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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(p<0.01或p<0.05);ALD组的CVF和PVCA表达水平明显比其它各组要高(p<0.01或p<0.05),ALD+SPI组和ALD+ATO组的CVF和PVCA表达水平相比较,无统计学差异(p>0.05);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(p<0.01或p<0.05),ALD+ATO组除ED-1表达水平明显低于ALD+SPI组(p<0.05)外,其余与ALD+SPI组无统计学差异(p>0.05);各组间PDGF-B的表达水平均无统计学差异(p<0.05)。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。
The widespread use of atorvastatin worldwide to reduce LDL-C strongly has been shown to reduce major cardiovascular events and safety. However, the intervention of aldosterone-induced myocardial fibrosis and its mechanism are not yet clear. In this study, a total of 40 female SD rats were randomly selected to undergo a right nephrectomy at the early stage of the experiment. After 1 week of operation, they were fed with 1% sodium chloride for 4 weeks and were randomly divided into 4 groups: CON (Control group), ALD group (aldosterone group), ALD + SPI group (aldosterone + spironolactone group), ALD + ATO group (aldosterone + atorvastatin group). Carotid arteries were cannulated to measure the mean arterial pressure (MABP) of SD rats. The myocardial tissues of SD rats were observed by HE staining to observe the myocardial lesions. The collagen content of myocardial interstitium was observed and measured by F3BA collagen staining (PDGF-A, PDGF-B) and platelet-derived growth factor receptor (PDGFR-α, PDGFR-β) were measured by immunohistochemical staining. ) And monocyte-macrophage antigens (ED-1). Western blotting was used to detect the expression of osteopontin (OPN). The results showed that MABP values of SD rats in ALD, ALD + SPI and ALD + ATO groups were significantly higher than those in CON group (p <0.01 or p <0.05). CVF and PVCA expression levels in ALD group were significantly higher than those in COND group There was no significant difference in the expression of CVF and PVCA between the ALD + SPI group and the ALD + ATO group (p> 0.05). The levels of PDGF-A, PDGF B, PDGFR-α, ED-1 and OPN in ALD group were significantly higher than those in other groups (p <0.01 or p <0.05) (P <0.05). There was no significant difference between other groups and ALD + SPI group (p> 0.05). There was no significant difference in the expression of PDGF-B among all groups (p <0.05). Our study initially showed that atorvastatin could inhibit aldosterone-induced myocardial fibrosis in rats and its mechanism may be related to the decrease of macrophage infiltration, the inhibition of the expression of OPN and the partial inhibition PDGFs and their receptors expression level.