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LncRNA ROR facilitates myocardial fibrosis in rats with viral myocarditis through regulating C-Myc expression

机译:LncRNA ROR通过调节C-Myc表达促进病毒性心肌炎大鼠心肌纤维化

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OBJECTIVE: The aim of this study was to explore the effect of long non-coding ribonucleic acid (lncRNA) ROR on myocardial fibrosis in rats with viral myocarditis by regulating c-myc expression. MATERIALS AND METHODS: A total of 120 healthy male rats were randomly divided into three groups, including: blank control group (group N, healthy rats, n=40), model control group (group M, viral myocarditis, n=40), and group P (lncRNA ROR + viral myocarditis, n=40). At 5, 10, and 15 d after modeling, the rats were sacrificed. Meanwhile, the left ventricular mass index (LVMI), the left ventricular weight/tibial length (LVW/TL) and the heart mass index (HMI) were measured, respectively. The myocardial tissues of rats were observed via staining. The protein and mRNA expressions of the transforming growth factor-β (TGF-β) and c-myc in myocardial tissues were detected via Western blotting and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), respectively. Moreover, the level of the serum interleukin-6 (IL-6) was detected via enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with group N, HMI, LVMI, and LVW/TL in group M significantly increased at each time point (p0.01). Meanwhile, they were remarkably elevated at each time point in group P when compared with those in group M (p0.01). According to the results of hematoxylin-eosin staining (HE) staining, the myocardial fibers were normal and orderly arranged in group N. Meanwhile, no inflammatory cells were observed in group N. In group M, the proliferation of a large number of inflammatory cells was observed, and the myocardial cells were disorderly arranged and became enlarged. In group P, the myocardial fibrosis was significantly severer than that of the other two groups (p0.05). The results of the Masson staining revealed that there was significantly less accumulation of collagen fibers in myocardium in group N. There was a little accumulation of collagen fibers in the myocardium and fibrosis declined in group M. The myocardial fibrosis in group P remarkably increased when compared with group M (p0.05). According to the results of the Western blotting, the protein expressions of c-myc and TGF-β were significantly up-regulated in group P, compared with those in group M and N (p0.05). However, they were remarkably higher in group M than in group N (p0.05). QRT-PCR showed that the relative messenger ribonucleic acid (mRNA) expressions of c-myc and TGF-β were remarkably up-regulated in group P when compared with those in group M and N, showing statistically significant differences (p0.05). Moreover, they were significantly higher in group M than those in group N (p0.05). Besides, the expression level of serum IL-6 remained highest in group P (p0.01). CONCLUSIONS: LncRNA ROR up-regulates the expression of c-myc and increases the level of serum IL-6, thereby facilitating the proliferation and differentiation of cardiac fibroblasts.
机译:目的:本研究旨在通过调节c-myc的表达来探讨长非编码核糖核酸(IncRNA)ROR对病毒性心肌炎大鼠心肌纤维化的影响。材料与方法:将120只健康雄性大鼠随机分为三组,分别为:空白对照组(N组,健康大​​鼠,n = 40),模型对照组(M组,病毒性心肌炎,n = 40), P组(lncRNA ROR +病毒性心肌炎,n = 40)。建模后第5、10和15天,处死大鼠。同时,分别测量左心室质量指数(LVMI),左心室重量/胫骨长度(LVW / TL)和心脏质量指数(HMI)。通过染色观察大鼠的心肌组织。分别通过蛋白质印迹和定量实时聚合酶链反应(qRT-PCR)检测心肌组织中转化生长因子-β(TGF-β)和c-myc的蛋白质和mRNA表达。此外,通过酶联免疫吸附测定(ELISA)检测血清白细胞介素6(IL-6)的水平。结果:与N组相比,M组在每个时间点的HMI,LVMI和LVW / TL均显着升高(p <0.01)。同时,与M组相比,P组在每个时间点它们均显着升高(p <0.01)。根据苏木精-伊红染色结果,N组心肌纤维正常,有序排列。N组未见炎性细胞。M组大量炎性细胞增殖观察到心肌细胞无序排列并变大。在P组中,心肌纤维化明显比其他两组严重(p <0.05)。 Masson染色结果显示,N组心肌胶原纤维的积聚明显较少。M组心肌胶原纤维的积聚较少,而纤维化下降。P组心肌纤维化明显高于对照组。 M组(p <0.05)。根据Western blotting的结果,与M和N组相比,P组c-myc和TGF-β的蛋白表达明显上调(p <0.05)。但是,它们在M组中显着高于N组(p <0.05)。 QRT-PCR显示,与M和N组相比,P组c-myc和TGF-β的相对信使核糖核酸(mRNA)表达显着上调,差异有统计学意义(p <0.05)。此外,它们在M组中显着高于N组(p <0.05)。此外,P组血清IL-6的表达水平最高(p <0.01)。结论:LncRNA ROR上调c-myc的表达并增加血清IL-6的水平,从而促进心脏成纤维细胞的增殖和分化。

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