Abstract:

Objective An exploration of the molecular mechanism of microRNA-146a （miR-146） intervention in Sepsis-induced cardiomyopathy（SIC） using P38MAPK/NF-κB. Methods SD rats were divided into four groups by the random number table method： the normal control group， the SIC model group， the miR-146a agonist group， and the miR-146a inhibitor group. Rats in the normal control group and SIC model group were injected intraperitoneally with 0.2 μL/g saline， rats in the miR-146a agonist group were injected intraperitoneally with 0.2 μL/g miR-146a agonist， rats in the miR-146a inhibitor group were injected intraperitoneally with 0.2 μL/g miR-146a inhibitor； 24 h later， rats in the SIC model group， miR-146a agonist group， and miR-146a inhibitor group were injected intraperitoneally with lipopolysaccharide （LPS） to prepare the SIC rat model， and the normal control group was injected with an equal amount of saline.Histopathological morphology was observed by HE staining； apoptosis rate of cardiomyocytes was detected by TUNEL； cardiac troponin I （cTnI） and B-type brain natriuretic peptide （BNP） contents were detected by ELISA； creatine kinase cardiac muscle binding （CK-MB） and myoglobin （Mb） contents were detected by chemiluminescence； p38 mitogen activation in rat myocardial tissue was detected by Western blot protein kinase （p38MAPK）， nuclear factor-kB （NF-κB）， tumor necrosis factor-α （TNF-α） and intercellular adhesion molecule-1 （ICAM-1） by Western-Blot； miR-146a， TNF-α， interleukin-1α （IL-1α） and interleukin-1β （IL-1β） mRNA by reverse transcription quantitative （RT-q） PCR. Results Myocardial cells in the normal control group were uniform in size， neatly arranged， with distinct transverse lines， and had normal structure； myocardial cells in the SIC model group and miR-146a inhibitor group were disordered， with myocardial fibers fragmented and expanded at intervals. Myocardial structural damage was minimized in the miR-146a agonist group compared to the SIC model group. Compared with the normal control group， the apoptosis rate， serum cTnI， BNP， CK-MB， Mb levels， myocardial tissue p-p38 MAPK， p-NF-κB p65， TNF-α， ICAM-1 protein expression levels， TNF-α， IL-1α， miR-146a mRNA levels were significantly higher in the SIC model group， miR-146a agonist group and miR-146a inhibitor group， IL-1β mRNA levels were significantly increased and miR-146a mRNA levels were decreased. Compared with the SIC model group， the apoptosis rate， serum cTnI， BNP， CK-MB， Mb levels， myocardial tissue p-p38 MAPK， p-NF-κB p65， TNF-α， ICAM-1 protein expression in the miR-146a agonist group of rats levels， TNF-α， IL-1α， IL-1β mRNA levels were significantly reduced， and miR-146a mRNA levels were increased. Conclusion miR-146a has the ability to modulate the p38 MAPK/NF-κB signaling axis and the release of inflammatory factors.High miR-146a expression has some negative influence on the inflammatory response， reducing the onset and development of the inflammatory response while improving it. It can offer SIC early intervention therapy with a pre-study mechanism and theoretical support.

Key words: septic cardiomyopathy, miR-146a, P38MAPK, NF-κB