阿托伐他汀对1型糖尿病心肌病大鼠心肌纤维化的作用及机制探讨  

Effect of atorvastatin on myocardial fibrosis of type Ⅰ diabetic cardiomyopathy in rats and its mechanism

作　　者：艾文[1] 谢培益[1] 陈延伟[1] 刘宗波[1] 陈菲[1] 苏又苏[1] 

机构地区：[1]广东医学院附属南山医院,广东深圳518052

出　　处：《山东医药》2013年第24期32-35,I0002,共5页Shandong Medical Journal

基　　金：广东省深圳市科技计划项目(201103317)

摘　　要：目的观察阿托伐他汀对1型糖尿病心肌病(DCM)大鼠心肌纤维化的作用,并探讨其可能的机制。方法将50只Wistar大鼠随机分为A、B组各15只和C、D组各10只,A、B组腹腔注射链尿佐菌素(STZ)70 mg/kg造模,C、D组腹腔注射等体积柠檬酸缓冲液。B、D组给予阿托伐他汀5 mg/kg灌胃1次/d,A、C组给予等体积生理盐水灌胃。监测大鼠体质量、空腹血糖,造模8周时超声检测心脏左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室后壁厚度(LVPWD)、短轴缩短率(FS)、射血分数(EF);取心脏组织,计算心脏重量与体质量的比值(HW/BW),Masson染色观察心肌组织纤维化,Western bolt法检测心肌组织中的表皮生长因子受体(EGFR)蛋白。结果造模2周后开始,A、B组体质量较C、D组显著降低(P均<0.05),空腹血糖明显升高(P均<0.01);造模8周时,与C、D组比较,A组LVESD、LVPWD、HW/BW增加(P均<0.05),EF值降低(P均<0.05),B组较A组LVESD、LVPWD、HW/BW、EF值变化程度小(P均<0.05);Masson染色可见A组心肌纤维细胞增生明显,B组较A组增生减少(P<0.05)。A、B组心肌组织EGFR蛋白表达水平高于C、D组(P均<0.05),B组表达水平低于A组(P<0.01)。结论阿托伐他汀能够减轻DCM大鼠心肌纤维化,该作用与其降低心肌组织中EGFR蛋白表达有关。Objective To observe the effect of atorvastatin on myocardial fibrosis of type I diabetic cardiomyopathy （DCM） in rats and to investigate the mechanism. Methods Fifty 8-week-old male Wistar rats were randomly divided into four groups： group A （n = 15） , group B （n = 15） , group C （n = 10） and group D （n = 10）. Group A and B were established by intraperitoneal injection of streptozotocin （ STZ）, group C and D were injected by equal volume citrate buffer solution. Group B and D were taken atorvastatin 5mg/kg orally and daily, group A and C were given an equal volume of saline. Body weight and fasting blood glucose of rats were monitored. After 8 weeks, left ventrieular end-diastolic dimension （LVEDD） , left ventrieular end systolic diameter （LVESD） , left ventricular posterior wall thickness（LVPWD） , left ventricular fractional shortening（FS） and ejection fraction（EF） were detected by echocardiography. The heart tissue was ob- tained to calculate the ratio of heart weight to body weight （HW/BW） and to observe the myocardial fibrosis by using Masson staining. EGFR protein of myocardial tissue was measured by Western blot. Results Two weeks after STZ injection, the body weight was significantly lower in group A and B than that in group C and D （ all P 〈 0.05 ）, fasting blood glucose in group A and B was increased more significantly than that in group C and D （ all P 〈0.01 ） ; eight weeks after STZ injection, compared with group C and D, the LVESD, LVPWD and HW/BW were significantly increased in group A （ all P 〈 0.05 ） , and the EF value was obviously decreased （ all P 〈 0.05 ） ; the degree of these changes was reduced in group B compared with group A （ all P 〈 0.05 ）. Masson staining showed that cardiac fibroblast proliferation in group A and B were significantly stronger than group C and D （ P 〈 0.05 ）, the expression level of EGFR protein in group A and B were markedly higher than group C and D （ all P 〈 0.05）, and those ch

关 键 词：糖尿病 心肌病 阿托伐他汀 表皮生长因子受体 纤维化 大鼠 

分 类 号：R542.2[医药卫生—心血管疾病] R332[医药卫生—内科学]