NADPH氧化酶-4对大鼠高血压性心肌肥大的影响

Effect of NADPH oxidase-4 on hypertension induced myocardial hypertrophy in rat

目的:研究NADPH氧化酶-4(NOX4)及活性氧(ROS)在高血压性心肌肥大发生过程中的作用.方法:采用手术缩窄大鼠腹主动脉致压力超负荷心肌肥厚的方法,制作大鼠高血压性心肌肥大模型.48只大鼠分为4组,即假手术组(或对照组)、心肌肥大模型组(模型组)、4羟基2,2,6,6四甲基哌啶(4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl,Tempol)治疗组(Tempol组)和二亚苯基碘(DPI)治疗组(DPI组).两治疗组分别于缩窄手术后给予含Tempol和DPI的饮用水.对4组大鼠,术前及术后2,4,8wk分别测定血压,术后8wk测定心脏质量指数以判断心肌肥大程度,术后8wk检测心肌组织中过氧化氢(H2O2)含量和NOX4mRNA表达.结果:模型组大鼠血压从术后2wk开始持续增高(P<0.01).两治疗组大鼠血压术后2wk时与模型组大鼠血压相同,但从术后4wk开始,Tempol和DPI的作用导致治疗组血压明显低于模型组(P<0.05).模型组左心室、心脏指数、心肌组织中H2O2含量及NOX4mRNA含量均显著高于对照组(P<0.01).DPI组以上指标则明显低于模型组(P<0.05);而Tempol组的左心室、心脏指数、H2O2含量明显低于模型组(P<0.05),但NOX4mRNA含量与模型组无明显差异.结论:心肌NOX4与大鼠高血压性心肌肥大的发展密切关联,其作用是通过它下游的活性氧而介导的.

AIM：To investigate the mRNA expression of NADPH oxidase-4（NOX-4） and its effect on hypertension induced cardiac hypertrophy in rat.METHODS：Model of over-loading myocardial hypertrophy was established through coarctation of abdominal aorta.Fourty-eight rats were randomly divided into 4 groups：Control group,model group,4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl（Tempol）-treatment group and Diphenylene iodonium（DPI）-treatment group.Tempol and DPI were administrated in the drinking water after the operation for the rats of the two treatment groups.Systolic blood pressure（SBP） was measured before the operation as well as 2,4 and 8 weeks after the operation.Further,at 8 weeks after the operation,heart weight indexes（LVW/BW and HW/BW） were measured to determined the level of cardiac hypertrophy.Hydrogen peroxide（H2O2） level was measured and the NOX4 mRNA was detected for all rats at 8 weeks after the operation.RESULTS：SBP of the model group increased 2 weeks after the operation and was higher than SBP of the control group at all time points after the operation（P0.01）.SBP＇s of both Tempol-and DPI-treatment groups were the same as that of the model group at 2 weeks after the operation,but became lower than SBP of the model group at 4 and 8 weeks after the operation（P0.05）.For the model group,the LVW/BW,HW/BW,H2O2 and NOX4 mRNA levels are higher than those of the control group at all time points after the operation（P0.01）.For the DPI-treatment group,the above parameters were all lower than those of the model group（P0.05）.For the Tempol-treatment group,the LVW/BW,HW/BW and H2O2 level were markedly lower than those of the model group（P0.05）,whereas the NOX4 mRNA level was the same as that of the model group.CONCLUSION：Hypertension induced cardiac hypertrophy is partly medicated by NOX4 and its downstream ROS.