1. MicroRNA-421 improves ischemia/reperfusion injury via regulation toll-like receptor 4 pathway
- Author
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Xue-Zhi Zhang, Jian Yao, Ming-Lei Guo, Yun-Qi Weng, and Lin-Lin Guo
- Subjects
Male ,0301 basic medicine ,Prospective Clinical Research Report ,medicine.medical_specialty ,Medicine (General) ,Myocardial ischemia ,Myocardial ischemia reperfusion injury ,mouse model ,Ischemia ,Myocardial Reperfusion Injury ,Inflammation ,Biochemistry ,Mice ,03 medical and health sciences ,0302 clinical medicine ,R5-920 ,Internal medicine ,microRNA ,medicine ,Animals ,TLR4 ,Myocardial infarction ,HMGB1 Protein ,Toll-like receptor ,business.industry ,Biochemistry (medical) ,Cell Biology ,General Medicine ,medicine.disease ,Mice, Inbred C57BL ,Toll-Like Receptor 4 ,MicroRNAs ,myocardial infarction ,030104 developmental biology ,inflammation ,Reperfusion Injury ,030220 oncology & carcinogenesis ,Cardiology ,microRNA-421 ,medicine.symptom ,business ,Reperfusion injury - Abstract
Objectives The objective was to investigate the effects of microRNA-421 against myocardial ischemia/reperfusion injury in C57BL/6 mice. Methods Male C57BL/6 mice (n = 27) were randomly divided into three groups: normal control (NC) group (sham-treated); I/R model group, which underwent the I30min/R24h model (ischemia for 30 minutes followed by reperfusion for 24 hours); and the miRNA group, which were injected with miR-421. Pathology was assessed by hematoxylin and eosin staining and myocardial infarct size was measured by triphenyltetrazolium chloride staining. The apoptosis rate was measured by TUNEL assay, and relative expression of toll-like receptor-4 (TLR4), Janus kinase 2 (JAK2), and signal transducer and activator of translation 3 (STAT3) was evaluated by immunohistochemistry. Interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, and high mobility group protein B1 (HMGB1) serum concentrations were measured by ELISA. Results Compared with the NC group, in the model group, the myocardial infarction was large; inflammatory cell infiltration was severe; apoptosis was enhanced; expression of TLR4, JAK2, and STAT3 was increased; and serum concentrations of IL-6, TNF-α, IL-10, and HMGB1 were significantly increased. In the miRNA group, the ischemia/reperfusion injury was significantly improved. Conclusions Overexpression of miRNA-421 could reduce ischemia/reperfusion inflammatory response, perhaps via inactivation of TLR4, JAK2, and STAT3.
- Published
- 2020