Effect of rosiglitazone on myocardial injury in septic rats through NF-κB pathway

S.-M. Zhang, X.-F. Cai, Y.-L. Ma, Q. Lu

Department of Emergency, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 175845897@qq.com

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• Pharmacology

INTRODUCTION: To explore the effect of rosiglitazone on myocardial injury in septic rats through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway.

MATERIALS AND METHODS: A total of 60 healthy adult female Sprague-Dawley (SD) rats were randomly divided into 4 groups, namely, group A (sepsis model group, n=15), group B (sham operation group, n=15), group C (sepsis model + 3 mg/kg rosiglitazone, n=15), and group D (sham operation group + 3 mg/kg rosiglitazone, n=15), respectively. After the sepsis model was successfully established, the rats were administered with 3 mg/kg rosiglitazone by gavage, with a gavage volume of 1 mL, once a day for a total of 3 days. Blood was taken from the abdominal aorta, while lactate dehydrogenase (LDH) and creatine phosphokinase kits were used to detect the levels of LDH and creatine phosphokinase in serum. Then, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was adopted to identify myocardial tissue apoptosis, hematoxylin and eosin staining (H&E) was applied to detect myocardial tissue morphology, and enzyme-linked immunosorbent assay (ELISA) was utilized to examine the protein expression level of tumor necrosis factor-alpha (TNF-α) in rat serum. Subsequently, the messenger ribonucleic acid (mRNA) level of TNF-α in myocardial tissues was measured via fluorescence quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) method, and the activity of NF-κB was detected by electrophoretic mobility shift assay (EMSA).

RESULTS: Compared with those in group A, apoptotic cells in group B and group D were notably increased (p<0.05). At 3 days after administration with rosiglitazone (3 mg/kg), apoptotic cells were markedly decreased (p<0.05). H&E staining results manifested that 3 mg/kg rosiglitazone prominently improved myocardial tissue morphology in rats. The protein level of TNF-α in serum, the mRNA expression level of TNF-α in myocardial tissues, and the activity of NF-κB in group C treated with rosiglitazone were lower than those in group A (p<0.05).

CONCLUSIONS: Rosiglitazone can alleviate myocardial injury in septic rats by suppressing the TNF-α expression and this process is associated with the regulation on the NF-κB signal transduction pathway.

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