运动调节Nrf2/HO-1通路改善HFFC膳食诱导肝细胞氧化应激的作用研究

Effects of exercise regulated the Nrf2/HO-1 pathway on improving HFFC diet-induced oxidative stress in hepatocytes

目的探究自主跑轮运动能否调控Nrf2/HO-1通路影响肝氧化应激从而缓解HFFC膳食诱导的肝脂质沉积。方法将8周龄C57BL/6J小鼠适应性饲养1周后随机分为普通饮食组(NC组,n=10)和高脂肪、果糖和胆固醇饮食组(HFFC组,n=20)。饲养10周后将HFFC组分为安静组(HFFC组,n=10)和HFFC结合运动干预组(HFFC+EX组,n=10)。HFFC+EX组小鼠笼中装有自主跑轮供其自由活动,每天记录跑轮圈数,连续8周。末次干预结束后间隔24 h禁食12 h处死小鼠,取血液和肝进行检测。结果(1)HFFC饮食诱导小鼠的体重、肝重及肝指数显著高于NC组,运动干预后显著降低(P<0.05);(2)与NC组相比,HFFC组小鼠HDL-C和LDL-C显著升高,运动干预8周后LDL-C水平显著降低(P<0.05);(3)HFFC组小鼠肝脂滴面积及肝TG含量显著高于NC组,而HFFC+EX组显著减少(P<0.05);(4)与NC组相比,HFFC组小鼠氧化酶MDA含量显著上升,Nrf2入核及基因表达显著减少,运动干预后SOD和T-AOC活性明显增强,Nrf2入核及基因表达、HO-1和SOD-1的表达水平显著升高(P<0.05);(5)HFFC饮食组小鼠肝细胞凋亡数及CHOP表达水平较NC组显著增加,运动组肝细胞凋亡数、CHOP和Bax/Bcl-2表达水平显著下降(P<0.05)。结论自主跑轮运动可通过调节Nrf2/HO-1通路减轻HFFC膳食诱导的肝脂质沉积,从而缓解肝细胞氧化应激状态,减少细胞凋亡。

Objective To explore whether voluntary wheel running affects liver oxidative stress by regulating the Nrf2/HO-1 pathway,thereby alleviating HFFC diet-related lipid deposition in the liver.Methods Eight-week-old C57BL/6J mice were randomly divided into a normal diet group(NC group,n=10)and high-fat,fructose,and cholesterol diet group(HFFC group,n=20)after 1 week of adaptive feeding.Ten weeks of feeding later,mice in the HFFC group were divided into a quiet group(HFFC group,n=10)and HFFC combined with exercise group(HFFC+EX group,n=10).HFFC+EX group mice were caged with voluntary running wheels for free movement,and the number of running wheels was recorded every day for 8 weeks.After the last treatment,the mice were sacrificed by fasting for 12 hours at an interval of 24 hours,and the blood and liver were collected for analysis.Results(1)Body weight,liver weight,and liver index of mice fed the HFFC diet were significantly higher than those of the NC group,which significantly decreased after exercise(P<0.05).(2)Compared with the NC group,HDL-C and LDL-C in the HFFC group were significantly increased,and the LDL-C level was significantly decreased after 8 weeks of exercise(P<0.05).(3)The liver fat droplet area and liver TG content in the HFFC group were significantly higher than those in the NC group,whereas those in HFFC+EX group were significantly decreased(P<0.05).(4)Compared with the NC group,the content of oxidase MDA in the HFFC group were significantly increased,and nuclear translocation and gene expression of Nrf2 were significantly decreased.After exercise,the activities of SOD and T-AOC were significantly increased,and the nuclear translocation and gene expression of Nrf2 and expression levels of HO-1 and SOD-1 were significantly increased(P<0.05).(5)The number of apoptotic hepatocytes and CHOP expression in the HFFC diet group were significantly higher than those in the NC group,whereas the number of apoptotic hepatocytes,and CHOP and Bax/Bcl-2 expression in the exercise group were significantly lower than those in the NC group(P<0.05).Conclusions Voluntary wheel can alleviate HFFC diet induced liver lipid deposition by regulating the Nrf2/HO-1 pathway,thereby alleviating oxidative stress and reducing apoptosis in liver cells.