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

目的：探讨姜黄素对过度训练所致大鼠氧化应激、肾脏细胞凋亡的作用及其机制。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%浓度羧甲基纤维素纳。末次训练后24 h,光镜观察肾脏组织病理学改变,取血液、肾脏组织检测相关生化指标。结果：8周递增负荷游泳训练后,光镜下C组大鼠肾脏组织结构正常;OM组出现组织病理学改变;COM组较OM组减轻。与C组比较,OM组血清皮质酮（Cor）、肌酐（Cr）和尿素氮（BUN）水平均升高（P<0.01）,睾酮（T）水平降低（P<0.01）;肾脏核因子E2相关因子2（Nrf2）表达水平无显著变化（P>0.05）,血红素氧合酶1（HO-1）表达水平降低（P<0.05）,总抗氧化能力（T-AOC）和超氧化物歧化酶（SOD）活性降低（P<0.01）,丙二醛（MDA）浓度升高（P<0.01）;肾脏细胞凋亡水平升高（P<0.01）,肾脏抗凋亡蛋白B淋巴细胞瘤因子-2（Bcl-2）表达减弱（P<0.01）,促凋亡蛋白Bcl-2相关X蛋白（Bax）表达增强（P<0.01）。与OM组比较,COM组血清Cor水平（P<0.01）降低,T水平升高（P<0.01）,Cr和BUN水平均降低（P<0.05）;肾脏Nrf2和HO-1表达增强（P<0.05）,T-AOC和SOD活性升高（P<0.01）,MDA浓度降低（P<0.05）;肾脏细胞凋亡水平降低（P<0.05）,Bcl-2表达增强（P<0.05）,Bax表达减弱（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周递增负荷游泳训练引发大鼠过度训练,氧化应激加剧并加速肾脏细胞凋亡,肾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,有效缓解过度训练引发的氧化应激,从而增强Bcl-2表达,减弱Bax表达,抑制大鼠肾脏细胞凋亡,保护肾脏组织结构和功能正常。

Regulatory effect of curcumin on renal apoptosis and its mechanism in overtraining rats

Objective: To study the effects and mechanisms of curcumin alleviating oxidative stress induced by overtraining and inhibiting renal apoptosis in rats. 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). Group C did not undergo any exercise intervention. Rats in OM group and COM group underwent 8-week incremental load swimming training. During the training, the COM group was treated with curcumin at the dose of 200 mg/(kg·d) in the volume as 5 ml/kg by intragastric administration, and the other groups was treated with an equal volume of 0.5% carboxymethylcellulose. Twenty-four hours after the last training, renal histopathological changes were observed by light microscopy, related biochemical indicators in blood and renal tissue were detected. Results: The results showed that after 8 weeks of incremental load swimming training, the renal tissue structure of group C was normal under light microscope; histopathological changes were observed in OM group; COM group was significantly relieved compared with OM group. Compared with group C, serum levels of corticosterone (Cor), creatinine (Cr) and blood urea nitrogen (BUN) in OM group were increased (P<0.01), serum level of testosterone (T) was lower (P<0.01); the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) was not changed significantly (P>0.05), while the expression of heme oxygenase-1 (HO-1) was decreased (P<0.05), total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity were decreased (P<0.01), malondialdehyde (MDA) concentration was increased (P<0.01); the renal apoptosis was increased (P<0.01), the expression of anti-apoptotic B cell lymphoma-2 protein (Bcl-2) was decreased (P<0.01), and the expression of proapoptotic Bcl-2 associated X protein (Bax) was increased (P<0.01). Compared with the OM group, Cor level was decreased (P<0.01) in the COM group, T level was increased (P<0.01), Cr and BUN levels were lower (P<0.05); the expression of Nrf2 and HO-1 were increased (P<0.05), T-AOC and SOD activity were increased (P<0.01), MDA concentration was decreased (P<0.05); the renal apoptosis was decreased (P<0.05), the expression of Bcl-2 was increased (P<0.05), and the expression of Bax was decreased (P<0.01). The trend of testosterone/corticosterone ratio between groups was consistent with testosterone change, and the change trend of Bcl-2/Bax ratio was consistent with the change of Bcl-2. Conclusion: The 8-week incremental load swimming training triggered excessive training in rats, aggravated oxidative stress and accelerated renal apoptosis, leading to pathological changes and dysfunction of kidney. Curcumin can up-regulate expression of Nrf2 and HO-1, effectively alleviates oxidative stress induced by overtraining, thereby increasing Bcl-2 expression, decreasing Bax expression, inhibiting renal apoptosis and protecting renal tissue structure and function properly.