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. 2023 Jan 17:2023:7438567.
doi: 10.1155/2023/7438567. eCollection 2023.

Analysis of Function Role and Long Noncoding RNA Expression in Chronic Heart Failure Rats Treated with Hui Yang Jiu Ji Decoction

Huan Zhang  1 , Li Zhang  1 , Kejing Yin  1 , Miao Zhang  1 , Yanjiao Hao  1 , Hongwei Zhou  1 , Huifeng Ren  1
Affiliations

Analysis of Function Role and Long Noncoding RNA Expression in Chronic Heart Failure Rats Treated with Hui Yang Jiu Ji Decoction

Huan Zhang et al. J Healthc Eng. .

Abstract

Hui Yang Jiu Ji (HYJJ) decoction has been applied as a prescription of traditional Chinese medicine for the treatment of chronic heart failure (CHF). However, its comprehensive molecular mechanism remains unclear now. Our study aimed to explore the possible function and lncRNA-miRNA regulation networks of HYJJ on CHF induced by doxorubicin (DOX) in rats. Our study showed that HYJJ could recover cardiac function and alleviate myocardial injury of DOX-induced CHF. Besides, HYJJ had an effect on restraining myocardial apoptosis in CHF rats. Moreover, RNA-sequencing and bioinformatics analysis indicated that among a total of 548 significantly up- and down-regulated differentially expressed (DE) long noncoding RNA (lncRNA), 511 up- and down-regulated DE miRNAs were identified. Cushing's syndrome and Adrenergic signaling in cardiomyocytes were common pathways between DE-lncRNAs-enriched pathways and DE-miRNAs-enriched pathways. Finally, we observed a new pathway-MSTRG.598.1/Lilrb2 pathway with the HYJJ treatment; however, it needs further studies. In conclusion, this study provided evidence that HYJJ may be a suitable medicine for treating CHF. Moreover, several pivotal miRNAs may serve important roles in these processes by regulating some key miRNAs or pathways in CHF.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Hui Yang Jiu Ji decoction alleviated myocardial injury of CHF rats: (a) The diagram of modeling and grouping in this experiment. (b) Echocardiographic LVIDd and LVIDs values were detected in each group following CHF. (c) Percentages of EF and FS were calculated in each group after CHF. (d) HE staining of myocardial tissues in each group at a magnification of 200x and 400x. Scale bar = 10 μm. (e) Expression levels of cTNI and NT-proBNP in each group were determined by ELISA assay. Bars represented the mean ± S.D. from at least three independent experiments. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ∗∗∗∗p < 0.0001.
Figure 2
Figure 2
Hui Yang Jiu Ji decoction inhibited myocardial apoptosis of CHF rats: (a) The TUNEL-negative normal cells with blue nuclear fluorescence (DAPI) and TUNEL-positive cells with green nuclear fluorescence at a magnification of 400x. Scale bar = 20 μm. The results of the TUNEL assay were quantified by apoptosis rate in each group. (b) The WB band of c-caspase 3 was shown, and the relative expression level was normalized to β-actin. (c) The expression of c-caspase 3 was dyed green, and the cell nucleus was stained blue at a magnification of 100x. Scale bar = 100 μm. The level of c-caspase 3 was quantified by MFI. Bars represented the mean ± S.D. from at least three independent experiments. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ∗∗∗∗p < 0.0001.
Figure 3
Figure 3
Analysis of lncRNA DE genes in the mod vs. con and HY vs. mod comparisons: (a) Clustering heat map of total lncRNA genes in three groups. (b) Volcano plot of lncRNA DE expression analysis. (c) Clustering heat map of DE lncRNAs genes. (d) Venn diagram showing lncRNA DE genes. (e) Top 10 upregulated lncRNA DE genes and the top 10 downregulated lncRNA DE genes in HY vs. mod comparison. Con: control group, mod: CHF group, and HY: HYJJ group.
Figure 4
Figure 4
Gene ontology (GO) analysis of lncRNA DE genes: (a) GO enrichment analysis of lncRNA DE genes. (b) GO rich-factor analysis of lncRNA DE genes. Con: control group, mod: CHF group, and HY: HYJJ group.
Figure 5
Figure 5
Kyoto Encyclopaedia of genes and genomes (KEGG) analysis of lncRNA DE genes: (a) KEGG pathway enrichment analysis of lncRNA DE genes. (b) KEGG pathway rich-factor analysis of lncRNA DE genes. Con: control group, mod: CHF group, and HY: HYJJ group.
Figure 6
Figure 6
Analysis of miRNA DE genes in the mod vs. con and HY vs. mod comparisons: (a) Clustering heat map of total miRNA genes in three groups. (b) Volcano plot of miRNA DE expression analysis. (c) Clustering heat map of miRNAs DE genes. (d) Venn diagram showing common miRNA DE genes. (e) Top 20 upregulated miRNA DE genes and the top 20 downregulated miRNA DE genes (|log2 (fold change)| ≥ 2) in the HY vs. mod comparison. Con: control group, mod: CHF group, and HY: HYJJ group.
Figure 7
Figure 7
Gene ontology (GO) analysis of miRNA DE genes: (a) GO enrichment analysis of miRNA DE genes. (b) GO rich-factor analysis of miRNA DE genes. Con: control group, mod: CHF group, and HY: HYJJ group.
Figure 8
Figure 8
Kyoto Encyclopaedia of genes and genomes (KEGG) analysis of miRNA DE genes. (a) KEGG pathway enrichment analysis of miRNA DE genes. (b) KEGG pathway rich-factor analysis of miRNA DE genes. Con: control group, mod: CHF group, and HY: HYJJ group.
Figure 9
Figure 9
The potential interaction of miRNA and lncRNA. (a) The potential interaction of miRNA and lncRNA in the mod vs. con. Rectangles represent lncRNA, ellipses represent miRNA. Orange-red: upregulation, dark-blue: downregulation. (b) The potential interaction of miRNA and lncRNA in the HY vs. mod. Rectangles represent lncRNA, ellipses represent miRNA. Dark pink: upregulation, dark pink: downregulation. Con: control group, mod: CHF group, and HY: HYJJ group.
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