阿托伐他汀对醛固酮诱导大鼠心肌纤维化的干预作用及机制

发布时间：2018-11-23 11:59

【摘要】：阿托伐他汀在全球范围内广泛的应用,能强效降低低密度脂蛋白胆固醇(LDL-C),被证实能减少主要心血管病事件和安全性良好。但是对醛固酮诱导心肌纤维化的干预作用及机制尚不明确。本研究随机选取雌性SD大鼠共40只,在实验的前期对其进行右肾切除,术后1周用1%的氯化钠喂饮,持续4周,并随机均分为4组:CON组(对照组),ALD组(醛固酮组),ALD+SPI组(醛固酮+安体舒通组),ALD+ATO组(醛固酮+阿托伐他汀组)。颈动脉插管以测量SD大鼠的平均动脉压(MABP);SD大鼠的心肌组织用HE染色法以观察心肌的病变程度,F3BA胶原特异性染色观察并测量大鼠的心肌间质胶原分数(CVF)与心肌血管周围胶原面积比(PVCA);通过免疫组化染色观察并检测血小板衍生生长因子(PDGF-A,PDGF-B),血小板衍生生长因子受体(PDGFR-α,PDGFR-β)及单核巨噬细胞抗原(ED-1)的表达水平;免疫印迹法检测骨桥蛋白(OPN)的表达水平。研究表明,ALD组、ALD+SPI组、ALD+ATO组的SD大鼠的MABP值均比CON组显著要高(p0.01或p0.05);ALD组的CVF和PVCA表达水平明显比其它各组要高(p0.01或p0.05),ALD+SPI组和ALD+ATO组的CVF和PVCA表达水平相比较,无统计学差异(p0.05);各组间PDGF-A、PDGF-B、PDGFR-α、ED-1和OPN的表达水平进行比较,ALD组明显高于其他各组(p0.01或p0.05),ALD+ATO组除ED-1表达水平明显低于ALD+SPI组(p0.05)外,其余与ALD+SPI组无统计学差异(p0.05);各组间PDGF-B的表达水平均无统计学差异(p0.05)。我们的研究初步表明:在醛固酮诱导的大鼠心肌纤维化的发生、发展中,阿托伐他汀对其具有抑制作用,其作用机制可能与降低巨噬细胞的浸润,抑制OPN的表达,部分抑制PDGFs及其受体的表达水平相关。
[Abstract]:Atto vastatin is widely used around the world. It can effectively reduce low density lipoprotein cholesterol (LDL-C) and has been proven to reduce major cardiovascular events and safety. However, the effect and mechanism of aldosterone-induced myocardial fibrosis are unclear. In this study, 40 female SD rats were randomly divided into four groups: CON group (control group,), ALD group) and aldosterone group, which were fed with 1% sodium chloride for 4 weeks at the early stage of the experiment, and were randomly divided into four groups: the control group (), ALD group), the aldosterone group (control group), the control group (), ALD group), and the control group (aldosterone group). ALD SPI group (aldosterone acetonolactone group,), ALD ATO group (aldosterone Atto vastatin group). Carotid artery intubation to measure mean arterial pressure (MABP);) in SD rats Myocardial tissue of SD rats was stained with HE to observe the degree of myocardial lesion. F3BA collagen specific staining was used to observe and measure the ratio of myocardial interstitial collagen fraction (CVF) to myocardial perivascular collagen area (PVCA);) in rats. The expression of platelet-derived growth factor (PDGF-A,PDGF-B), platelet-derived growth factor receptor (PDGFR- 伪, PDGFR- 尾) and mononuclear macrophage antigen (ED-1) were detected by immunohistochemical staining. The expression of osteopontin (OPN) was detected by Western blot. The results showed that the MABP value of SD rats in, ALD SPI group of ALD group was significantly higher than that in CON group (p0.01 or p0.05). The expression of CVF and PVCA in ALD group was significantly higher than that in other groups (p0.01 or p0.05), ALD SPI group and ALD ATO group, there was no significant difference in CVF and PVCA expression level (p0.05). The expression levels of PDGF-A,PDGF-B,PDGFR- 伪, ED-1 and OPN in the ALD group were significantly higher than those in the other groups (p0.01 or p0.05), ALD ATO, except the ED-1 expression level was significantly lower than that in the ALD SPI group (p0.05). There was no significant difference between the rest and ALD SPI group (p0. 05). There was no significant difference in the expression of PDGF-B among the groups (p0. 05). Our results suggest that Atto vastatin inhibits the development of aldosterone induced myocardial fibrosis in rats, and its mechanism may be to reduce the infiltration of macrophages and inhibit the expression of OPN. Partial inhibition of the expression of PDGFs and its receptors was related.
【作者单位】：河南应用技术职业学院;
【基金】：河南省高等学校重点科研项目(No.17A360008)资助
【分类号】：R965

【相似文献】