Protective Effect of Huangqi Baihe Granules on Acute Brain Injury in Rats with High Altitude Hypoxia Based on HIF-1<italic style="font-style: italic">α</italic>/NF-<italic style="font-style: italic">κ</italic>B/NLRP3 Signal Pathway

ZENG Yuanding; SU Yun; GONG Hongxia; CAO Wangjie; LIU Yongqi; HUANG Yong; LENG Guangxian; LI Lixia

doi:10.13422/j.cnki.syfjx.20222105

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Protective Effect of Huangqi Baihe Granules on Acute Brain Injury in Rats with High Altitude Hypoxia Based on HIF-1α/NF-κB/NLRP3 Signal Pathway

更新时间：2023-04-13

- Protective Effect of Huangqi Baihe Granules on Acute Brain Injury in Rats with High Altitude Hypoxia Based on HIF-1α/NF-κB/NLRP3 Signal Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 10, Pages: 134-141(2023)
- 作者机构：
  
  1.甘肃中医药大学基础医学院，兰州 730000
  2.甘肃省高校重大疾病分子医学与中医药防治研究省级重点实验室，兰州 730000
  3.兰州大学第二医院，兰州 730030
  4.天水市中西医结合医院，甘肃天水 741000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20222105
  CLC： R2-0;R22;R285.5;R289;R33
- Received：31 August 2022，
  
  Published Online：18 November 2022，
  
  Published：20 May 2023
- 稿件说明：
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曾元丁,苏韫,龚红霞等.基于HIF-1α/NF-κB/NLRP3信号通路探讨黄芪百合颗粒对高原低氧模型大鼠急性脑损伤的保护作用[J].中国实验方剂学杂志,2023,29(10):134-141.

ZENG Yuanding,SU Yun,GONG Hongxia,et al.Protective Effect of Huangqi Baihe Granules on Acute Brain Injury in Rats with High Altitude Hypoxia Based on HIF-1α/NF-κB/NLRP3 Signal Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(10):134-141.
曾元丁,苏韫,龚红霞等.基于HIF-1α/NF-κB/NLRP3信号通路探讨黄芪百合颗粒对高原低氧模型大鼠急性脑损伤的保护作用[J].中国实验方剂学杂志,2023,29(10):134-141. DOI： 10.13422/j.cnki.syfjx.20222105.

ZENG Yuanding,SU Yun,GONG Hongxia,et al.Protective Effect of Huangqi Baihe Granules on Acute Brain Injury in Rats with High Altitude Hypoxia Based on HIF-1α/NF-κB/NLRP3 Signal Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(10):134-141. DOI： 10.13422/j.cnki.syfjx.20222105.

摘要

目的

观察黄芪百合颗粒对高原低氧模型大鼠缺氧诱导因子-1

（HIF-1

）/核转录因子-

B（NF-

B）/NOD样受体热蛋白结构域相关蛋白3（NLRP3）信号通路的影响。

方法

60只SPF级SD雄性大鼠随机分为正常组、模型组、地塞米松组（5 mg·kg

-1

）、黄芪百合颗粒高、中、低剂量组（4.1、2.05、1.025 g·kg

-1

）。其中各中药组连续灌胃给药14 d，1次/d，连续3 d腹腔注射地塞米松作为阳性药物组；第15天将模型组、地塞米松组、黄芪百合颗粒高、中、低剂量组至动物低压模拟舱中模拟高海拔低压低氧环境进行暴露，持续暴露3 d，腹主动脉采血并分离血清，处死后摘取脑组织；苏木素-伊红（HE）染色法观察脑组织病理变化；酶联免疫吸附测定法（ELISA）检测大鼠血清中肿瘤坏死因子-

（TNF-

）、白细胞介素-6（IL-6）和白细胞介素-1

（IL-1

）的含量；蛋白免疫印迹法（Western blot）检测各组大鼠HIF-1

、NLRP3、磷酸化NF-

B（p-NF-

B）、NF-

B、消皮素D（GSDMD）和胱天蛋白酶-1（Caspase-1）蛋白的表达水平；实时荧光定量聚合酶链式反应（Real-time PCR）检测各组大鼠HIF-1

、NLRP3、NF-

B p65、GSDMD和Caspase-1 mRNA的表达水平。

结果

HE结果显示，与正常组比较，模型组大鼠脑组织病理切片可见锥体细胞排列松散且分布紊乱，大小不一；与模型组比较，地塞米松组及黄芪百合颗粒高、中剂量组锥体细胞病理改变减轻。ELISA结果显示，与正常组比较，模型组大鼠血清中TNF-

、IL-6和IL-1

的含量显著升高（

0.01）；与模型组比较，地塞米松组及黄芪百合颗粒高、中剂量组大鼠血清中TNF-

、IL-6和IL-1

的含量明显降低（

0.05，

0.01）。Western blot结果显示，与正常组比较，模型组大鼠脑组织中HIF-1

、NLRP3、p-NF-

B p65、GSDMD、Caspase-1蛋白相对表达水平均显著升高（

0.01）；与模型组比较，地塞米松组及黄芪百合颗粒高剂量组大鼠脑组织中HIF-1

、NLRP3、p-NF-

B p65、GSDMD、Caspase-1蛋白相对表达均明显降低（

0.05，

0.01），黄芪百合颗粒中剂量组大鼠脑组织中HIF-1

、NLRP3、p-NF-

B p65、Caspase-1蛋白相对表达均显著降低（

0.01），黄芪百合颗粒低剂量组大鼠脑组织中HIF-1

蛋白相对表达降低（

0.05）。Real-time PCR分析显示，与正常组比较，模型组大鼠脑组织HIF-1

、NLRP3、NF-

B p65、GSDMD和Caspase-1 mRNA表达水平显著增加（

0.01）；与模型组比较，地塞米松组大鼠脑组织中HIF-1

、NLRP3、NF-

B p65、GSDMD和Caspase-1 mRNA表达水平显著降低（

0.01）；黄芪百合颗粒高剂量组大鼠脑组织中HIF-1

、NF-

B p65、GSDMD和Caspase-1 mRNA表达水平显著降低（

0.01）；黄芪百合颗粒中剂量组大鼠脑组织中HIF-1

、NLRP3和Caspase-1 mRNA表达水平降低（

0.05，

0.01）。

结论

黄芪百合颗粒对低压低氧大鼠急性脑损伤的保护作用可能与HIF-1

/NF-

B/NLRP3信号通路相关。

Abstract

Objective

To observe the effect of Huangqi Baihe granules on the hypoxia-inducible factor 1

（HIF-1

）/nuclear factor-

B （NF-

B）/NOD-like receptor hot protein domain related protein 3 （NLRP3） signaling pathway in a rat model of high altitude hypoxia.

Method

Sixty male SPF SD rats were randomly divided into blank group， model group， dexamethasone group （5 mg·kg

-1

）， and high， middle， and low-dose groups of Huangqi Baihe granules （4.1， 2.05， 1.025 g·kg

-1

）. Among them， each Chinese medicine group was administrated orally for continuously 14 d， once a day， and the dexamethasone group was injected intraperitoneally for continuously 3 d as the positive control group. On the 15

d， the model group， dexamethasone group， and high， middle， and low dose groups of Huangqi Baihe granules were exposed to the simulated high altitude， low pressure， and low oxygen environment in the animal low-pressure simulation cabin， and the exposure lasted for 3 d. Blood was collected from the abdominal aorta and serum was separated， and the brain tissue was taken after being killed. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in brain tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect the content of tumor necrosis factor-

（TNF-

）， interleukin-6 （IL-6）， and interleukin-1

（IL-1

） in rat serum. Western blot was used to detect HIF-1

， NLRP3， phosphorylated nuclear factor-

B （p-NF-

B）， NF-

B， desquamation D （GSDMD）， and cysteine aspartate-specitis protein-1（Caspase-1） in rats of each group. The mRNA expression levels of HIF-1

， NLRP3， NF-

B p65， GSDMD， and Caspase-1 were detected by real-time quantitative polymerase chain reaction （Real-time PCR）.

Result

The results of HE staining showed that as compared with the normal group， the pathological sections of brain tissues in the model group showed that pyramidal cells were loosely arranged and distributed in disorder， with different sizes. Compared with the model group， the pathological changes in pyramidal cells in the dexamethasone group and high and middle-dose groups of Huangqi Baihe granules were reduced. The results of ELISA showed that as compared with the normal group， the content of TNF-

， IL-6， and IL-1

in the serum of rats in the model group was significantly higher （

0.01）. Compared with the model group， the content of TNF-

， IL-6， and IL-1

in the serum of rats in the dexamethasone group and high and middle-dose groups of Huangqi Baihe granules decreased significantly （

0.05，

0.01）. The results of Western blot showed that as compared with the normal group， the relative protein expression levels of HIF-1

， NLRP3， p-NF-

B p65， GSDMD， and Caspase-1 in the brain tissue of the model group were significantly higher （

0.01）. As compared with the model group， the relative expressions of HIF-1

， NLRP3， p-NF-

B p65， GSDMD， and Caspase-1 in the brain tissue of rats in the dexamethasone group and the high-dose group of Huangqi Baihe granules were significantly decreased （

0.05，

0.01）. The relative protein expression levels of HIF-1

， NLRP3， p-NF-

B p65， and Caspase-1 in the brain tissue of rats in the middle-dose group of Huangqi Baihe granules decreased significantly （

0.01）， and the relative protein expression of HIF-1

in the brain tissue of rats in the low-dose group of Huangqi Baihe granules was reduced （

0.05）. The Real-time PCR analysis showed that as compared with the normal group， the mRNA expression levels of HIF-1

， NLRP3， NF-

B p65， GSDMD， and Caspase-1 in the brain tissue of the model group were significantly increased （

0.01）. As compared with the model group， the mRNA expression levels of HIF-1

， NLRP3， NF-

B p65， GSDMD， and Caspase-1 in the brain tissue of rats in the dexamethasone group were significantly decreased （

0.01）. The mRNA expression levels of HIF-1

， NF-

B p65， GSDMD， and Caspase-1 in the brain tissue of rats in the high-dose group of Huangqi Baihe granules decreased significantly （

0.01）. The mRNA expression levels of HIF-1

， NLRP3， and Caspase-1in the brain tissue of rats in the middle-dose group of Huangqi granules decreased （

0.05，

0.01）.

Conclusion

The protective effect of Huangqi Baihe granules on acute brain injury in low-pressure hypoxic rats may be related to the HIF-1

/NF-

B/NLRP3 signaling pathway.

关键词

Keywords

references

刘凤英，马海英 . 高原环境脑损伤与药物治疗研究进展［J］. 国际药学研究杂志， 2019 ， 46 （ 6 ）： 418 - 422 .

靳国恩，格日力 . 高原低氧与脑组织结构和功能损伤［J］. 中国高原医学与生物学杂志， 2021 ， 42 （ 3 ）： 185 - 189 .

XU L U ， SONG H U A ， QIU Q I ， et al . Different expressions of HIF-1 α and metabolism in brain and major visceral organs of acute hypoxic mice ［J］. Int J Mol Sci ， 2021 ， 22 （ 13 ）： 6705 .

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 .

张晋玮，贾延劼 . 创伤性脑损伤后炎性小体介导细胞焦亡作用机制及靶向治疗药物研究进展［J］. 中华创伤杂志， 2021 ， 37 （ 3 ）： 278 - 283 .

YU E ， ZHANG E ， LV X ， et al . LDC7559 exerts neuroprotective effects by inhibiting GSDMD-dependent pyroptosis of microglia in mice with traumatic brain injury ［J］. J Neurotrauma ， 2022 ， doi： 10.1089/neu.2021.0318 http://dx.doi.org/10.1089/neu.2021.0318 .

成新平，苏韫，颜春鲁，等 . 黄芪百合颗粒对常压缺氧小鼠脑组织的保护作用［J］. 解放军药学学报， 2017 ， 33 （ 5 ）： 425 - 427 .

卢志伟，安方玉，骆亚莉，等 . 黄芪百合颗粒对高原低氧模型小鼠脑氧化应激损伤的影响［J］. 解放军药学学报， 2016 ， 32 （ 4 ）： 302 - 306 .

任春贞，骆亚莉，刘永琦，等 . 黄芪百合颗粒对高原低氧模型小鼠肺自由基代谢及肺病理形态学改变的影响［J］. 重庆医科大学学报， 2017 ， 42 （ 9 ）： 1126 - 1130 .

李玲，安方玉，刘永琦，等 . 黄芪百合颗粒对高原低氧模型小鼠肠黏膜屏障的保护作用［J］. 解放军医学杂志， 2016 ， 41 （ 9 ）： 773 - 778 .

王继龙，魏舒畅，刘永琦，等 . 黄芪百合颗粒干法制粒工艺研究［J］. 中药材， 2017 ， 40 （ 3 ）： 670 - 672 .

徐叔云，卞如濂，陈修 . 药理实验方法学［M］. 3版 . 北京：人民卫生出版社， 2002 .

王新芳，张宇忠，任丽薇，等 . 地塞米松对内毒素休克大鼠脑组织细胞因子含量的影响［J］. 中国康复理论与实践， 2011 ， 17 （ 9 ）： 834 - 836 .

夏金婵，从人愿，袁静，等 . 黄芩苷通过p38 MAPK/NLRP3通路对脂多糖诱导大鼠急性肺损伤的影响［J］. 中国实验方剂学杂志， 2022 ， 28 （ 2 ）： 79 - 86 .

陈嘉怡，尤伟杰，王伟，等 . 模拟高原低氧脑组织损伤动物模型的制备与评价［J］. 军事医学， 2019 ， 43 （ 10 ）： 778 - 782，796 .

周子懿，王立新，黄培新 . 脑水肿的中医证治探讨［J］. 中华中医药杂志， 2020 ， 35 （ 2 ）： 760 - 763 .

任春贞，刘永琦，骆亚莉，等 . 从中医学角度探讨高原低氧对机体损伤机理［J］. 甘肃科技， 2016 ， 32 （ 4 ）： 121 - 123 .

AMIN N ， CHEN S ， REN Q ， et al . Hypoxia inducible factor-1 α attenuates ischemic brain damage by modulating inflammatory response and glial activity ［J］. Cells ， 2021 ， 10 （ 6 ）： 1359 .

ZHOU Y Z ， HUANG X ， ZHAO T ， et al . Hypoxia augments LPS-in-duceinflammation and triggers high altitude cerebtal edema in mice ［J］. Brain Behav Immun ， 2017 ， 64 （ 8 ）： 266 - 275 .

DAVIS C ， HACKEETT P . Advances in the prevention and treatment of high-altitude illness ［J］. Emerg Med Clin North Am ， 2017 ， 35 ： 241 - 260 .

HAO G S ， FAN Q L ， HU Q Z ， et al . Research progress on the mechanism of cerebral blood flow regulation in hypoxia environment at plateau ［J］. Bioengineered ， 2022 ， 13 （ 3 ）： 6353 - 6358 .

SAJJA R K ， RAHMAN S ， CUCULLO L . Drugs of abuse and blood-brain barrier endothelial d ysfunction： A focus on the role of oxidative stress ［J］. J Cereb Blood Flow Metab ， 2016 ， 36 ： 539 - 554 .

GONG G ， YIN L ， YUAN L ， 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 .

CIMMINO F ， AVITABILE M ， LASORSA V A ， et al . HIF-1 transcription activity： HIF1A driven response in normoxia and in hypoxia ［J］. BMC Med Genet ， 2019 ， 20 （ 1 ）： 37 .

PENG X W ， LI C L ， YU W L ， et al . Propofol attenuates hypoxia-induced inflammation in BV2 microglia by inhibiting oxidative stress and NF- κ B/Hif-1 signaling ［J］. Biomed Res Int ， 2020 ： 8978704 .

ABDEL-RAHMAN MOHAMED A ， M M METWALLY M ， KHALIL S R ， et al . Moringa oleifera extract attenuates the CoCl 2 induced hypoxia of rat's brain： Expression pattern of HIF-1 α ，NF- κ B，MAO and EPO ［J］. Biomed Pharmacother ， 2019 ， 109 ： 1688 - 1697 .

TAYLOR C T . Interdependent roles for hypoxia inducible factor and nuclear factor- κ B in hypoxic inflammation ［J］. J Physiol ， 2008 ， 586 （ 17 ）： 4055 - 4059 .

TANG X ， GUO D ， LIN C ， et al . hCLOCK induction by hypoxia promotes inflammatory responses by activating the NF- κ B pathway ［J］. Mol Med Rep ， 2017 ， 15 （ 3 ）： 1401 - 1406 .

ESPINOSA-GARCIA C ， ATIF F ， YOUSUF S ， et al . Progesterone attenuates stress-induced NLRP3 inflammasome activation and enhances autophagy following ischemic brain injury ［J］. Int J Mol Sci ， 2020 ， 26；21 （ 11 ）： 3740 .

孙健，沈巨信 . 炎症及细胞自噬与急性肺损伤关系的研究进展［J］. 中国免疫学杂志， 2019 ， 35 （ 17 ）： 2163 - 2168 .

GU L G ， SUN M J ， LI R H ， et al . Didymin suppresses microglia pyroptosis and neuroinflammation through the Asc/Caspase-1/GSDMD pathway following experimental intracerebral hemorrhage ［J］. Front Immunol ， 2022 ， 13 ： 810582 .

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Protective Effect of Huangqi Baihe Granules on Acute Brain Injury in Rats with High Altitude Hypoxia Based on HIF-1α/NF-κB/NLRP3 Signal Pathway

DOI：10.13422/j.cnki.syfjx.20222105

摘要

Abstract

关键词

Keywords

references