Myocardial dysfunction is an important manifestation of
sepsis. In addition, inactivation of the
mitogen-activated protein kinase (MAPK) signaling pathway has been reported to be beneficial in
sepsis. The current study used gene expression profiling to demonstrate the overexpression of
angiotensin II type 1 receptor (AT1R) and activation of the MAPK signaling pathway in
sepsis. In this study, we used a rat model of
sepsis established by cecal
ligation and
puncture to explore the mechanism of AT1R silencing in relation to the MAPK signaling pathway on myocardial injury. Various parameters including blood pressure, heart rate, and cardiac function changes were observed.
Enzyme-linked
immunosorbent assay was used to measure the concentration of cardiac
troponin T (
TnT), cardiac
troponin I (cTnI), and
creatine kinase isoenzyme muscle/brain (CK-MB). Myocardial
enzyme, tissue
antioxidant capacity, mitochondria swelling, and membrane potential were also detected.
Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling staining was applied to measure cell apoptosis, and messenger RNA and
protein levels of apoptosis-related
proteins (
Fas ligand [Fasl], B-cell CLL/
lymphoma [Bcl-2], p53) were also detected. Initially,
sepsis rats exhibited decreased survival rate, but increased ejection fraction (EF), heart rate, and concentrations of
TnT, cTnI, and CK-MB. Furthermore, decreased AT1R expression inactivated the MAPK signaling pathway (shown as decreased
extracellular signal-regulated kinase and cyclic
adenosine 3',5'-monophosphate response element
binding protein expression), decreased EF, heart rate, and concentrations of
TnT, cTnI, and CK-MB, but increased
sepsis rat survival rate. Eventually, decreased AT1R expression inhibited myocardial cell apoptosis (shown as decreased apoptosis rate and p53 and Fasl expression as well as increased Bcl-2 expression). These findings indicated that AT1R silencing plays an inhibitory role in
sepsis-induced myocardial injury by inhibiting the MAPK signaling pathway.