基于核转录因子E2相关因子2/抗氧化反应元件信号通路探讨姜黄素减轻老龄大鼠肺缺血再灌注损伤的效果

Investigation on Effect of Curcumin on Lung Ischemia-Reperfusion Injury in Aged Rats Based on Nuclear Factor E2-Related Factor 2/Antioxidant Response Element Signaling Pathway

目的:基于核转录因子E2相关因子2(Nrf2)/抗氧化反应元件信号通路探讨姜黄素减轻老龄大鼠肺缺血再灌注损伤的效果。方法:将60只清洁级Wistar老龄大鼠分成3组。对照组、模型组每天腹腔注射0.9%氯化钠(3 mL/kg),姜黄素组每天腹腔注射姜黄素,持续7 d。模型组、姜黄素组大鼠于第7天注射相应药物60 min后建立肺缺血再灌注模型;随后获取肺组织,测定肺/体质量比值及肺损伤评分,并测定肺组织中Nrf2、血红素加氧酶-1(HO-1)mRNA、蛋白表达水平及丙二醛(MDA)、超氧化物歧化酶(SOD)、一氧化氮(NO)、白细胞介素-6(IL-6)、白细胞介素-2(IL-2)、肿瘤坏死因子-α(TNF-α)水平。结果:与对照组比较,模型组肺/体质量比值、肺损伤评分、肺组织Nrf2 mRNA、蛋白表达水平及MDA、IL-6、NO、TNF-α、IL-2表达水平升高(P<0.05),HO-1 mRNA、蛋白表达水平及SOD表达水平降低(P<0.05);与模型组比较,姜黄素组肺/体质量比值、肺损伤评分、肺组织Nrf2 mRNA、蛋白表达水平及MDA、IL-6、NO、TNF-α、IL-2表达水平降低(P<0.05),HO-1 mRNA、蛋白表达水平及SOD表达水平升高(P<0.05)。结论:姜黄素抑制Nrf2表达激活抗炎、抗氧化途径,使炎症因子与氧化应激产物水平下降,以此对老龄大鼠肺缺血再灌注损伤起保护作用。

Objective:To investigate the effect of curcumin on lung ischemia-reperfusion injury in aged rats based on nuclear factor E2-related factor 2(Nrf2)/antioxidant response element signaling pathway.Methods:A total of 60 clean Wistar aged rats were divided into three groups.The control group and the model group were intraperitoneally injected with 0.9%of sodium chloride(3 mL/kg)every day,and the curcumin group was intraperitoneally injected with curcumin every day.The injection lasted for seven days.Lung ischemia-reperfusion models were established in the model group and the curcumin group 60 minutes after the injection with corresponding drugs on the seventh day;lung tissue was then obtained to measure the lung/body weight ratio and lung injury scores as well as the mRNA and protein expressions of Nrf2 and heme oxygenase-1(HO-1),and the levels of malondialdehyde(MDA),superoxide dismutase(SOD),nitric oxide(NO),interleukin-6(IL-6),interleukin-2(IL-2)and tumor necrosis factor-α(TNF-α)in lung tissue.Results:The lung/body weight ratio,the lung injury scores as well as the mRNA and protein expressions of Nrf2 and the expression levels of MDA,IL-6,NO,TNF-α and IL-2 in lung tissue in the model group were increased when compared with those in the control group(P<0.05),and the mRNA and protein expressions of HO-1 as well as the expression level of SOD were decreased(P<0.05);the lung/body weight ratio,the lung injury scores as well as the mRNA and protein expressions of Nrf2 and the expression levels of MDA,IL-6,NO,TNF-α and IL-2 in lung tissue in the curcumin group were decreased when compared with those in the model group(P<0.05),and the mRNA and protein expressions of HO-1 as well as the expression level of SOD were increased(P<0.05).Conclusion:By inhibiting Nrf2 expression and activating anti-inflammatory and antioxidant pathways,curcumin decreases the levels of inflammatory factors and oxidative stress products,so as to play a protective role in aged rats with lung ischemia-reperfusion injury.