姜黄素调控Nrf2信号通路相关蛋白质缓解6周大强度运动致大鼠运动性肝损伤

Curcumin Regulates Proteins Associated with the Nrf2 Signaling Pathway to Alleviate Rat Liver Injury Induced by 6-week High-intensity Exercise

姜黄素(curcumin)作为核因子E2相关因子2(Nrf2)激动剂,对肝损伤的保护作用已在多种疾病模型中得到验证,但姜黄素能否通过调控Nrf2信号通路相关蛋白质缓解大强度运动(high-intensity exercise)所致大鼠肝氧化应激损伤尚不清楚。本研究证明,大鼠训练期间以200 mg/kg/d的5 mL/kg姜黄素灌胃,可缓解6周大强度运动所致大鼠运动性肝损伤。肝组织形态观察及损伤指标检测发现,姜黄素可显著升高鼠肝指数(P<0.05)及肝胆碱酯酶活性(P<0.05),降低血清谷丙转氨酶和谷草转氨酶活性(P<0.01),并改善肝组织形态病理性变化。Nrf2信号通路相关蛋白质的免疫组化检测发现,姜黄素显著上调肝内Nrf2和血红素氧合酶1蛋白质表达水平(P<0.05)。氧化应激指标检测发现,姜黄素显著升高肝超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性(P<0.05或P<0.01),降低肝内丙二醛浓度(P<0.05)。细胞凋亡水平检测及相关蛋白质的免疫组化检测发现,姜黄素显著降低肝细胞凋亡水平(P<0.05),增强抗凋亡蛋白质B淋巴细胞瘤因子-2表达(P<0.05),减弱促凋亡蛋白质Bcl-2相关X蛋白表达(P<0.05),并提高后两者比值(P<0.05)。以上结果表明,6周大强度运动期间进行姜黄素补充,能通过上调Nrf2信号通路相关蛋白质表达,改善相关抗氧化酶活性,进而有效缓解大鼠肝氧化应激状态,抑制肝细胞凋亡,保护肝组织结构和功能正常。

As an agonist of nuclear factor erythroid 2-related factor 2(Nrf2),the protective effect of curcumin on liver injury has been verified in various disease models.However,it is unclear whether curcumin can alleviate oxidative stress injury induced by high-intensity exercise in liver of rats by regulating Nrf2 signaling pathway associated proteins.This study demonstrated that rats fed with curcumin by gavage at a dose of 200 mg/kg/d in a volume of 5 mL/kg during training could alleviate liver injury caused by 6-week high-intensity exercise.The histopathological results and injury indicators of liver showed that curcumin could significantly increase liver index(P<0.05)and liver cholinesterase activity(P<0.05),decrease alanine aminotransferase and aspartate aminotransferase activity(P<0.01),and relieve the histopathological changes.The immunohistochemical detection of Nrf2 signaling pathwayassociated proteins showed that curcumin could significantly increase the expression of Nrf2 and HO-1 in liver(P<0.05).The results of oxidative stress indicators showed that curcumin could significantly increase SOD,CAT and GSH-Px activity(P<0.05 or P<0.01),and decrease MDA concentration(P<0.05)in liver.The apoptosis level detection and immunohistochemical detection of apoptosis-related proteins showed that curcumin could significantly decrease hepatocyte apoptosis(P<0.05)by increasing the expression of Bcl-2(P<0.05)and decreasing the expression of Bax(P<0.05).The above results indicated that supplementation of curcumin during 6-week high-intensity exercise can up-regulate the protein expression of Nrf2 signaling pathway,and enhance the activity of related antioxidant enzymes,thereby alleviating oxidative stress,inhibiting hepatocyte apoptosis and protecting the rat liver structure and function properly.