Protective effect of Danqijing granules on acute high altitude exposure: A field cohort study on plateau
-
摘要:
背景 急进高原作训如果减少阶梯习服或低氧预适应训练，会增加急性高原病(AMS)的发生风险。AMS是因急性缺氧而引起的潜在致命性疾病，可直接导致作训减员。因此，积极进行药物研发，预防AMS的发生具有十分重要的意义。 目的 观察口服丹芪精颗粒对快速进入高原地区人员发生急性高原反应的防护作用。 方法 以2022年6月某部参加高原训练分队的男性官兵为研究对象，采用前瞻性、随机、对照临床试验设计，共纳入80例(18 ~ 35岁官兵)，随机分为治疗组和对照组，每组40例。治疗组口服丹芪精颗粒(主要由黄芪、丹参、黄精等药物组成)，对照组口服红景天胶囊(主要成分为红景天)，于进驻高原前7天开始口服，共给予14天。比较两组在进驻高原后第1天(T1)、第3天(T2)、第7天(T3)时一般情况、中医证候分级量化表和AMS量表评分、血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)水平及药物安全性指标。 结果 两组受试者的收缩压(mm/Hg)，舒张压(mm/Hg)，心率(次/分)，SpO2(%)在各个时间点比较无统计学意义(P＞0.05)。两组进驻高原后第7天中医证候积分与本组进驻高原后第1天比较均下降显著(P<0.05)，且治疗组较对照组下降显著(P<0.01)。与进驻第1天比较，在进驻第3天、7天时两组TNF-α、IL-6水平均降低(P<0.01)，且治疗组优于对照组(P<0.05)。IL-8水平及AMS发生率组间差异无统计学意义(P＞0.05)。肝、肾等指标均未见异常。 结论 丹芪精颗粒可减少中医证候分级量化表评分，改善急进高原人员临床症状；可能通过降低血清TNF-α、IL-6水平，对急性高原暴露人员发生AMS起到防护作用。 Abstract:Background The risk of acute mountain sickness (AMS) will increase if steps or hypoxic preconditioning training is reduced. AMS is a potentially fatal disease caused by acute hypoxia that can directly lead to training force reductions. Therefore, it is of great significance to actively conduct drug research and development to prevent AMS. Objective To observe the protective effect of oral Danqijing granules on acute altitude sickness in people who quickly enter plateau area. Methods A prospective, randomized, controlled clinical trial design was conducted to select 80 male officers and soldiers (18-35 years old) who participated in altitude training in June 2022, and they were randomly divided into treatment group and control group with 40 cases in each group. The treatment group was given Danqijing granules (mainly composed of Radix Astragalus, Salvia miltiorrhiza, Huangjing), while the control group was given Rhodiola Rosea capsules (mainly composed of Rhodiola Rosea), starting from 7 days before entering the plateau, for a total of 14 days. The general conditions of the two groups on day 1 (T1), day 3 (T2) and day 7 (T3) after admission to plateau were compared, including the TCM syndrome grading scale, AMS scale score, serum Tumor Necrosis Factor-α(TNF-α), Interleukin-6 (IL-6), Interleukin-8 (IL-8) levels and drug safety indexes. Results There were no significant differences in systolic blood pressure (mm/Hg), diastolic blood pressure (mm/Hg), heart rate (times/min), SpO 2 (%) between the two groups at each time point (all P>0.05). The scores of TCM symptoms on day 7 after the two groups decreased significantly compared with that on day 1 after the two groups were stationed at the plateau (P<0.05). Compared with the control group, the scores of TCM symptoms in the treatment group decreased significantly (P<0.01) on the first and seventh days after entering the plateau. Compared with day 1, the levels of TNF-αand IL-6 in both groups were decreased on day 3 and day 7 (P<0.01), and the treatment group was better than the control group (P<0.05). There were no significant differences in IL-8 level and AMS incidence among groups (P> 0.05). Liver, kidney and other indicators were all normal. Conclusion Danqijing granules can reduce the score of TCM syndrome grading scale and improve the clinical symptoms of patients who rush to plateau. It may reduce the serum levels of TNF-α and IL-6 to protect against AMS in people with acute altitude exposure. -
Key words:
- Danqijing granule /
- acute plateau exposure /
- TCM syndrome /
- TNF-α /
- IL-6
-
表 1 两组基线资料比较
Table 1. Comparison of baseline data between the two groups
指标 治疗组(n=40) 对照组(n=40) t值 P值 年 龄/岁 24.20 ± 3.33 25.60 ± 3.91 1.725 0.089 身 高/cm 173.48 ± 5.12 173.40 ± 5.77 0.062 0.951 体 重/kg 66.32 ± 8.45 69.46 ± 8.37 1.669 0.099 心 率/(次/分) 75.13 ± 8.82 73.18 ± 11.18 0.866 0.389 收缩压/(mmHg) 117.88 ± 8.13 116.00 ± 8.96 0.980 0.330 舒张压/(mmHg) 71.70 ± 9.27 68.58 ± 7.27 1.677 0.097 SpO2/% 96.23 ± 4.33 96.50 ± 2.05 0.363 0.718 
下载: 导出CSV
表 2 两组干预后基础指标比较
Table 2. Comparison of general conditions before and after treatment between the two groups
指标 时间点 治疗组(n=40) 对照组(n=40) 球形检验(Huynh-Feldt ε) 组间(F,P) 时间(F,P) 交互(F,P) 收缩压/(mmHg) T1 127.42 ± 10.70 123.98 ± 11.61 0.982 0.847,0.363 1.261,0.295 0.447,0.643 T2 126.05 ± 8.21 123.63 ± 10.38 T3 125.78 ± 8.90 124.28 ± 7.11 舒张压/(mmHg) T1 81.25 ± 9.19 79.00 ± 8.94 0.935 1.536,0.223 2.681,0.081 0.134,0.875 T2 78.65 ± 8.44 77.28 ± 8.91 T3 80.30 ± 9.28 78.18 ± 7.97 心率/(次/分) T1 82.85 ± 12.45 82.53 ± 10.16 0.976 0.071,0.931 0.038,0.846 1.116,0.338 T2 82.08 ± 9.40 84.33 ± 11.07 T3 83.53 ± 10.42 82.73 ± 8.87 SpO2/% T1 85.45 ± 5.44 86.53 ± 4.90 1.000 0.436,0.513 0.429,0.654 1.573,0.221 T2 86.55 ± 4.86 84.93 ± 7.28 T3 86.82 ± 4.34 85.93 ± 4.00
下载: 导出CSV
表 3 进驻高原后两组AMS发生率比较[例(%)]
Table 3. Comparison of AMS severity in two groups at different time points after rushing to plateau (n [%])
指标 时间点 治疗组(n=40) 对照组(n=40) χ2值 P值 T1 无症状 39(97.50) 35(87.50) 8.000 0.238 轻度 1(2.50) 2(5.00) 中度 0(0) 0(0) 重度 0(0) 3(7.50) T2 无症状 37(92.50) 36(90.00) 12.000 0.213 轻度 2(5.00) 1(2.50) 中度 1(2.50) 3(7.50) 重度 0(0) 0(0) T3 无症状 40(100.00) 37(92.50) 4.000 0.135 轻度 0(0) 3(7.50) 中度 0(0) 0(0) 重度 0(0) 0(0)
下载: 导出CSV
表 4 两组干预后中医证候分级量化表评分比较[Md(IQR), 分]
Table 4. Comparison of TCM syndrome grading scale scores before and after treatment between the two groups (Md[IQR],score)
组 别 中医证候分级量化表评分 t P 治疗组(n=40) 对照组(n=40) T1 1.80 ± 1.99 1.70 ± 2.11 0.218 0.828 T7 0.38 ± 0.63 0.88 ± 1.38 2.085
0.0400
t 4.320 2.066 P ＜0.001 0.042
下载: 导出CSV
表 5 两组干预后血清炎症因子相关指标比较(pg/mL)
Table 5. Comparison of serum inflammatory cytokines before and after treatment between the two groups (pg/mL)
指标 时间点 治疗组(n=40) 对照组(n=40) 球形检验(Huynh-Feldt ε) 组间(F, P) 时间(F, P) 交互(F, P) IL-6 T1 32.25 ± 11.93 33.60 ± 16.68 0.995 732.53,
＜0.001143.93,
＜0.0014.990,
0.009T2 38.58 ± 10.91 37.72 ± 11.41 T3 14.77 ± 7.39 21.45 ± 12.40a IL-8 T1 414.03 ± 164.00 418.22 ± 358.05 0.830 1.085,
0.30113.217,
＜0.0012.487,
0.086T2 502.93 ± 218.18 668.75 ± 882.85 T3 349.21 ± 210.41 481.14 ± 572.68a TNF-a T1 37.03 ± 11.83 44.85 ± 23.06 0.973 5.064,
0.02697.039,
＜0.0013.339,
0.041T2 43.97 ± 13.27 48.78 ± 26.06 T3 19.93 ± 8.96 32.53 ± 22.40 aP<0.05, vs 治疗组
下载: 导出CSV
-
[1] Roach RC,Hackett PH,Oelz O,et al. The 2018 lake louise acute mountain sickness score[J]. High Alt Med Biol,2018,19(1): 4-6. doi: 10.1089/ham.2017.0164 [2] Ke JB, Liu C, Yu SY, et al. Low stroke volume index in healthy young men is associated with the incidence of acute mountain sickness after an ascent by airplane: a case-control study[J/OL].https: //doi.org/10.1155/2020/6028747. [3] Kammerer T,Faihs V,Hulde N,et al. Hypoxic-inflammatory responses under acute hypoxia:in Vitro experiments and prospective observational expedition trial[J]. Int J Mol Sci,2020,21(3): 1034. [4] Cao CZ,Zhang H,Huang YC,et al. The combined use of acetazolamide and Rhodiola in the prevention and treatment of altitude sickness[J]. Ann Transl Med,2022,10(10): 541. doi: 10.21037/atm-22-2111 [5] El Alam S,Pena E,Aguilera D,et al. Inflammation in pulmonary hypertension and edema induced by hypobaric hypoxia exposure[J]. Int J Mol Sci,2022,23(20): 12656. doi: 10.3390/ijms232012656 [6] Wang C,Jiang H,Duan JY,et al. Exploration of acute phase proteins and inflammatory cytokines in early stage diagnosis of acute mountain sickness[J]. High Alt Med Biol,2018,19(2): 170-177. doi: 10.1089/ham.2017.0126 [7] Qin L, Tan HL, Wang YG, et al. Astragalus membranaceus and Salvia miltiorrhiza ameliorate lipopolysaccharide-induced acute lung injury in rats by regulating the toll-like receptor 4/nuclear factor-kappa B signaling pathway[J/OL].https://doi.org/10.1155/2018/3017571. [8] 秦丽,窦永起,李敏,等. 益气活血中药预处理对脂多糖致大鼠急性肺损伤早期炎性因子的影响[J]. 中华中医药杂志,2017,32(2): 717-720. [9] Qin L,Li M,Tan HL,et al. Mechanistic target of rapamycin-mediated autophagy is involved in the alleviation of lipopolysaccharide-induced acute lung injury in rats[J]. Int Immunopharmacol,2020,78: 105790. doi: 10.1016/j.intimp.2019.105790 [10] 尹昭云,谢印芝,牛文忠,等. 急性高原反应的诊断和处理原则[J]. 解放军预防医学杂志,1997,15(6): 395-397. doi: 10.13704/j.cnki.jyyx.1997.06.002 [11] 郑筱萸. 中药新药临床研究指导原则: 试行[M]. 北京: 中国医药科技出版社, 2002: 28-31. [12] 蒲玲玲,李天,王永辉,等. 部队急进高原损伤防治措施研究进展[J]. 解放军预防医学杂志,2018,36(12): 1619-1621. doi: 10.13704/j.cnki.jyyx.2018.12.042 [13] 温若卿,李雪燕,陈开兵,等. 高原武警官兵中医体质现状及相关性分析[J]. 世界睡眠医学杂志,2021,8(7): 1122-1124. doi: 10.3969/j.issn.2095-7130.2021.07.002 [14] 杜辉,张锦花,王处渊,等. 防治高原反应中药述评[J]. 世界睡眠医学杂志,2020,7(3): 436-440. doi: 10.3969/j.issn.2095-7130.2020.03.028 [15] Jia SN,Zhang QG,Chun-Hua MA,et al. Proteomics analysis of erythrocyte membrane in rats with high altitude polycythemia before and after intervention with salidroside[J]. China J Chin Mater Med,2020,45(19): 4719-4724. [16] MEIm XD,Cao YF,Che YY,et al. Danshen:a phytochemical and pharmacological overview[J]. Chin J Nat Med,2019,17(1): 59-80. [17] 王焱,王雅西,严晓燕,等. 复方丹参滴丸联合氧疗对急进高原习服的作用[J]. 中华保健医学杂志,2017,19(4): 345 doi: 10.3969/.issn.1674-3245.2017.04.021 [18] Su HF,Shaker S,Kuang Y,et al. Phytochemistry and cardiovascular protective effects of Huang-Qi (Astragali Radix)[J]. Med Res Rev,2021,41(4): 1999-2038. doi: 10.1002/med.21785 [19] Guo ZZ,Lou YM,Kong MY,et al. A systematic review of phytochemistry,pharmacology and pharmacokinetics on Astragali Radix:implications for Astragali radix as a personalized medicine[J]. Int J Mol Sci,2019,20(6): 1463. doi: 10.3390/ijms20061463 [20] 陶文迪,田秀玉,李茂星,等. 黄芪水提取物对高原缺氧大鼠运动能力的影响[J]. 解放军医药杂志,2019,31(12): 12-18. doi: 10.3969/j.issn.2095-140X.2019.12.003 [21] Liu XR,Zhang H,Yan JX,et al. Deciphering the efficacy and mechanism of Astragalus membranaceus on high altitude polycythemia by integrating network pharmacology and in vivo experiments[J]. Nutrients,2022,14(23): 4968. doi: 10.3390/nu14234968 [22] 雷升萍,龙子江,施慧,等. 黄精多糖对缺氧复氧诱导H9c2心肌细胞损伤的保护作用[J]. 中药药理与临床,2017,33(1): 102-106. doi: 10.13412/j.cnki.zyyl.2017.01.028 [23] Pu XY,Li FX,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. [24] Lim JU,Choi JY,Jeong HJ,et al. Comparison of clinical characteristics and inflammatory cytokines between hypoxemic and non-hypoxemic human adenovirus 55 pneumonia[J]. J Thorac Dis,2020,12(8): 4044-4056. doi: 10.21037/jtd-19-4067 [25] del Valle DM,Kim-Schulze S,Huang HH,et al. An inflammatory cytokine signature predicts COVID-19 severity and survival[J]. Nat Med,2020,26(10): 1636-1643. doi: 10.1038/s41591-020-1051-9 -
下载: 
点击查看大图
表(5)
计量
- 文章访问数: 47
- HTML全文浏览量: 12
- PDF下载量: 4
- 被引次数: 0
