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姜黄素对过度训练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].

作者信息

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

机构信息

Beijing Union University, Beijing 100023.

Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191.

出版信息

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2019 Nov;35(6):501-505. doi: 10.12047/j.cjap.5872.2019.109.

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.

摘要

目的

通过调节 Kelch 样 ECH 相关蛋白 1(Keap1)-核因子红细胞 2 相关因子 2(Nrf2)-抗氧化反应元件(ARE)信号通路,研究姜黄素减轻大鼠过度训练诱导的氧化应激和脾脏细胞凋亡的机制。

方法

将 7 周龄雄性 Wistar 大鼠分为对照组(C 组,12 只)、过度训练组(OM 组,11 只)、姜黄素+过度训练组(COM 组,14 只)。C 组不进行任何运动干预。OM 组和 COM 组进行 8 周递增负荷游泳训练。训练期间,COM 组大鼠按 200mg/(kg·d)的剂量,以 5ml/kg 的体积通过灌胃给予姜黄素,其他组大鼠给予等体积的溶剂 0.5%羧甲基纤维素钠。末次训练后 24h,称重计算脾脏指数,光镜观察脾脏病理变化,并检测血液和脾脏的生化指标。

结果

光镜下 C 组脾脏结构正常;OM 组脾脏指数显著低于 C 组(P<0.01),病理变化明显;COM 组脾脏指数显著高于 OM 组(P<0.05),组织形态学变化减轻。与 C 组相比,OM 组血清皮质酮(Cor)水平、脾脏细胞凋亡水平、丙二醛(MDA)浓度及脾脏促凋亡蛋白 Bcl-2 相关 X 蛋白(Bax)表达升高(P<0.05 或 P<0.01);体重、血清睾酮(T)、超氧化物歧化酶(SOD)活性、脾脏血红素加氧酶-1(HO-1)及抗凋亡蛋白 B 细胞淋巴瘤-2(Bcl-2)表达降低(P<0.05 或 P<0.01);Nrf2 表达无明显变化(P>0.05)。与 OM 组相比,COM 组体重无明显变化(P>0.05),血清 T 水平、SOD 活性、脾脏 Bcl-2、Nrf2 及 HO-1 表达升高(P<0.05 或 P<0.01);血清 Cor 水平、脾脏细胞凋亡水平、MDA 浓度及 Bax 表达降低(P<0.05 或 P<0.01)。各组 T/Cor 比值变化趋势与睾酮变化一致,Bcl-2/Bax 比值变化趋势与 Bcl-2 变化一致。

结论

8 周递增负荷过度游泳训练加重脾脏细胞凋亡,导致脾脏病理变化和功能障碍。姜黄素可上调 Nrf2 和 HO-1 表达,减轻过度训练诱导的氧化应激,增强 Bcl-2 表达,减弱 Bax 表达,从而抑制大鼠脾脏过度凋亡,保护脾脏结构和功能。

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