N-乙酰半胱氨酸对大鼠压力负荷型心肌肥厚的作用  

Effects of N-acetylcysteine on pressure-overload cardiac hypertrophy of rats

作　　者：屈扬扬[1] 杨霞[2] 刘奔[1] 刘艳丽[1] 李锐[1] 柴慧娟[1] 张玲[1] 

机构地区：[1]天津医科大学基础医学院生理教研室 [2]天津市胸科医院病理科,天津300051

出　　处：《中华高血压杂志》2013年第4期371-376,共6页Chinese Journal of Hypertension

基　　金：天津医科大学科学研究基金(NO.2011KY33)

摘　　要：目的探讨抗氧化剂N-乙酰半胱氨酸(NAC)对大鼠慢性压力负荷型心肌肥厚的影响及其相关机制。方法 7～8周龄雄性SD大鼠30只随机分成5组:假手术组、模型组、NAC100mg/(kg·d)组、NAC300mg/(kg·d)组、假手术+NAC300mg/(kg·d)组,每组6只,采用腹主动脉缩窄术制作压力负荷型心肌肥厚模型。于手术3d后NAC灌胃:100mg/(kg·d)组、NAC300mg/(kg·d)组及假手术+NAC300mg/(kg·d)组;假手术组和模型组给予相应体积蒸馏水。用药8周后,无创动脉血压仪检测鼠尾动脉血压,并行心脏超声检测,HE染色检测心肌肥厚情况并比较各组动物心肌细胞横截面积,荧光测定法检测线粒体反应性氧族(ROS)水平,Western blot检测心肌NADPH氧化酶4(NOX4)以及有活性的钙/钙调蛋白依赖性蛋白激酶CaMKⅡ(p-CaMKⅡ/CaMKⅡ)表达的变化。结果心脏超声检测发现模型组大鼠出现明显心肌肥厚,模型组大鼠与假手术组相比,心肌细胞横截面积增加[(10741.24±486.23)比(5490.55±244.96)μm2,P<0.05],线粒体ROS水平升高[(0.77±0.10)比(0.34±0.08)U/(s·m),P<0.05],心肌组织NOX4和p-CaMKⅡ的表达增加(均P<0.05);NAC明显逆转了腹主动脉缩窄引起的心肌肥厚,减小心肌细胞横截面积[NAC100mg/(kg·d)组(8088.16±103.68)μm2、NAC300mg/(kg·d)组(7297.96±213.92)μm2比模型组(10741.24±486.23)μm2,均P<0.05],降低了线粒体ROS生成速率[NAC100mg/(kg·d)组(0.46±0.06)U/(s·m)、NAC300mg/(kg·d)组(0.47±0.04)U/(s·m)比模型组(0.77±0.10)U/(s·m),均P<0.05],有效抑制了压力负荷诱导的NOX4及p-CaMKⅡ表达上调(P<0.05)。结论氧化应激与CaMKⅡ信号系统共同参与了压力负荷型心肌肥厚过程,NAC通过抗氧化作用,抑制CaMKⅡ表达上调而达到改善心肌肥厚的效应。Objective To investigate the effects of antioxidant N-acetylcysteine （NAC） on the pressure-overload car- diac hypertrophy in rats and its related mechanisms. Methods Thirty 7-8-week-old male SD rats were randomly divided into five groups（all n=6） ： sham operation group, model group, NAC 100 mg/（kg · d）group, NAC 300 mg/（kg · d） group, and sham operation^NAC 300 mg/（kg ~ d） group. A rat model of cardiac hypertrophy was established using abdominal aortic constriction. Three days after surgery, the NAC 100 mg/（kg ~ d）, the NAC 300 mg/（kg ~ d） group, and the sham operation＋NAC 300 rag/（ kg · d） group respectively received a intragastric administration of 100 mg/（kg · d）, 300 mg/（kg · d） and 300 mg/（kg · d）, while the sham operation group and the model group received an intragastric administration of distilled water for eight weeks. The systolic blood pressure （SBP） was measured by tail-cuff method and echoeardiography was performed. HE staining and myoeyte cross-sectional area （CSA） were used for the detection of myocardial hypertrophy. Myocardial mitocondrial reactive oxygen species （ROS） levels were measured by DCF fluorometry. The expressions of activated-CaMK II （p-CaMK II/CaMK II ） and NOX4 were determined by Western blot analysis. Results The results showed that model group rats developed an obvious cardiac hypertrophy examined by echocardiography. Compared with those of the sham operation group, myocyte CSA I-（10 741.24± 486.23） vs （5490.55±244.96）μm2 , P〈0.05] and eardiac mitochondrial ROS production [（0.774±0.10） vs （0.34±0.08）U/（s· m）, P 〈 0. 05 ] were significantly increased in the model group. The expressions of NOX4 and p-CaMK lI in model group rats were respectively increased （P〈0.05）. NAC significantly reversed the cardiac hypertrophy induced by abdominal aortic constriction, decreased myocyte CSA [NAC 100 mg/（kg · d） group： （8088.16±103.68）μm2 , NAC 300 mg/（kg · d） group： （72

关 键 词：N-乙酰半胱氨酸 氧化应激 钙 钙调蛋白依赖性蛋白激酶 压力负荷型心肌肥厚 

分 类 号：R965[医药卫生—药理学]