姜黄素对过度训练所致大鼠心肌细胞凋亡的保护作用

目的:研究姜黄素缓解过度训练所致的氧化应激,抑制大鼠心肌细胞凋亡的保护作用。方法:60只7周龄SPF级雄性Wistar大鼠经适应性饲养及训练后随机分为对照组(C组,12只)、过度训练组(OM组,24只)、姜黄素+过度训练组(COM组,24只)。C组不进行任何训练,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)剂量姜黄素进行灌胃,灌胃体积5 mL/kg,其余两组灌胃等体积0.5%羧甲基纤维素纳。末次训练后24 h,光镜观察心肌组织病理学改变,检测血清睾酮(T)、皮质酮(Cor)、心肌肌钙蛋白I(cTnI)浓度,以及心肌组织凋亡水平和核因子E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)、B淋巴细胞瘤因子-2(Bcl-2)、Bcl-2相关X蛋白(Bax)表达,同时测定心肌组织总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)活性以及丙二醛(MDA)浓度。结果:8周递增负荷游泳训练后,光镜下C组大鼠心肌组织结构正常;OM组出现组织病理学改变;COM组较OM组明显减轻。与C组比较,OM组血清Cor、cTnI、心肌细胞凋亡水平和促凋亡蛋白Bax表达水平及心肌MDA浓度均升高(p<0.01),血清T水平、心肌T-AOC和SOD活性(p<0.01)、心肌HO-1及抗凋亡蛋白Bcl-2表达水平(p<0.05)降低;心肌Nrf2表达水平无显著变化(p>0.05)。与OM组比较,COM组血清Cor、心肌细胞凋亡水平、Bax表达水平(p<0.01)和血清cTnI水平、心肌MDA浓度(p<0.05)降低,血清T水平、心肌Nrf2和Bcl-2表达水平、心肌T-AOC和SOD活性(p<0.01)、心肌HO-1(p<0.05)升高。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: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,从而增加Bcl-2表达,减少Bax表达,抑制大鼠心肌细胞凋亡,保护心脏组织结构和功能正常。

Protective Effect of Curcumin on Cardiomyocyte Apoptosis Induced by Overtraining in Rats

Objective:To study the protective effect of curcumin on oxidative stress and inhibition of cardiomyocyte apoptosis induced by overtraining in rats. Methods:Sixty male Wistar rats of 7 weeks old were randomly divided into control group(C group,12),overtraining group(OM group,24),curcumin+overtraining group(COM group,24)after adaptive feeding and training. The C Group did not undergo any training. Rats in OM and COM group underwent 8-week incremental load swimming training. During the training,the COM group was given 200 mg/(kg·d)of curcumin in the volume as 5 mL/kg,and the other groups were given an equal volume of 0.5% carboxymethylcellulose. 24 hours after the last training,myocardial histopathological changes were observed by light microscopy;serum testosterone(T),corticosterone(Cor)and cardiac troponin I(cTnI),cardiomyocyte apoptosis level,the expression level of nuclear factor E2 related factor 2(Nrf2),heme oxygenase-1(HO-1),B cell lymphoma-2 protein(Bcl-2)and Bcl-2 related X protein(Bax)in myocardium were detected;myocardial total antioxidant capacity(T-AOC),superoxide dismutase(SOD)activity,malondialdehyde(MDA)concentration were also detected. Results:The results showed that after 8-week incremental load swimming training,the myocardial tissue structure of the C group was normal under light microscope;histopathological changes were observed in the OM group;the COM group was relieved compared with the OM group. Compared with the C group,serum corticosterone and cTnI,cardiomyocyte apoptosis level,the expression level of proapoptotic Bax,MDA concentration in OM group were increased(p<0.01);serum testosterone,myocardial T-AOC and SOD activity(p<0.01),the expression level of HO-1 and anti-apoptotic Bcl-2(p<0.05)were lower;Nrf2 expression level did not change significantly(p>0.05). Compared with the OM group,serum corticosterone,cardiomyocyte apoptosis level,the expression of Bax(p<0.01),serum cTnI,myocardial MDA concentration(p<0.05)were decreased in the COM group;serum testosterone,the expression levels of Nrf2 and Bcl-2,myocardial T-AOC and SOD activity(p<0.01),the expression levels of HO-1(p<0.05)were increased. The trends of T/Cor and Bcl-2/Bax between groups were consistent with the changes of T and Bcl-2,respectively. Conclusion:Curcumin can up-regulates expression of Nrf2 and HO-1,effectively alleviates oxidative stress induced by overtraining,thereby increasing Bcl-2 expression,decreasing Bax expression,inhibiting cardiomyocyte apoptosis and protecting cardiac tissue structure and function properly.