辛伐他汀对一氧化氮缺乏性高血压大鼠心肌纤维化的作用1

目的: 观察辛伐他汀对一氧化氮( NO) 缺乏性高血压大鼠心肌纤维化的作用。方法: 24 只WKY 大鼠随机分为正常对照组( C 组) 、硝基精氨酸甲酯( LNAME)组( L 组) 和L-NAME +辛伐他汀组( L +S组), 8 wk 后测定大鼠血清和心肌组织血管紧张素Ⅱ( Ang Ⅱ) 、血管紧张素转换酶(ACE) 活性和心肌组织羟脯氨酸浓度, 并取大鼠左心室心肌横截面组织作病理形态检测和计算机图象分析。结果: L 组大鼠血浆ACE 活性与C 组相比明显降低( P <0. 01), 心肌ACE 活性则较C 组明显增高( P <0. 01), 辛伐他汀干预后血浆ACE 活性升高, 但与L 组无显著差异( P >0. 05), 心肌ACE 活性则比L 组有明显降低( P <0. 05); 各实验组大鼠血浆Ang Ⅱ水平与C 组比较未显示统计学差异( P >0. 05); L 组心肌组织AngⅡ水平与C 组比较显著增加( P <0. 01), L +S 组心肌组织Ang Ⅱ水平则较L 组明显降低( P <0. 05); 此外, L 组心肌羟脯氨酸浓度和左心室胶原容积分数(CVF) 和心肌内血管周围胶原面积( PVCA) 均比C组明显增高( P <0. 01), L +S 组羟脯氨酸浓度和CVF 、PVCA 值则均较L 组明显降低( P <0. 05) 。结论: 辛伐他汀可能通过降低局部心肌组织ACE 活性减少Ang Ⅱ生成, 减轻心肌纤维化。

Effects of simvastatin on myocardial fibrosis in NO-deficient hypertensive rats

AIM: To investigate the effects of simvastatin on myocardial fibrosis in NO-deficient hypertensive rats. METHODS: Twenty-four male Wistar-Kyoto rats were divided into three groups: Control ( C) group, L-NAME ( L) group, and L-NAME plus Simvastatin ( L +S) group. The levels of ACE and Ang Ⅱ in plasma and myocardial tissue, and the contents of hydroxyproline concentration in myocardial tissue were measured after 8 weeks. The values of CVF, PVCA and the hydroproline concentration ( HC ) were studied using the methods of pathological examination combined with computed processing. RESULTS: The activity of ACE in serum in L group was lower than that in C group ( P <0. 01). Simvastatin treatment did not significantly increase the activity of ACE compared with L group ( P >0. 05). However, the activity of ACE in myocardial tissue was lower than that of C group ( P <0. 05). Although the levels of Ang Ⅱ in plasma were not altered by L-NAME ( P >0. 05), the concentrations of Ang Ⅱ in myocardial tissue ( P < 0. 01) were significantly increased in L group compared to C group. Simvastatin significantly decreased the levels of Ang Ⅱ in myocardial tissue ( P <0. 05). The hydroxyproline concentration and the value of PVCA and CVF in L group were significantly higher than that in C group ( P <0. 01), which were significantly attenuated by simvastatin tratment ( P <0. 05). CONCLUSION: Simvastatin may decrease the production of Ang Ⅱ and attenuate myocardial fibrosis via reducing the activity of ACE in NOdeficient hypertensive rats.