摘要
目的:探讨心肌重构过程中心肌中电导钙激活钾离子通道(KCa3.1)蛋白表达与氧化应激反应之间的关系。方法:雄性血管紧张素-肾素(AGT-REN)双转基因高血压(d TH)小鼠2、4、8、12月龄各6只进行相应指标检测。另取12只6月龄雄性d TH小鼠,随机分为2组:模型组(d TH组)和N-乙酰半胱氨酸(NAC)组。同时取6只d TH同品系野生C57B6小鼠作为对照(WT组)。NAC组小鼠腹腔注射NAC 400 mg·kg^(-1)·d^(-1),WT和d TH组小鼠腹腔注射等量生理盐水。4周后检测各组小鼠血压变化;ELISA法测定小鼠血浆中AngⅡ和Ang(1-7)含量变化;试剂盒检测心肌组织超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量;Western blot法检测小鼠心肌胶原蛋白collagen Ⅰ、collagen Ⅲ及K_(Ca)3.1蛋白表达的变化。结果:d TH组小鼠血压、血浆AngⅡ、MDA及胶原蛋白含量均高于同龄WT组小鼠(2月龄除外),并随年龄增长而增高(P<0.05);血浆Ang(1-7)和心肌SOD活性随年龄增长下降,并低于同龄WT组小鼠(2月龄除外)(P<0.05)。NAC干预使6月龄d TH小鼠心肌SOD活性增强(P<0.01),同时心肌MDA、胶原蛋白和K_(Ca)3.1蛋白表达下降(P<0.05)。结论:高血压所致心肌重构过程中心肌K_(Ca)3.1蛋白表达增加可能与心肌氧化应激水平增强有关。
AIM： To study the relationship between oxidative stress reaction and K_（Ca）3.1 protein expression in the process of myocardial remodeling. METHODS： The male AGT-REN double transgenic hypertension（ d TH） mice（ 2,4,8 and 12 months old,each n = 6） were used to detect the changes of the corresponding indexes. The male d TH mice（ 6months old） were randomly divided into 2 groups： d TH group and N-acetylcysteine（ NAC） group,and 6 wild-type（ WT）C57B6 mice served as controls. The mice in NAC group were treated with NAC at dose of 400 mg·kg^（- 1）·d^（- 1）,and the WT and model mice were treated with normal saline. After 4 weeks,the concentrations of Ang Ⅱ and Ang（ 1-7） in the plasma were measured by ELISA. The superoxide dismutase（ SOD） activity and malondialdehyde（ MDA） content were detected using SOD and MDA kits. The protein levels of collagen Ⅰ,collagen Ⅲ and K_（Ca）3.1were determined by Western blot. RESULTS： Compared with the WT mice,mean arterial blood pressure（ MAP）,concentration of Ang Ⅱ in the plasma,the content of MDA,and the protein expression of collagens and K_（Ca）3.1 in the myocardium of 4-,8-and 12-month-old d TH mice were increased,and gradually raised along with the age from 2 to 12 months（ P〈0. 05）,but the SOD activity in myocardium and Ang（ 1-7） content in plasma were decreased（ P〈0. 01）. NAC reduced the MAP,the content of MDA,and the protein expression of collagens and K_（Ca）3.1 in the myocardium of 6-month-old d TH mice（ P〈0. 05 or P〈0. 01）,and increased SOD activity compared with d TH group（ P〈0. 01）. CONCLUSION： Increased protein expression of myocardial K_（Ca）3.1 during myocardial remodeling induced by hypertension may be associated with enhancement of myocardial oxidative stress level.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2016年第5期869-873,共5页
Chinese Journal of Pathophysiology
基金
河北省自然科学基金资助项目(No.H2015209153)
华北理工大学大学生创新创业训练计划(No.X2015145)
