Liu Yu, Huang He, Tang Yan-hong, Li Hai-tao, Wang Xi, Huang Cong-xin
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2009 Oct;37(10):883-6.
To investigate the effects of NADPH oxidase inhibition on cardiac function and myocardial calcium regulatory proteins mRNA expressions in rabbits with heart failure (HF).
HF was induced by experimental aortic insufficiency and abdominal aortic constriction, HF animals were treated with oral apocynin (15 mg/d), a NADPH oxidase inhibitor or equal dose placebo. Eight weeks later, cardiac function was measured by echocardiography. Myocardial NADPH oxidase activity was evaluated by NADPH dependent superoxide production examined using superoxide dismutase-inhibitable cytochrome c reduction. Sarcoplasmic reticulum Ca(2+)ATPase (SERCA2a), ryanodine receptor 2 (RyR2), phospholamban (PLB) and sodium-calcium exchanger (NCX) were determined by RT-PCR.
Rabbits with HF developed ventricular dilatation and cardiac dysfunction, as well as increase in myocardial NADPH oxidase activity, decreases in mRNA expression of SERCA2a, RyR2 and PLB, and increase in mRNA expression of NCX. Apocynin significantly reduced NADPH oxidase activity (P < 0.05), upregulated SERCA2a, RyR2 and PLB mRNA expressions (SERCA2a/GAPDH: 0.63 +/- 0.11 vs. 0.34 +/- 0.08, RyR2/GAPDH: 0.23 +/- 0.04 vs. 0.17 +/- 0.06, PLB/GAPDH:1.28 +/- 0.13 vs. 0.95 +/- 0.09, P < 0.05), downregulated NCX mRNA expression (NCX/GAPDH: 0.67 +/- 0.10 vs. 0.95 +/- 0.12, P < 0.05), and improved cardiac function [LVEF: (60.06 +/- 10.07)% vs. (38.87 +/- 3.31)%, LVFS: (30.12 +/- 6.56)% vs. (17.40 +/- 2.45)%, P < 0.05] in rabbits with HF.
NADPH oxidase inhibition improves cardiac function possibly by preventing abnormal alterations in myocardial calcium regulatory proteins in failing heart.
探讨抑制NADPH氧化酶对心力衰竭（HF）家兔心功能及心肌钙调节蛋白mRNA表达的影响。
通过实验性主动脉瓣关闭不全和腹主动脉缩窄诱导HF，HF动物口服NADPH氧化酶抑制剂阿朴吗啡（15 mg/d）或等剂量安慰剂进行治疗。8周后，采用超声心动图测量心功能。通过使用超氧化物歧化酶抑制的细胞色素c还原法检测依赖NADPH的超氧化物生成来评估心肌NADPH氧化酶活性。通过RT-PCR测定肌浆网Ca(2+)ATP酶（SERCA2a）、兰尼碱受体2（RyR2）、受磷蛋白（PLB）和钠钙交换体（NCX）。
HF家兔出现心室扩张和心功能障碍，同时心肌NADPH氧化酶活性增加，SERCA2a、RyR2和PLB的mRNA表达降低，NCX的mRNA表达增加。阿朴吗啡显著降低了NADPH氧化酶活性（P < 0.05），上调了SERCA2a、RyR2和PLB的mRNA表达（SERCA2a/GAPDH：0.63±0.11对0.34±0.08，RyR2/GAPDH：0.23±0.04对0.17±0.06，PLB/GAPDH：1.28±0.13对0.95±0.09，P < 0.05），下调了NCX的mRNA表达（NCX/GAPDH：0.67±0.10对0.95±0.12，P < 0.05），并改善了HF家兔的心功能[左室射血分数：(60.06±10.07)%对(38.87±3.31)%，左室短轴缩短率：(30.12±6.56)%对(17.40±2.45)%，P < 0.05]。
抑制NADPH氧化酶可能通过防止衰竭心脏中心肌钙调节蛋白的异常改变来改善心功能。
