过表达Nrf2对慢性心力衰竭小鼠自主神经调节影响

Effect of overexpression of Nrf2 on autonomic nerve regulation in mice with chronic heart failure

目的 探讨过表达核因子E2相关因子2(Nrf2)对慢性心力衰竭小鼠自主神经调节的影响。方法60只SD小鼠分为对照组、心衰组、过表达Nrf2组,每组20只,应用异丙肾上腺素建立慢性心力衰竭小鼠模型,用pcDNA3.1-Nrf2重组质粒干预,比较各组一般情况、心肌病理变化、心脏自主神经变化[乙酰胆碱(ACH)、去甲肾上腺素(NE)、乙酰胆碱转移酶(ChAT)、酪氨酸羟化酶(TH)]、心功能[左室短轴缩短率(FS)、左室射血分数(EF)]、心肌组织中Nrf2表达量。结果 过表达Nrf2组的心肌病理改变较心衰组明显减轻。过表达Nrf2组和心衰组NE含量[分别为(505.47±56.57)pg/mL、(1188.17±80.63)pg/mL]、TH含量[分别为(232.71±32.26)pg/mL、(490.02±70.56)pg/mL]高于对照组[分别为(359.56±43.10)pg/mL、(490.02±70.56)pg/mL](P<0.05);过表达Nrf2组NE、TH含量低于心衰组(P<0.05);过表达Nrf2组和心衰组ACH、CHAT含量及EF、FS低于对照组(P<0.05);过表达Nrf2组ACH、CHAT含量及EF、FS高于心衰组(P<0.05);心衰组Nrf2表达量低于对照组(P<0.05);过表达Nrf2组Nrf2表达量高于心衰组和对照组(P<0.05)。结论 过表达Nrf2在调节心脏自主神经和心功能方面具有一定改善作用。

Objective To investigate the effect of overexpression of nuclear factor-erythroid related factor-2(Nrf2on autonomic nerve regulation in mice with chronic heart failure. Methods Sixty SD mice were divided into control group,heart failure group and overexpression Nrf2 group,with 20 mice in each group. Mice were made into chronic heart failure models by isoproterenol and were intervened with pcDNA3.1-Nrf2 recombinant plasmid. The general condition,myocardial pathological changes,cardiac autonomic nerve changes[acetylcholine(ACH),norepinephrine(NE),choline acetyl transferase(ChAT),tyrosine hydroxylase(TH)],cardiac function[left ventricular fractional shortening(FS),left ventricular ejection fraction(EF)],and the expression of Nrf2 in myocardial tissue were compared. Results HE staining showed that the myocardial pathological changes in Nrf2 overexpression group were significantly milder compared with those of heart failure group. NE and TH contents among three groups were the highest in heart failure group,followed by Nrf2 overexpression group,and were the lowest in control group,with statistic difference(P<0.05). ACH and CHAT contents as well as EF and FS among three groups were the highest in control group,followed by Nrf2 overexpression group,and were the lowest in heart failure group,with statistic difference(P<0.05). The expression level of Nrf2 was the highest in Nrf2 overexpression group,followed by control group,and were the lowest in heart failure group,with significant difference(P<0.05). Conclusion Overexpression of Nrf2 has certain effect in regulating cardiac autonomic nerve and cardiac function.