目的 研究辣木叶提取物（Moringa oleifera leaves extract,MLE）在高原低氧环境下的抗疲劳作用,并探讨相关的机制。方法 （1）将雄性昆明小鼠随机分为低氧游泳对照（HSC）、MLE低剂量（MLEL）及高剂量（MLEH）3组,每组8只,分别灌胃蒸馏水、1000 、2000 mg/（kg·bw）的MLE,每日一次。灌胃15 d后,在低压氧舱（模拟4000 m海拔高度）内按小鼠体质量的5%尾部负重游泳,记录力竭游泳时间。（2）将雄性昆明小鼠随机分为常氧对照（NC）、低氧对照（HC）、HSC组及MLE4组,每组12只,MLE组灌胃2000 mg/（kg·bw）的MLE,其他组灌胃蒸馏水,每日一次,灌胃15d后,在低压氧舱（模拟4000 m海拔高度）内进行90 min非负重游泳实验。取血液、肝脏及骨骼肌组织测定各项指标。结果 与HSC组相比,MLEH组小鼠的力竭游泳时间显著延长（P<0.05）。与NC组相比,HSC组疲劳相关指标血清乳酸（LA）、血尿素氮（BUN）及骨骼肌氧化应激相关指标丙二醛（MDA）、活性氧（ROS）水平显著升高; CCAAT/增强子结合蛋白同源蛋白（CHOP）、葡萄糖调节蛋白78（GRP78/Bip）等内质网应激指标和凋亡指标胱天蛋白酶3（Caspase-3）的水平显著升高（P<0.05）;而血糖（Glu）、肌糖原（MG）及肝糖原（LG）水平,骨骼肌超氧化物歧化酶（SOD）活性显著降低（P<0.05）。与HC组相比,HSC组血清BUN水平,骨骼肌ROS和细胞凋亡率、GRP78和Caspase-3表达显著升高,而Glu、MG、LG及骨骼肌GSH水平、SOD及GSH-Px的活性显著降低（P<0.05）。与HSC组相比,MLE组血清LA、BUN及骨骼肌MDA水平显著降低,骨骼肌ROS及细胞凋亡率显著降低,Glu、MG、LG及骨骼肌GSH水平显著升高、SOD和GSH-Px活性显著升高,GRP78/Bip、CHOP及Caspase-3表达显著降低（P<0.05）。结论 在高原低氧环境下,MLE可通过减少代谢产物累积、减轻氧化应激、缓解内质网应激发挥抗疲劳作用。
Abstract
Objective To investigate anti-fatigue effect of the Moringa oleifera leaves extract (MLE), and explore the mechanisms in mice exposed to hypoxic environment. Methods (1) Male Kunming mice were randomly divided into hypoxia swimming control (HSC) group, MLE low- and high-dose groups. The control group was given distilled water, and the MLE low- and high-dose groups were intragastrically given MLE at doses of 1000mg/kg and 2000mg/kg per day. After 15d of gavage, exhaustive swimming experiment was performed in a hypobaric hypoxic chamber which simulated an altitude of 4000 meters, and survival time was recorded. (2) Male Kunming mice were randomly divided into normal control (NC) group, hypoxia control (HC) group, HSC group and MLE group. The MLE group was intragastrically administrated MLE at dose of 2000 mg/kg per day. The other three groups were given distilled water. After 15d of gavage, a 90-min swimming test was performed in a hypobaric hypoxic chamber which simulated an altitude of 4000 meters. Serum, liver and muscle tissues were taken after the test, and related parameters were determined. Results Compared with the HSC group, the survival time of MLE high-dose group was prolonged significantly（P<0.05）. Compared with the NC group, the levels of serum lactic acid (LA), blood urea nitrogen (BUN), and the content of malondialdehyde (MDA) in skeletal muscle were increased. The levels of reactive oxygen species (ROS), CHOP and GRP78 (endoplasmic reticulum stress markets) and Caspase-3 (apoptosis indicator) in skeletal muscles were increased significantly（P<0.05）, while the levels of Glu, muscle glycogen (MG) and liver glycogen (LG) and activities of SOD in skeletal muscles were significantly decreased in the HSC group（P<0.05）. Compared with the HC group, the levels of BUN, ROS and apoptosis ratio in skeletal muscles, and the expression of GRP78 and Caspase-3 in skeletal muscles were increased significantly in the HSC group, while the levels of blood Glu, MG and LG, content of GSH in skeletal muscles, and activities of SOD and GSH-Px in skeletal muscles were decreased significanty in the HSC group（P<0.05）. Compared with the HSC group, the levels of LA and BUN in serum, MDA, ROS and apoptosis in skeletal muscles, and the expressions of GRP78, CHOP and Caspase-3 were decreased remarkably in the MLE group. The levels of Glu, MG and LG, the content of GSH in skeletal muscles, and activities of SOD and GSH-Px in skeletal muscles were increased significantly（P<0.05）. Conclusion Under hypoxic environment, MLE exerts anti-fatigue action by reducing metabolites accumulation, relieving oxidative stress, and alleviating endoplasmic reticulum stress.
关键词
辣木叶提取物 /
低氧 /
疲劳 /
小鼠 /
氧化应激 /
内质网应激
Key words
Moringa oleifera leaves extract /
hypoxia /
fatigue /
oxidative stress /
endoplasmic reticulum stress /
mouse
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参考文献
[1] Chapman RF.The individual response to training and competition at altitude[J]. Br J Sports Med,2013,47:i40–i44.
[2] 杨海平. 低氧、运动对大鼠骨骼肌细胞凋亡及bcl-2、bax表达的影响[D]. 北京:北京体育大学, 2005.
[3] 张卫花, 康龙丽. 高原习服的重要性及研究现状[J]. 国外医学(医学地理分册), 2018,39:108–112.
[4] 王亚雯. 山葵树叶抗疲劳作用及相关机制研究[D]. 南宁:广西医科大学, 2018.
[5] 秦宁宁, 谢华, 赵安鹏, 等. 高原低氧环境下红景天苷对小鼠运动耐力的影响[J]. 浙江大学学报(医学版), 2022,51:397–404.
[6] 杨嵘, 张连成, 陶慧敏, 等. 吡咯喹啉醌对模拟急性高原暴露小鼠的抗缺氧和抗疲劳作用的研究[J]. 营养学报, 2020,42:602–606.
[7] Gao C, Yang BN, Li YR, et al. A monocarboxylate transporter-dependent mechanism confers resistance to exercise-induced fatigue in a high-altitude hypoxic environment[J]. Sci Rep,2023,13:2949.
[8] 王艺博, 王峰, 肖志勇, 等. 大株红景天胶囊提高小鼠耐常压缺氧能力和抗疲劳作用[J]. 中国药理学与毒理学杂志, 2021,35:420–426.
[9] Chobanyan-Jurgens K, Scheibe RJ, Potthast AB, et al. Influences of hypoxia exercise on whole-body insulin sensitivity and oxidative metabolism in older indivi-duals[J]. J Clin Endocrinol Metab, 2019,104: 5238–5248.
[10] 罗晓红, 周珺, 贾正平, 等. 模拟高原低氧应激环境下大鼠内分泌代谢的变化研究[J]. 西北国防医学杂志, 2014, 35:304–308.
[11] Morales-Alamo D, Calbet J.AMPK signaling in skeletal muscle during exercise: role of reactive oxygen and nitrogen species[J]. Free Radic Biol Med, 2016, 98:68–77.
[12] Liu Z, Nie R, Liu Y, et al. Effects of total soy saponins on free radicals in the quadriceps femoris, serum testosterone, LDH, and BUN of exhausted rats[J]. J Sport Health Sci, 2017,6:359–364.
[13] Leon-Lopez J, Calderon-Soto C, Perez-Sanchez M, et al. Oxidative stress in elite athletes training at moderate altitude and at sea level[J]. Eur J Sport Sci, 2018, 18:832–841.
[14] Wu X, Gu W, Lu H, et al. Soluble receptor for advanced glycation end product ameliorates chronic intermittent hypoxia induced renal injury, inflammation, and apop-tosis via P38/JNK signaling pathways[J]. Oxid Med Cell Longev, 2016,2016:1015390.
[15] Chen X, Cubillos-Ruiz JR.Endoplasmic reticulum stress signals in the tumour and its microenvironment[J]. Nat Rev Cancer, 2021,21:71–88.
[16] Malhotra J D, Miao H, Zhang K, et al. Antioxidants reduce endoplasmic reticulum stress and improve protein secretion[J]. Proc Natl Acad Sci USA, 2008,105:18525–18530.
[17] Marciniak SJ, Chambers JE, Ron D.Pharmacological targeting of endoplasmic reticulum stress in disease[J]. Nat Rev Drug Discov,2022,21:115–140.
[18] 杨力源, 张业廷, 李垂坤, 等. 有氧运动训练影响阿尔茨海默症小鼠海马Notch1、Caspase-3的表达[J]. 中国组织工程研究,2024,28:4113–4120.
[19] 李晨晨, 吴玲玲, 史新娥. 骨骼肌中肌浆网/内质网钙ATP酶的功能及其作用机制[J]. 中国生物化学与分子生物学报, 2022,38:981–989.
[20] 周伟, 刘能, 林丽静, 等. 辣木叶乙醇提取物的抗氧化活性研究[J]. 现代食品科技,2017,33:149–156.
