醛固酮对动脉损伤和高脂喂养大鼠颈动脉粥样硬化的影响及通心络对该影响的阻断作用

Role of aldosterone in artery injury plus high-cholesterol diet-induced atherosclerosis in rats and the protective effect of Tongxinluo

目的观察醛固酮对动脉损伤和高脂喂养大鼠颈动脉粥样硬化的影响及通心络对该影响的阻断作用。方法40只雄性SD大鼠予高脂饮食、左颈总动脉内膜损伤、维生素D_3注射,随机分成模型组、醛固酮组、伊普利酮组、通心络组和醛固酮+通心络组。术前取血,4个月后取血及左颈总动脉标本。观察斑块面积、巨噬细胞阳性计数、血清C-反应蛋白(CRP)和白细胞介素(IL)-6的浓度。结果醛固酮组的颈动脉斑块面积为(1.83±0.49)mm^2,较模型组的(0.89±0.22)mm^2增加近1倍(P<0.05),亦明显大于醛固酮+通心络组的(1.32±0.54)mm^2(P<0.05)。醛固酮组斑块内巨噬细胞数量为(14.9±2.7)个,明显多于模型组的(11.9±0.7)个(P<0.05);醛固酮+通心络组的巨噬细胞数量为(6.9±0.73)个,明显少于模型组和醛固酮组(P值均<o.05)。与模型组比较,醛固酮组血清CRP浓度明显升高(P<0.05),伊普利酮组和通心络组均明显降低(P值均<0.01);与醛固酮+通心络组比较,通心络组血清CRP浓度明显降低(P<0.05),醛固酮组明显升高(P<0.01)。与模型组比较,醛固酮组血清IL-6浓度明显升高(P<0.05),伊普利酮组明显降低(P<0.05),通心络组虽有所降低,但差异无统计学意义(P>0.05);与醛固酮组比较,醛固酮+通心络组血清IL-6浓度明显降低(P<0.05)。结论醛固酮可以增加动脉粥样硬化程度,其作用机制可能与促进炎症反应有关。通心络具有醛固酮拮抗作用,可能为其抗动脉粥样硬化作用的一个新机制。

Objective To study the role of aldosterone in carotid artery injury and high-cholesterol diet-induced atherosclerosis in rats and the protective effects of Tongxinluo, a traditional Chinese medicine. Methods Forty male SD rats were given endothelium denudation of left carotid artery, high-cholesterol diet and intramuscular Vitamin D3. The rats were then randomly divided into 5 groups： model group received no special treatment, aldosterone treatment group, eplerenone treatment group, Tongxinluo treatment and Tongxinluo＋aldosterone treatment group. Blood samples were obtained before operation and 4 months later and the left carotid artery specimens were harvested; the plaque area, macrophage number, serum C-reactive protein（CRP） and interleukin-6 （IL-6） concentrations were examined. Results The plaque area in the model group was（0. 89 ± 0. 22） mm^2 , significantly lower than that of aldosterone treatment group （[1. 83 ± 0.49] mm^2 , P 〈 0.05）and higher than that of Tongxinluo＋aldosterone treatment group（[1.32 ± 0. 543 mm^2）, P 〈 0.05）. The macrophage number in aldosterone group（14.9±2.7） was significantly higher than that of model group（11.85±0. 7, P〈 0.05）; the number in aldosterone＋ Tongacinluo group was significantly less than those in the model group and aldosterone group （both P 〈0.05）. The CRP level in the model group was markedly lower than that of the aldosterone group （P 〈 0.05）, and higher than those in the eplerenone group and Tongxinluo group （both P 〈 0.05） ; the CRP level in aldosterone＋ Tongxinluo group was significantly higher than that of Tongxinluo group and lower than that ofaldosterone group （both P 〈 0. 05）. The levei of IL-6 in the model group was lower than that of aldosterone group （P 〈 0. 05） and higher than those of eplerenone group （P 〈 0. 05）and Tongxinluo group; the level in aldosterone group was significantly higher than that of aldosterone＋Tongxinluo group （P 〈 0. 05）. Conclusion Aldosterone can exacerbate atherosclerosis in rats and the mechanism might be related to the promotion of inflammatory reaction. Tongxinluo can antagonize the effect of aldosterone, which might be one of the mechanisms for its anti-atherosclerosis effect. （Shanghai Med J, 2007, 30：730-733）