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中国应用生理学杂志 ›› 2019, Vol. 35 ›› Issue (6): 501-505.doi: 10.12047/j.cjap.5872.2019.109

• 研究论文 • 上一篇    下一篇

姜黄素对过度训练致大鼠脾脏细胞凋亡的调控作用及其机制*

周海涛1,2, 曹建民3, 胡戈3, 张静1,2, 郭娴3, 牛衍龙4, 王安琪1, 杜堃1, 魏江山1, 关云鹏1, 邵芙蓉1, 赵卓1,2△   

  1. 1. 北京联合大学, 北京 100023;
    2. 北京联合大学生物活性物质与功能食品北京市重点实验室, 北京 100191;
    3. 北京体育大学, 北京 100084;
    4. 赣南医学院, 江西 赣州 341000
  • 收稿日期:2019-05-06 出版日期:2019-11-28 发布日期:2020-04-02
  • 通讯作者: 北京市朝阳区协同创新项目(CYXC1817);北京市高等学校高水平人才交叉培养“实培计划”项目;北京联合大学“启明星”大学生科技创新创业项目(201911417034,201911417SJ155)

Regulatory effects of curcumin on spleen apoptosis in overtraining rats and its mechanism

ZHOU Hai-tao1,2, CAO Jian-min3, HU Ge3, ZHANG Jing1,2, GUO Xian3, NIU Yan-long4, WANG An-qi1, DU Kun1, WEI Jiang-shan1, GUAN Yun-peng1, SHAO Fu-rong1, ZHAO Zhuo1,2△   

  1. 1. Beijing Union University, Beijing 100023;
    2. Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191;
    3. Beijing Sport University, Beijing 100084;
    4. Gannan Medical University, Ganzhou 341000, China
  • Received:2019-05-06 Online:2019-11-28 Published:2020-04-02

摘要: 目的:研究姜黄素调控Keap1-Nrf2-ARE信号通路缓解大鼠过度训练所致脾脏氧化应激及细胞凋亡机制。方法:7周龄SPF级雄性Wistar大鼠分为对照组(C组,n=12)、过度训练组(OM组,n=11)、姜黄素+过度训练组(COM组,n=14)。C组不进行任何运动干预,OM组、COM组大鼠进行8周递增负荷游泳训练。训练期间,COM组以200 mg/(kg·d)、5 ml/kg姜黄素进行灌胃,其他组灌胃等体积0.5 %羧甲基纤维素纳助溶剂。末次训练后24 h,称重计算脾脏指数,光镜观察脾脏组织病理学改变,取血液、脾脏组织检测相关生化指标。结果:C组大鼠脾脏组织结构正常;OM组较C组脾脏指数极显著降低(P<0.01),并出现明显病理学改变;COM组较OM组脾脏指数显著升高(P<0.05),且组织形态学改变有所改善。与C组比较,OM组血清皮质酮(Cor)浓度和脾脏细胞凋亡水平、丙二醛(MDA)浓度均升高,促凋亡蛋白Bcl-2相关X蛋白(Bax)表达增强(P<0.05或P<0.01);体重、血清睾酮(T)水平及脾脏超氧化物歧化酶(SOD)活性降低,脾脏血红素氧合酶1(HO-1)、抗凋亡蛋白B淋巴细胞瘤因子-2(Bcl-2)表达减弱(P<0.05或P<0.01);脾脏核因子E2相关因子2(Nrf2)表达水平无显著变化(P>0.05)。与OM组比较,COM组体重无显著变化(P>0.05);血清T浓度升高,脾脏SOD活性升高,Bcl-2、Nrf2和HO-1表达增强(P<0.05或P<0.01);血清Cor浓度及脾脏MDA浓度、细胞凋亡水平、Bax表达均降低或减弱(P<0.05或P<0.01);组间T/Cor比值变化趋势与T变化相一致,Bcl-2/Bax比值变化趋势与Bcl-2变化相一致。结论:8周递增负荷过度游泳训练引发脾脏细胞凋亡加剧,脾脏组织发生病理改变及功能异常。姜黄素通过上调Nrf2、HO-1蛋白表达,在一定程度上缓解过度训练引发的氧化应激,增强抑凋亡蛋白Bcl-2表达,减弱促凋亡蛋白Bax表达,改善大鼠脾脏细胞过度凋亡,保护脾脏组织结构和功能正常。

关键词: 姜黄素, 过度训练, 凋亡, Nrf2, 大鼠,

Abstract: Objective: To study the mechanisms of curcumin alleviating oxidative stress and spleen apoptosis induced by overtraining in rats by regulating Kelch-like ECH-associated protein-1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway. Methods: Male Wistar rats of 7 weeks old were divided into control group (C group, 12), overtraining group (OM group, 11), curcumin + overtraining group (COM group, 14). The C Group did not undergo any exercise intervention. The OM and COM group underwent 8-week incremental load swimming training. During the training, rats in the COM group were treated with curcumin at the dose of 200 mg/(kg·d) in the volume of 5 ml/kg by gavage, and rats in the other groups were given an equal volume of solvent, 0.5% sodium carboxymethylcellulose. Twenty-four hours after the last training, the spleen index was calculated by weighing, the pathological changes of the spleen were observed by light microscopy, and the biochemical indicators of blood and spleen were detected. Results: The spleen structure of C group was normal under light microscope; the spleen index of OM group was significantly lower than that of C group (P<0.01) and pathological changes were obvious; the spleen index of COM group was significantly higher than that of OM group (P<0.05) and histomorphological changes were relieved. Compared with C group, in OM group, serum corticosterone (Cor) level, spleen apoptosis level, malondialdehyde (MDA) concentration and the expression of proapoptotic Bcl-2 associated X protein (Bax) in spleen were increased (P<0.05 or P<0.01); the body weight, serum testosterone (T), superoxide dismutase (SOD) activity, the expressions of heme oxygenase-1 (HO-1) and anti-apoptotic B cell lymphoma-2 protein (Bcl-2) in spleen were decreased (P<0.05 or P<0.01); the expression of Nrf2 was not changed significantly (P> 0.05). Compared with OM group, in COM group, there were no significant changes in body weight (P>0.05), serum T level, SOD activity, the expressions of Bcl-2, Nrf2 and HO-1 in spleen were increased (P<0.05 or P<0.01); serum Cor level, spleen apoptosis level, MDA concentration and the expression of Bax were decreased (P<0.05 or P<0.01). The change trend of T/Cor ratio between groups was consistent with the change of testosterone, and the change trend of Bcl-2/Bax ratio was consistent with the change of Bcl-2. Conclusion: The 8-week incremental load excessive swimming training aggravated spleen apoptosis, led to pathological changes and dysfunction of spleen. Curcumin can up-regulate expression of Nrf2 and HO-1, alleviate oxidative stress induced by overtraining, enhance Bcl-2 expression and attenuate Bax expression, thereby inhibiting excessive spleen apoptosis of rats, protecting the structure and function of spleen.

Key words: curcumin, overtraining, apoptosis, Nrf2, rat, spleen

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