【摘要】 目的　探讨高胆固醇饮食诱导心肌纤维化及其可能的发生机制。方法　取 8周龄Wister大鼠 19只 ,随机分成正常对照组、高胆固醇组和螺内酯治疗组 ,以羟脯氨酸法测得左心室心肌胶原蛋白含量 ;以放免法分别测得左心室心肌组织血管紧张素Ⅱ(AngⅡ)和醛固酮 (Ald)含量及血浆AngⅡ、Ald浓度 ;以Griess法测得血清亚硝酸盐 (NO-2 )浓度 ;以核素标记法测得丝裂素活化蛋白激酶 (MAPK)活性。结果　高胆固醇饮食喂养 8周后 ,大鼠左心室心肌胶原蛋白、Ald含量及血浆AngⅡ浓度分别升高 1 2、1 1和 3 0倍 ;血清NO-2 浓度显著下降 ;用螺内酯治疗后 ,心肌胶原蛋白含量、血浆、组织AngⅡ水平和心肌MAPK活性下降(与高胆固醇组比较 ,P <0 0 5 )。结论　高胆固醇饮食诱导心肌纤维化 ,可能与循环和心肌醛固酮有关 ;MAPK可能是醛固酮介导心肌纤维化的重要的细胞外信号传递因子。更多还原

【Abstract】 Objective To study induction of myocardial fibrosis by high-cholesterol diet and its mechanism in rat. Methods Nineteen Wister rats aged 8 weeks were randomly divided into control group, high-cholesterol diet group and spironolactone treatment group. Collagen in left ventricular tissues was determined by oxyproline assay, contents of angiotensin Ⅱ(Ang Ⅱ) and aldosterone (Ald) and in left ventricular tissue their plasm concentration were determined by radioimmunoassay. Serum nitrite level was measured by Griess assay. Mitogen activated protein kinase (MAPK) was assessed by radioisotope labeled assay. Results The contents of collagen, cardiac Ald and plasma Ang Ⅱ in the myocardium of the left ventricle were increased 1.2, 1.1 and 3.0 fold, respectively, while serum level of nitrite (NO - 2) was significantly decreased in high-cholesterol diet group compared with control group. The contents of myocardial collagen and Ald, and plasma Ang Ⅱ and the activities of MAPK were decreased in high-cholesterol diet group treated with spironolactone for 8 weeks (P<0.05). Conclusion Myocardial fibrosis induced by high-cholesterol diet might be directly related to the circulatory and local tissue levels of aldosterone, and MAPK might be the important extracellular signal transducer in aldosterone mediated myocardial fibrosis.更多还原