OBJECTIVE: To investigate the mechanism of Qixuan Yijianing(芪玄抑甲宁,QYN) in minimizing cardiac injury in Graves′ disease(GD) mice using micro RNA(mi RNA) sequencing analysis. METHODS: Female BALB/c mice were rando...OBJECTIVE: To investigate the mechanism of Qixuan Yijianing(芪玄抑甲宁,QYN) in minimizing cardiac injury in Graves′ disease(GD) mice using micro RNA(mi RNA) sequencing analysis. METHODS: Female BALB/c mice were randomly divided into the modeling and control groups(CG). The modeling group was established with Ad-TSHR289. Following 10 weeks of successful modeling, the mice were randomly assigned to four groups: model(MG), methimazole(MMI), QYN low-dose(LD), and high-dose(HD). After four weeks of treatment, the heart rate, heart volume, and heart index were measured, and the levels of aspartate aminotransferase(AST), lactate dehydrogenase(LDH), α-hydroxybutyrate dehydrogenase( α-HBD), creatine kinase(CK), and creatine kinase MB isoenzyme(CK-MB) in the serum were detected using a biochemical analyzer. Hematoxylin-eosin and Masson staining were used to determine histological changes in cardiac tissue. The heart tissues in the CG, MG, and HD groups were selected, and mi RNA sequencing was used to identify differentially expressed mi RNAs. A bioinformatics database was used to predict the target genes of differential mi RNAs, and Gene Ontology(GO), and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were conducted on the predicted target genes. RESULTS: As compared to the CG group, the MG group's heart rate, heart volume, heart index, AST, CK, CK-MB, LDH, α-HBD, myocardial fiber thickness, and collagen fiber significantly increased, all P < 0.01, while following QYN, these indicators improved in the HD group, all P < 0.01 or P < 0.05. Compared to the CG group, the MG group identified 151 differentially expressed mi RNAs, with 42 mi RNAs downregulated and 109 mi RNAs upregulated;compared to the MG group, the HD group identified 70 differentially expressed mi RNAs, 40 were downregulated, and 30 were upregulated. The GO functions of differential mi RNA target genes are mostly enriched in cardiac development regulation, cardiac contraction control, heart rate regulation, and so on. The most enriched KEGG pathways include the mitogenactivated protein kinase, Erb B, Hippo, forkhead box protein O, and Wnt signaling pathways. CONCLUSION: QYN may protect the cardiac structure and function and minimize cardiac damage caused by GD by regulating relevant target genes and signaling pathways through mi RNAs which include mi R-206-3p, mi R-122-5p, and mi R-200a-3p.展开更多
基金Research Grant from the National Natural Science Foundation of China:Mechanism Study on the Treatment of Graves'Disease with Yiqi Yangyin Qinggan Sanjie Method based on T helper cell 17 and Related Factors (No. 81302898)Mudanjiang Medical University Research Initiation Fund Project Funding:Mechanism Study on the Treatment of Graves'Disease with Yiqi Yangyin Qinggan Sanjie Method Based on Thyroid Angiogenesis (No.2023-MYBSKY-008)Funding for the Mudanjiang City Applied Technology Research and Development Program Project:Metabolomics study of extract of Herb of Common Leibnitzia based on Ultra Performance Liquid Chromatography-Time of Flight Mass Spectrometry Technology on Collagen-induced Arthritis Rats (No. HT2020NS093)。
文摘OBJECTIVE: To investigate the mechanism of Qixuan Yijianing(芪玄抑甲宁,QYN) in minimizing cardiac injury in Graves′ disease(GD) mice using micro RNA(mi RNA) sequencing analysis. METHODS: Female BALB/c mice were randomly divided into the modeling and control groups(CG). The modeling group was established with Ad-TSHR289. Following 10 weeks of successful modeling, the mice were randomly assigned to four groups: model(MG), methimazole(MMI), QYN low-dose(LD), and high-dose(HD). After four weeks of treatment, the heart rate, heart volume, and heart index were measured, and the levels of aspartate aminotransferase(AST), lactate dehydrogenase(LDH), α-hydroxybutyrate dehydrogenase( α-HBD), creatine kinase(CK), and creatine kinase MB isoenzyme(CK-MB) in the serum were detected using a biochemical analyzer. Hematoxylin-eosin and Masson staining were used to determine histological changes in cardiac tissue. The heart tissues in the CG, MG, and HD groups were selected, and mi RNA sequencing was used to identify differentially expressed mi RNAs. A bioinformatics database was used to predict the target genes of differential mi RNAs, and Gene Ontology(GO), and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were conducted on the predicted target genes. RESULTS: As compared to the CG group, the MG group's heart rate, heart volume, heart index, AST, CK, CK-MB, LDH, α-HBD, myocardial fiber thickness, and collagen fiber significantly increased, all P < 0.01, while following QYN, these indicators improved in the HD group, all P < 0.01 or P < 0.05. Compared to the CG group, the MG group identified 151 differentially expressed mi RNAs, with 42 mi RNAs downregulated and 109 mi RNAs upregulated;compared to the MG group, the HD group identified 70 differentially expressed mi RNAs, 40 were downregulated, and 30 were upregulated. The GO functions of differential mi RNA target genes are mostly enriched in cardiac development regulation, cardiac contraction control, heart rate regulation, and so on. The most enriched KEGG pathways include the mitogenactivated protein kinase, Erb B, Hippo, forkhead box protein O, and Wnt signaling pathways. CONCLUSION: QYN may protect the cardiac structure and function and minimize cardiac damage caused by GD by regulating relevant target genes and signaling pathways through mi RNAs which include mi R-206-3p, mi R-122-5p, and mi R-200a-3p.
