[1]丁国瑞,贾壮壮,赵铎.三七总皂苷通过调控ERK/mTOR信号通路对肺动脉高压大鼠氧化应激水平的影响[J].陕西中医,2025,46(10):1312-1317.[doi:DOI:10.3969/j.issn.1000-7369.2025.10.003]
　DING Guorui,JIA Zhuangzhuang,ZHAO Duo.Effects of panax notoginseng total saponins on oxidative stress levels in pulmonary hypertension rats by regulating the ERK/mTOR signaling pathway[J].,2025,46(10):1312-1317.[doi:DOI:10.3969/j.issn.1000-7369.2025.10.003]
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三七总皂苷通过调控ERK/mTOR信号通路对肺动脉高压大鼠氧化应激水平的影响

《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
46
期数:
2025年10期
页码:
1312-1317
栏目:
基础研究
出版日期:
2025-10-05

文章信息/Info

Title:
Effects of panax notoginseng total saponins on oxidative stress levels in pulmonary hypertension rats by regulating the ERK/mTOR signaling pathway
作者:
丁国瑞1; 2; 贾壮壮3; 赵铎2
（1.天津中医药大学，天津 301617；2.天津中医药大学第一附属医院 国家中医针灸临床医学研究中心，天津 300381；3.云南中医药大学，云南 昆明 650500）
Author(s):
DING Guorui1; 2; JIA Zhuangzhuang3; ZHAO Duo2
（1.Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China；2.First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,Tianjin 300381,China；3.Yunnan University of Chinese Medicine,Kunming 650500,China）
关键词:
肺动脉高压; 氧化应激; ERK/mTOR信号通路; 三七总皂苷; 血管重塑
Keywords:
Pulmonary hypertension; Oxidative stress; ERK/mTOR signaling pathway; Panax notoginseng total saponins; Vascular remodeling
分类号:
R 256.2
DOI:
DOI:10.3969/j.issn.1000-7369.2025.10.003
文献标志码:
A
摘要:
目的：探讨三七总皂苷通过调控ERK/mTOR信号通路对肺动脉高压（PH）大鼠氧化应激水平的影响。方法：采用野百合碱（MCT）诱导PH大鼠模型，将48只雄性SPF级SD大鼠随机分为对照组、模型组、西地那非组、三七总皂苷低剂量组、三七总皂苷中剂量组及三七总皂苷高剂量组，每组各8只。三七总皂苷低、中、高剂量组分别按25、50、100 mg/kg给药，西地那非组给药剂量为6.3 mg/kg，每日1次，连续干预14 d，对照组及模型组给予等容积蒸馏水。检测各组平均肺动脉压（mPAP）、右心室收缩压（RVSP）、肺组织病理学改变、血清活性氧（ROS）、锰超氧化物歧化酶（Mn-SOD）、丙二醛（MDA）水平及p-ERK1/2、mTOR蛋白表达水平。结果：模型组大鼠mPAP、RVSP水平显著升高（P<0.01），肺小动脉血管壁呈现不规则肥厚，管腔部分狭窄，血清ROS、MDA含量显著升高（P<0.01），Mn-SOD活性显著降低（P<0.01），p-ERK1/2、mTOR表达水平显著升高（P<0.01）。与模型组比较，三七总皂苷各剂量干预后，mPAP、RVSP不同程度下降（P<0.05，P<0.01），肺组织病理性血管重塑减轻；高剂量组ROS、MDA含量显著降低（P<0.01）、Mn-SOD活性升高（P<0.05），中剂量组MDA含量降低（P<0.05）；中剂量组mTOR阳性细胞数降低（P<0.05），高剂量组显著降低（P<0.01）；低剂量组p-ERK1/2蛋白相对表达水平降低（P<0.05），中、高剂量组显著降低（P<0.01），且中、高剂量组表达水平低于低剂量组（P<0.01），高剂量组表达水平低于中剂量组（P<0.05）。结论：三七总皂苷可改善MCT诱导的大鼠PH，其作用机制可能与通过ERK/mTOR信号通路调控氧化应激水平有关。
Abstract:
Objective:To investigate the effect of Panax notoginseng total saponins on oxidative stress in rats with pulmonary hypertension (PH) by regulating ERK/mTOR signaling pathway.Methods:The rat model of PH was induced by monocrotaline (MCT).48 male SPF SD rats were randomly divided into Control group,Model group,Sildenafil group,low-dose Panax notoginseng total saponins group,medium-dose Panax notoginseng total saponins group and high-dose Panax notoginseng total saponins group.The low,medium and high dose groups of Panax notoginseng total saponins were given 25,50 and 100 mg/kg respectively,while the Sildenafil group was given 6.3 mg/kg,once a day for 14 days,and the Control group and the Model group were given the same volume of distilled water.The mean pulmonary artery pressure (mPAP),right ventricular systolic pressure (RVSP),lung histopathological changes,serum levels of reactive oxygen species (ROS),Mn-superoxide dismutase (Mn-SOD) and malondialdehyde (MDA),and the expression levels of p-ERK1/2 and mTOR protein were detected.Results:The levels of mPAP and RVSP in the Model group were significantly increased (P<0.01),the pulmonary arteriole wall showed irregular hypertrophy,the lumen was partially narrowed,quantitative serum assays demonstrated significant upregulation of both ROS and MDA concentrations,the activity of Mn-SOD was significantly decreased (P<0.01),and a significant upregulation (P<0.01) was observed in p-ERK1/2 and mTOR protein levels.Relative to the Model rats,after Panax notoginseng total saponins intervention,mPAP and RVSP decreased in different degrees (P<0.05,P<0.01),and the pathological vascular remodeling level of lung tissue were alleviated.The contents of ROS and MDA in high-dose group decreased significantly (P<0.01),and the activity of Mn-SOD increased (P<0.05),while the content of MDA in medium-dose group decreased (P<0.05).The number of mTOR positive cells in medium-dose group decreased (P<0.05),while that in high-dose group decreased significantly (P<0.01).The relative expression level of p-ERK1/2 protein in low-dose group decreased (P<0.05),and it was significantly decreased in medium and high-dose group (P<0.01),and the expression level in medium-dose and high-dose group was lower than that in low-dose group (P<0.01) and high-dose group was lower than that in medium-dose group (P<0.05).Conclusion:Panax notoginseng total saponins can improve the PH induced by MCT in rats,and the underlying mechanism might be mediated by ERK/mTOR-dependent modulation of oxidative stress.

参考文献/References:

[1]HASSOUN P M.Pulmonary arterial hypertension[J].N Engl J Med,2021,385(25):2361-2376.
[2]陈红阳,王思齐,陈玲,等.有氧运动通过调控SIRT3/FOXO3a信号通路对肺动脉高压大鼠氧化应激水平的影响[J].中国老年学杂志,2025,45(8):1893-1899.
[3]靳朴,武杰.三七总皂苷在心血管疾病中的研究进展[J].中国心血管杂志,2018,23(6):527-530.
[4]JIA Z Z,YAN H F,WANG S,et al.Shufeiya recipe improves monocrotaline-induced pulmonary hypertension in rats by regulating SIRT3/FOXO3a and its downstream signaling pathways[J].Dis Markers,2022,2022:3229888.
[5]闫海峰,王琳,王贤良,等.舒肺压方对野百合碱诱导肺动脉高压模型大鼠肺动脉压及氧化应激的影响[J].中医杂志,2021,62(20):1814-1819.
[6]郭晓燕,毕蓉蓉,张晔敏,等.活血化瘀祛痰法对野百合碱诱导的肺动脉高压大鼠肺血管重构的影响[J].陕西中医,2023,44(1):3-6.
[7]ZOROV D B,JUHASZOVA M,SOLLOTT S J.Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release[J].Physiol Rev,2014,94(3):909-950.
[8]JIA Z Z,WANG S,YAN H F,et al.Pulmonary vascular remodeling in pulmonary hypertension[J].J Pers Med,2023,13(2):366.
[9]陈红阳,贾壮壮,赵磊,等.益气活血组分黄芪甲苷配伍川芎嗪对脑缺血再灌注损伤大鼠神经血管单元的保护作用[J].中国老年学杂志,2022,42(21):5312-5318.
[10]ZHOU W,LIU K,ZENG L,et al.Targeting VEGF-A/VEGFR2 Y949 signaling-mediated vascular permeability alleviates hypoxic pulmonary hypertension[J].Circulation,2022,146(24):1855-1881.
[11]贾壮壮,王贤良,毛静远,等.舒肺压方单煎与合煎的成分差异及对肺动脉高压的影响[J].中西医结合心脑血管病杂志,2024,22(12):2142-2149.
[12]张积思,徐江雁.“肺朝百脉”理论研究评析[J].中华中医药杂志,2020,35(11):5367-5369.
[13]贺玥,冉迅,郎勇,等.三七总皂苷通过PI3K-AKT信号通路对大鼠心房颤动的干预作用[J].国际中医中药杂志,2019,41(5):472-475.
[14]周小雄,叶桃春,罗川晋,等.三七皂苷在JNK介导的低氧高二氧化碳性肺动脉高压模型中的机制探讨[J].中国医药导报,2017,14(18):7-11.
[15]张赛,宋正阳,王淑远,等.三七总皂苷通过Notch3/Hes-1/p27Kip1信号通路抑制低氧性肺动脉高压大鼠肺血管重构[J].中国病理生理杂志,2022,38(2):209-214.
[16]宋正阳,王新雨,田云娜，等.三七总皂苷对肺动脉高压大鼠肺血管重构的影响及其机制[J].中国应用生理学杂志,2022,38(6):650-655.
[17]赵亚男,解琪,贾文旋,等.沙库巴曲缬沙坦联合托伐普坦治疗肺动脉高压所致右心衰竭疗效观察[J].陕西医学杂志,2024,53(12):1680-1684.
[18]SEKAR D.Extracellular vesicles are involved in oxidative stress and mitochondrial homeostasis in pulmonary arterial hypertension[J].Hypertens Res,2021,44(8):1028-1029.
[19]WALTER K.Pulmonary hypertension[J].JAMA,2021,326(11):1116.
[20]蒋沈华,虞坚尔,冯其茂.中药保护线粒体功能在慢性心力衰竭治疗中的应用进展[J].陕西中医,2024,45(7):1006-1009.
[21]BONNET S,BOUCHERAT O.The ROS controversy in hypoxic pulmonary hypertension revisited[J].Eur Respir J,2018,51(3):1800276.
[22]XIAO S L,LIN R K.Polysaccharide of alocasia cucullata exerts antitumor effect by regulating Bcl-2,Caspase-3 and ERK1/2 expressions during long-time AD ministration[J].Chin J Integr Med,2024,30(1):52-61.
[23]WANG H,ZHOU H,REN R,et al.Apolipoprotein E2 inhibits mitochondrial apoptosis in pancreatic cancer cells through ERK1/2/CREB/Bcl-2 signaling[J].Hepatobiliary Pancreat Dis Int,2023,22(2):179-189.
[24]LI Y,GE J P,MA K,et al.The combination of EGCG with warfarin reduces deep vein thrombosis in rabbits through modulating HIF-1α and VEGF via the PI3K/Akt and ERK1/2 signaling pathways[J].Chin J Nat Med,2022,20(9):679-690.
[25]YU M,LIU X,WU H,et al.Small interfering RNA against ERK1/2 attenuates cigarette smoke-induced pulmonary vascular remodeling[J].Exp Ther Med,2017,14(5):4671-4680.
[26]SHIMADA S,FUKAI M,WAKAYAMA K,et al.Hydrogen sulfide augments survival signals in warm ischemia and reperfusion of the mouse liver[J].Surg Today,2015,45(7):892-903.

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备注/Memo

备注/Memo:
国家自然科学基金资助项目（82460923）；云南省基础研究计划项目（202401AZ070001-022）；天津市卫生健康委员会中医中西医结合科研课题（2021048）
更新日期/Last Update: 2025-10-10