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中国临床药理学与治疗学 ›› 2025, Vol. 30 ›› Issue (10): 1391-1399.doi: 10.12092/j.issn.1009-2501.2025.10.011

• 药物治疗学 • 上一篇    下一篇

安宫牛黄丸联合常规治疗对痰热内闭型脑出血患者神经功能恢复的影响:基于AMPK-PGC1α-NRF2通路的随机对照研究

武雨幸1,2,李  祎1,2,岳晓晴2,张晨露2,张燕平1   

  1. 1河南中医药大学第一附属医院脑病中心,郑州  450000,河南;2河南中医药大学第一临床医学院,郑州  450000,河南

  • 收稿日期:2025-02-25 修回日期:2025-04-01 出版日期:2025-10-26 发布日期:2025-10-15
  • 通讯作者: 张燕平,女,硕士,主任医师,硕士生导师,研究方向:脑血管疾病。 E-mail: zhypkaya@126.com
  • 作者简介:武雨幸,女,硕士研究生在读,研究方向:脑血管疾病。 E-mail: 18235276177@163.com
  • 基金资助:
    河南省中医药科学研究专项课题(2024ZY1007);河南省中医药科学研究专项(2022ZY1009)

Effect of Angong Niuhuang pill combined with conventional treatment on neurological function recovery in patients with phlegm-heat internal closed cerebral hemorrhage: A randomized controlled trial based on the AMPK-PGC1α-NRF2 pathway

WU Yuxing1,2, Li Yi1,2, YUE Xiaoqing2, ZHANG Chenlu2, ZHANG Yanping1   

  1. 1Brain Disease Center, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan, China; 2The First Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou 450000, Henan, China
  • Received:2025-02-25 Revised:2025-04-01 Online:2025-10-26 Published:2025-10-15

摘要:

目的:探讨安宫牛黄丸联合常规治疗对痰热内闭型脑出血(ICH)患者神经功能恢复的影响,评估安宫牛黄丸在改善患者神经功能、促进脑组织修复及抗氧化应激等方面的疗效,并基于AMPK-PGC1α-NRF2通路,揭示其潜在的作用机制。方法:选取痰热内闭型ICH患者130例,采用随机数字表法分为对照组(常规治疗)和研究组(安宫牛黄丸联合常规治疗),每组65例。收集治疗后两组患者美国国立卫生研究院卒中量表(NIHSS)评分、格拉斯哥昏迷量表(GCS)评分、改良Rankin量表(mRS)评分及机体组织中腺苷酸活化蛋白激酶(AMPK)、过氧化物酶体增殖物激活受体γ共激活因子1α(PGC1α)、核因子E2相关因子2(NRF2)表达水平,血清超氧化物歧化酶(SOD)、丙二醛(MDA)、活性氧(ROS)、白介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、谷胱甘肽过氧化物酶4(GPX4)、酰基辅酶A合成酶长链家族成员4(ACSL4)、铁离子水平、血肿体积、脑水肿体积和不良反应发生率,评估整体疗效。结果:对照组和研究组各入组65例。治疗后,研究组NIHSS评分[(9.97±1.22)分]和mRS评分[(2.29±0.33)分]均低于对照组[(11.17±1.52)分和(2.64±0.45)分](P<0.05);研究组 GCS评分[(14.57±1.19)分]高于对照组[(13.18±1.05)分](P<0.05)。治疗后,研究组患者AMPK[(3.34±0.81) ng/mL]、PGC1α[(2.30±0.67) ng/mL]、NRF2[(3.72±0.85) ng/mL]在组织中的表达高于对照组[(2.63±0.65) ng/mL、(1.83±0.70) ng/mL、(2.91±0.96) ng/mL](P<0.05)。治疗后,研究组患者血清SOD[(98.76±6.67) U/mL]、IL-10[(40.37±5.61) pg/mL]水平高于对照组[(89.65±6.89) U/mL、(35.69±4.65) pg/mL](P<0.05);研究组患者血清MDA[(3.36±0.62) nmol/mL]、ROS[(126.35±23.74) U/mL]、TNF-α[(17.22±2.07) pg/mL]、IL-6[(33.37±3.76) pg/mL]水平低于对照组[(3.76±0.83) nmol/mL、(159.85±26.67) nmol/mL、(19.15±2.34) nmol/mL、(41.26±4.91)  nmol/mL](P<0.05)。治疗后,研究组患者血清GPX4水平[(9.87±1.25) ng/mL]高于对照组[(8.16±1.12) ng/mL](P<0.05);研究组患者血清ACSL4[(8.74±1.45) ng/mL]、铁离子水平[(27.44±3.35) μmol/L]低于对照组[(10.12±2.11) ng/mL、(30.46±3.17) μmol/L](P<0.05)。治疗后,研究组血肿体积[(6.46±1.13) mL]和脑水肿体积[(11.47±1.76) mL]较对照组[(8.71±1.02) mL、(3.41±2.04) mL]改善更佳(P<0.05)。结论:安宫牛黄丸联合常规治疗在改善患者神经功能、促进脑组织修复及抗氧化应激等方面具有显著疗效,应用价值高。

关键词: 安宫牛黄丸, 痰热内闭型脑出血, 神经功能恢复, 抗氧化应激, 炎症因子, 铁死亡相关标志物, 影像学

Abstract:

AIM: To examine the impact of Angong Niuhuang pill in conjunction with conventional therapy on the recovery of neurological function in patients with cerebral hemorrhage (ICH) characterized by phlegm-heat internal obstruction, and to evaluate its efficacy in enhancing neurological function, promoting brain tissue repair, and mitigating oxidative stress. Additionally, this study aims to elucidate the potential mechanisms underlying these effects through the AMPK-PGC1α-Nrf2 pathway. METHODS: A total of 130 patients with ICH characterized by phlegm-heat internal closure were recruited and randomly allocated into a control group (receiving conventional treatment) and a study group (receiving Angong Niuhuang pill in combination with conventional treatment) using the random number table method, with 65 cases in each group. Post-treatment assessments included the National Institutes of Health Stroke Scale (NIHSS) score, Glasgow Coma Scale (GCS) score, modified Rankin scale (mRS) score, as well as tissue levels of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1α), and nuclear factor erythroid 2-related factor 2 (NRF2). Additionally, serum levels of superoxide dismutase (SOD), malondialdehyde (MDA), reactive oxygen species (ROS), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), glutathione peroxidase 4 (GPX4), acyl-coenzyme A synthetase long-chain family member 4 (ACSL4), iron ions, tumor volume, brain edema volume, and the incidence of adverse reactions were evaluated. RESULTS: Each group comprised 65 cases. Post-treatment, the NIHSS score (9.97±1.22) and mRS score (2.29±0.33) in the Research Group were significantly lower than those in the Control Group (11.17±1.52 and 2.64±0.45, respectively), with p-values less than 0.05. Additionally, the GCS score for the Research Group (14.57±1.19) was notably higher compared to the control group (13.18±1.05) (P<0.05). After treatment, the expressions of AMPK [(3.34±0.81) ng/mL], PGC1α [(2.30±0.67) ng/mL] and NRF2 [(3.72±0.85) ng/mL] in the tissues of the group were higher than those of the control group [(2.63±0.65) ng/mL, (1.83±0.70) ng/mL, (2.91±0.96) ng/mL] (P<0.05). After treatment, the levels of serum SOD [(98.76±6.67) U/mL] and IL-10 [(40.37±5.61) pg/mL] in the research group were higher than those in the Control group group [(89.65±6.89) U/mL, (35.69±4.65) pg/mL] (P<0.05); the serum levels of MDA [(3.36±0.62) nmol/mL], ROS [(126.35±23.74) U/mL], TNF-α [(17.22±2.07) pg/mL] and IL-6 [(33.37±3.76) pg/mL] in the group were lower than those in the control group group [(3.76±0.83) nmol/mL, (159.85±26.67) nmol/mL, (19.15±2.34) nmol/mL, (41.26±4.91) nmol/mL] (P<0.05). After treatment, the serum GPX4 level in the Research Group [(9.87±1.25) ng/mL] was higher than that in the control group [(8.16±1.12) ng/mL] (P<0.05). The serum levels of ACSL4 [(8.74±1.45) ng/mL] and iron ion [(27.44±3.35) μmol/L] in the study group were lower than those in the control group (10.12±2.11) ng/mL, (30.46±3.17) μmol/L] (P<0.05). After treatment, the hematoma volume [(6.46±1.13) mL] and brain edema volume [(11.47±1.76) mL] in the research group were better than those in the Control group [(8.71±1.02) mL, (3.41±2.04) mL] (P<0.05). CONCLUSION: The combination of Angong Niuhuang pill with conventional treatment demonstrates significant efficacy in improving neurological function, promoting brain tissue repair, and alleviating oxidative stress, thereby exhibiting high application value in clinical practice.

Key words: Angong Niuhuang pill, phlegm-heat internal closed intracerebral hemorrhage, recovery of neurological function, anti-oxidative stress, inflammatory factors, ferroptosis-related markers, imaging

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