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*

doi:10.12047/j.cjap.5872.2019.109

摘要/Abstract

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, 脾

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

中图分类号:

G804.7

周海涛, 曹建民, 胡戈, 张静, 郭娴, 牛衍龙, 王安琪, 杜堃, 魏江山, 关云鹏, 邵芙蓉, 赵卓. 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^*[J]. 中国应用生理学杂志, 2019, 35(6): 501-505.

ZHOU Hai-tao, CAO Jian-min, HU Ge, ZHANG Jing, GUO Xian, NIU Yan-long, WANG An-qi, DU Kun, WEI Jiang-shan, GUAN Yun-peng, SHAO Fu-rong, ZHAO Zhuo. Regulatory effects of curcumin on spleen apoptosis in overtraining rats and its mechanism[J]. CJAP, 2019, 35(6): 501-505.

参考文献

[1] 王雪芹, 郝选明. 长期递增负荷运动对大鼠脾淋巴细胞增殖活性、凋亡及凋亡相关基因表达的影响[J]. 中国体育科技, 2013, 49(6): 100-104.
[2] 龙杰, 王羽, 刘晓翠, 等. 氧化应激对原代培养乳鼠心房肌细胞中内质网应激及凋亡因子的影响[J]. 中国应用生理学杂志, 2017, 33(2): 185-188.
[3] Niture SK, Jaiswal AK. Nrf2 protein up-regulates antiapoptotic protein Bcl-2 and prevents cellular apoptosis[J]. J BiolChem, 2012, 287(13): 9873-9886.
[4] 徐菲菲, 缪成锋, 池琛, 等. 姜黄素及其类似物J7对2型糖尿病大鼠睾丸氧化应激损伤的干预作用[J]. 中国应用生理学杂志, 2019, 35(2): 145-149.
[5] 胡戈, 曹卉, 周海涛, 等. 姜黄素对过度训练大鼠肾脏细胞凋亡的调控作用及其机制[J]. 中国应用生理学杂志, 2018, 34(6): 513-518.
[6] 郭爱民, 李亚俊, 曹卉, 等. 姜黄素对过度训练所致大鼠心肌细胞凋亡的保护作用[J]. 食品工业科技, 2019, 40(15): 304-310.
[7] Wang J, Cao JM, Huang AL, et al. Effect of haematococcuspluvialis on exercise-related renal ischemia-reperfusion injury and ECM expression[J]. Int J Clin Exp Med, 2016, 9(4): 7127-7136.
[8] 牛爱丽. 姜黄素对力竭运动大鼠肾损伤的保护作用及其机制的研究[D]. 长沙: 湖南师范大学, 2012.
[9] 李园, 刘文杰, 杨宁, 等. 原花青素对大负荷运动模型大鼠脾细胞自由基代谢及凋亡蛋白的影响[J]. 中国组织工程研究, 2015, 19(49): 8026-8031.
[10]李丽, 常波. 过度训练动物模型制备的研究进展[J]. 沈阳体育学院学报, 2011, 30(5): 77-82.
[11]Hybertson BM, Gao B, Bose SK, et al. Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation[J]. Mol Aspects Med, 2011, 32(4-6): 234-246.
[12]Paine A, Eiz-Vesper B, Blasczyk R, et al. Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential[J]. Biochem Pharmacol, 2010, 80(12): 1895-1903.
[13]胡戈, 曹建民, 周海涛, 等. 虾青素介导Nrf2信号通路减轻大强度运动诱导大鼠心肌细胞的凋亡[J]. 食品工业科技, 2018, 40(8): 266-271.
[14]Ola MS, Nawaz M, Ahsan H. Role of Bcl-2 family proteins and caspases in the regulation ofapoptosis[J]. Mol Cell Biochem, 2011, 351(1-2): 41-58.
[15]Zhang J, Su L, Ye Q, et al. Discovery of a novel Nrf2 inhibitor that induces apoptosis of human acute myeloid leukemia cells[J]. Oncotarget, 2017, 8(5): 7625-7636.
[16]Takahashi M, Suzuki K, Kim HK, et al. Effects of curcumin supplementation on exercise-induced oxidative stress in humans[J]. Int J Sports Med, 2014, 35(6): 469-475.
[17]Shehzad A, Ha T, Subhan F, et al. New mechanisms and the anti-inflammatory role of curcumin in obesity and obesity-related meta-bolicdiseases[J]. Eur J Nutr, 2011, 50(3): 151-161.
[18]贺许良. 姜黄素对脾放射损伤的影响及其机制研究[D]. 衡阳: 南华大学, 2014.

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^*

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

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