白杨素对心肌缺血再灌注损伤大鼠Nrf2/HO-1信号通路的影响

目的研究白杨素对心肌缺血再灌注损伤大鼠核因子E2相关因子2(Nrf2)/血红素加氧酶-1(HO-1)信号通路的影响。方法依随机数字法将60只清洁级雄性SD大鼠分为假手术组、模型组、雷米普利组和白杨素低、中、高剂量组,每组10只。雷米普利组给予雷米普利1.0 mg/(kg·d)灌胃,白杨素低、中、高剂量组分别给予白杨素10 mg/(kg·d)、20 mg/(kg·d)和40 mg/(kg·d)灌胃,假手术组和模型组给予等量蒸馏水灌胃。灌胃2周后,除假手术组外,其余组构建心肌缺血再灌注损伤模型。处死大鼠,HE染色观察心肌组织病理变化,检测血清心肌酶肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、肌钙蛋白I(cTnI)]、血液和心肌组织中氧化和抗氧化指标丙二醛(MDA)、超氧化物歧化酶(SOD)和活性氧簇(ROS)]水平以及心肌组织中Nrf2、HO-1蛋白及mRNA表达量。结果假手术组大鼠心肌纤维排列整齐,模型组明显断裂,各药物组相较于模型组明显好转。模型组大鼠血清CK、CK-MB、LDH、cTnI水平及血液和心肌组织中MDA、ROS水平均明显高于假手术组(P均<0.05),各药物组上述指标水平均明显低于模型组(P均<0.05);模型组大鼠血液和心肌组织中SOD水平均明显低于假手术组(P均<0.05),各药物组上述指标水平均明显高于模型组(P均<0.05)。模型组大鼠心肌组织中Nrf2和HO-1蛋白及mRNA表达量均明显高于假手术组(P均<0.05),各药物组上述指标表达量均明显高于模型组(P均<0.05)。结论白杨素可能通过调控Nrf2/HO-1信号通路,提高心肌抗氧化能力而抑制再灌注带来的心肌损伤。

Effects of chrysin on Nrf2/HO-1 signaling pathway in rats with myocardial ischemia-reperfusion injury

Objective It is to study the effect of chrysin on the nuclear factor E2 related factor 2(Nrf2)/heme oxygenase-1(HO-1)(Nrf2/HO-1)signaling pathway in rats with myocardial ischemia-reperfusion injury.Methods According to the random number method,60 clean-grade male SD rats were divided into sham operation group,model group,ramipril group and chrysin low,medium and high dose groups,each group with 10 rats.The ramipril group was given ramipril 1.0 mg/(kg·d)by gavage,and the low,medium,and high-dose groups of chrysin were respectively given chrysin 10 mg/(kg·d),20 mg/(kg·d).and 40 mg/(kg·d)by gavage,the sham operation group and model group were given the same amount of distilled water by gavage.After 2 weeks of intragastric administration,except for the sham operation group,the rest rats of the other groups were established models of myocardial ischemia reperfusion injury.After modeling,the rats were sacrificed,and the pathological changes of myocardial tissue were observed by HE staining.The levels of serum myocardial enzymescreatine kinase(CK),creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),troponin I(cTnI)],oxidation and antioxidant indicatorsmalondialdehyde(MDA),superoxide dismutase(SOD)and reactive oxygen species(ROS)]in blood and myocardial tissue and the expression of Nrf2,HO-1 protein and mRNA in myocardial tissue were detected.Results The myocardial fibers of the rats in the sham operation group were arranged neatly,but they were obviously broken in the model group.Compared with the model group,the pathological changes were significantly improved in each treatment group.The levels of serum CK,CK-MB,LDH,cTnI in the model group and the levels of MDA and ROS in blood and myocardial tissue were significantly higher than those in the sham operation group(all P<0.05),and the levels of the above indicators in each treatment group were significantly lower than those in the model group(P<0.05);the SOD levels in blood and myocardial tissue of the model group were significantly lower than those in the sham operation group(P<0.05),and the above-mentioned index levels in each treatment group were significantly higher than those in the model group(P<0.05).The expression levels of Nrf2 and HO-1 protein and mRNA in the myocardial tissue of the model group were significantly higher than those in the sham operation group(all P<0.05),and the expression levels of the above indicators in each treatment group were significantly higher than those in the model group(all P<0.05).Conclusion Chrysin may inhibit myocardial injury caused by ischemia-reperfusion by regulating the Nrf2/HO-1 signaling pathway and improving myocardial antioxidant capacity.