熊果酸对高血压大鼠心肌纤维化及p38活化的影响

目的:观察熊果酸(UA)对高血压大鼠心肌纤维化的影响。方法:行腹主动脉结扎构建高血压大鼠心肌纤维化模型,实验大鼠分为假手术组、模型组、UA低、中、高剂量组[分别为10 mg/(kg·d)、20 mg/(kg·d)、40 mg/(kg·d)],每日灌胃给药1次。干预2个月后,测定血压、心脏重量指数(HMI)、左室重量指数(LVMI)、心功能指数、心肌细胞横径、Ⅰ型胶原蛋白表达和胶原体积分数。免疫印迹法测定p38磷酸化。免疫沉淀法测定p38活性。结果:UA能显著降低模型组心肌p38磷酸化及活性,下调血压、CHMI、LVMI、心肌细胞横径、Ⅰ型胶原蛋白表达和胶原体积分数,抑制心肌纤维化导致的心功能下降。结论:UA能抑制高血压大鼠心肌纤维化,抑制p38活化是其机制之一。

Effects of ursolic acid on cardiac fibrosis of hypertensive rats and p38 activation

Objective To observe effects of ursolic acid(UA) on hypertension-induced cardiac fibrosis. Methods After establishing the model of hypertension by ligation of abdominal aorta, animals were divided into sham-operation group, model group, low-dose UA group, middle-dose UA group and high-dose UA group. As indexes of cardiac fibrosis, collagen volume fraction, heart mass index, left ventricle mass index and Collagen I expression were measured. The phosphorylations of p38 were assessed using Western blot; the activity of p38 was assessed by immuno-precipitation. Results Ursolic acid decreased the indexes of cardiac fibrosis, inhibited the phosphorylations and activity of p38 MAPK. Conclusion Ursolic acid can lessen cardiac fibrosis of hypertensive rats and depression of p38 activation could be one of the mechanisms.