb1 feedback loop promotes hypoxia-induced cell apoptosis in myocardial infarction through deactivating the PI3K/Akt signaling pathway[J]. J Cardiovasc Pharmacol, 2020, 76(2): 207-215. DOI: 10.1097/FJC.0000000000000824.

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