【摘要】：阿托伐他汀在全球范圍內(nèi)廣泛的應(yīng)用,能強(qiáng)效降低低密度脂蛋白膽固醇(LDL-C),被證實(shí)能減少主要心血管病事件和安全性良好。但是對醛固酮誘導(dǎo)心肌纖維化的干預(yù)作用及機(jī)制尚不明確。本研究隨機(jī)選取雌性SD大鼠共40只,在實(shí)驗(yàn)的前期對其進(jìn)行右腎切除,術(shù)后1周用1%的氯化鈉喂飲,持續(xù)4周,并隨機(jī)均分為4組:CON組(對照組),ALD組(醛固酮組),ALD+SPI組(醛固酮+安體舒通組),ALD+ATO組(醛固酮+阿托伐他汀組)。頸動脈插管以測量SD大鼠的平均動脈壓(MABP);SD大鼠的心肌組織用HE染色法以觀察心肌的病變程度,F3BA膠原特異性染色觀察并測量大鼠的心肌間質(zhì)膠原分?jǐn)?shù)(CVF)與心肌血管周圍膠原面積比(PVCA);通過免疫組化染色觀察并檢測血小板衍生生長因子(PDGF-A,PDGF-B),血小板衍生生長因子受體(PDGFR-α,PDGFR-β)及單核巨噬細(xì)胞抗原(ED-1)的表達(dá)水平;免疫印跡法檢測骨橋蛋白(OPN)的表達(dá)水平。研究表明,ALD組、ALD+SPI組、ALD+ATO組的SD大鼠的MABP值均比CON組顯著要高(p0.01或p0.05);ALD組的CVF和PVCA表達(dá)水平明顯比其它各組要高(p0.01或p0.05),ALD+SPI組和ALD+ATO組的CVF和PVCA表達(dá)水平相比較,無統(tǒng)計學(xué)差異(p0.05);各組間PDGF-A、PDGF-B、PDGFR-α、ED-1和OPN的表達(dá)水平進(jìn)行比較,ALD組明顯高于其他各組(p0.01或p0.05),ALD+ATO組除ED-1表達(dá)水平明顯低于ALD+SPI組(p0.05)外,其余與ALD+SPI組無統(tǒng)計學(xué)差異(p0.05);各組間PDGF-B的表達(dá)水平均無統(tǒng)計學(xué)差異(p0.05)。我們的研究初步表明:在醛固酮誘導(dǎo)的大鼠心肌纖維化的發(fā)生、發(fā)展中,阿托伐他汀對其具有抑制作用,其作用機(jī)制可能與降低巨噬細(xì)胞的浸潤,抑制OPN的表達(dá),部分抑制PDGFs及其受體的表達(dá)水平相關(guān)。
[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- 偽, 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- 偽, 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.
【作者單位】： 河南應(yīng)用技術(shù)職業(yè)學(xué)院;
【基金】：河南省高等學(xué)校重點(diǎn)科研項(xiàng)目(No.17A360008)資助
【分類號】：R965

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