瑞舒伐他汀抑制去氧皮质酮诱导大鼠心肌纤维化的作用影响

Rosuvastatin attenuates myocardial fibrosis in the heart of DOCA/salt rats

目的通过研究瑞舒伐他汀(ROS)对去氧皮质酮(DOCA)-盐联合诱导的大鼠心肌纤维化的干预效应,探讨ROS抑制盐皮质激素致心肌纤维化过程的可能机制。方法 60只雄性SD大鼠行右肾切除术,术后给予1%NaCl、0.2%KCl饮水4周并随机分为3组:对照组(CON组)、DOCA组、DOCA+ROS组。苦味酸天狼猩红染色观察大鼠心肌间质胶原容积分数(CVF);苏木精染色观察心肌间质炎症反应程度;免疫组化法观察心肌组织单核巨噬细胞抗原(ED-1)表达;免疫印迹法检测纤维连接蛋白表达。结果①第28天DOCA组出现明显纤维化,其CVF指标显著高于DOCA+ROS组(P<0.05),DOCA+ROS组与CON组的CVF无明显差异;②与CON组比较,DOCA组及DOCA+ROS组心肌间质可见明显炎症渗出及单核巨噬细胞浸润;③CON组和DOCA+ROS组纤维连接蛋白表达无明显差异,但均明显低于DOCA组(P<0.05)。结论盐皮质激素致心肌纤维化与心肌组织的炎症反应有关,ROS具备抑制DOCA-盐诱导的大鼠心肌纤维化作用,其机制可能与其抑制了盐皮质激素致心肌组织的炎症反应过程及减少心肌纤维化指标的表达有关。

Objective To investigate whether rosuvastatin would suppress myocardial fibrosis in deoxycorticosterone-acetate （DOCA）/salt hypertensive rats. Methods Sixty male unineph-rectomized SD rats were treated with 1% NaCl and 0. 2% KCl in the drinking water for 4 weeks and assigned to three groups： vehicle control rats（ CON group）, deoxycorticosteroae treated group （DOCA group）, deoxycorticosterone and rosuvastatin treated group （DOCA ＋ ROS group）. Collagen volume fraction （CVF） was analyzed by Sirius-Red staining. Myocardial tissue inflammation was analyzed by Hematoxylineosin staining. Ectodermal dysplasia-1 （ED-1） was analyzed by immunohistoehemistry. Expression of fibronectin was detected by Western blot. Results （1） The DOCA group showed severe myocardial fibrosis on the 28th day, and the CVF index were higher than DOCA ＋ ROS group apparently（ P 〈 0.05 ）. No significant difference of CVF between the DOCA ＋ ROS group and CON group was found （P 〉 0.05 ）. （2） Compared with the CON group, different degrees of myocardial tissue inflammation and monoeyte/maerophage infiltration were observed in the DOCA group and I）OCA ＋ ROS group. （3） Expressions of Fibronectin had no significant difference between the CON group and DOCA ＋ ROS （ P 〉 0. 05 ） , but was lower than DOCA Group （ P 〈 0.05 ）. Conclusion Mineralocortieoid-induced myocardial fibrosis is related to cardiac tissue inflammatory respons-e, rosuvastatin showed an inhibitory effect on myocardial fibrosis in the heart of DOCA/salt rats, the mechanism may be associated with the inhibition of the inflammatory response and fibrosis indices expressions in the heart of DOCA/salt rats.