Ang Ⅱ诱导大鼠心房肌纤维化的mRNA表达谱变化 Translated title: mRNA Expression Profile Changes in Angiotensin-Ⅱ-Induced Atrial Myocardial Fibrosis in Rats

Abstract

目的

研究血管紧张素Ⅱ（Ang Ⅱ）诱导的大鼠纤维化心肌细胞与正常大鼠心肌细胞mRNA表达谱之间的差异及其相关信号通路。

方法

8周龄雄性SD大鼠6只，随机分为对照组（Control组）和Ang Ⅱ组，每组3只。Control组每日经尾静脉注射生理盐水，Ang Ⅱ组则注射2 mg/kg的Ang Ⅱ，两组持续给药14 d。采用Masson染色法检测大鼠心肌纤维化程度，免疫组化法检测胶原蛋白Ⅰ含量。利用高通量测序技术检测两组大鼠心肌细胞mRNA的表达并筛选出差异mRNA，进行GO分析和KEGG通路分析。

结果

与Control组相比，Ang Ⅱ组的心肌纤维化程度及胶原蛋白Ⅰ含量升高（ P<0.05）。进行测序后共筛选出313条差异mRNA（其中201条上调，112条下调）。GO和KEGG分析表明上述差异表达的mRNA参与了心肌纤维化的多种生物学调节功能和通路。

结论

Ang Ⅱ可以导致大鼠心肌发生纤维化；纤维化的心肌细胞与正常心肌细胞之间的mRNA表达具有明显差异，差异表达的mRNA在免疫反应、细胞重构、细胞外基质沉积等生物过程中可能发挥重要作用。

Translated abstract

Objective

To study the differences between the mRNA expression profile in angiotensin Ⅱ (Ang Ⅱ)-induced fibrotic cardiomyocytes and that of normal cardiomyocytes and the relevant signaling pathways.

Methods

Six 8-week-old male Sprague-Dawley (SD) rats were randomly assigned to a control group and an Ang Ⅱ group, with 3 rats in each group. Rats in the control group were injected via caudal vein with 0.9% normal saline at 2 mg/kg per day, while rats in the Ang Ⅱ group were injected with Ang Ⅱ via caudal vein at 2 mg/kg per day. The medications were continuously administered in the two groups for 14 days. The degree of myocardial fibrosis was determined by Masson's Trichrome staining and the content of collagen Ⅰ was determined by immunohistochemistry. High throughput sequencing was performed to measure the mRNA expression of rat cardiomyocytes in the two groups and to screen for differentially-expressed mRNAs. The differentially-expressed mRNAs were analyzed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.

Results

Compared with those of the control group, the degree of myocardial fibrosis and the content of collagen Ⅰ in Ang Ⅱ group were significantly higher ( P<0.05). Through sequencing, 313 differentially-expressed mRNAs were identified, with 201 being up-regulated and 112 being down-regulated. Go and KEGG analyses showed that these differentially-expressed mRNA were involved in a variety of biological regulatory functions and pathways of myocardial fibrosis.

Conclusion

Ang Ⅱ can cause myocardial fibrosis in rats. There are significant differences in mRNA expression between fibrotic cardiomyocytes and normal cardiomyocytes. The differentially expressed mRNAs may play an important role in biological processes, including immune response, cell remodeling, and extracellular matrix deposition.