Toll-like receptor 4uclear factor-kappa B pathway is involved in myocardial injury in a rat chronic stress model.

摘要

Chronic stress is considered to predispose to various cardiovascular events such as coronary artery disease, hypertension, and even heart failure. In this study, rats were exposed to stress for 1 day, 1, 2, 3, and 4 weeks to establish a chronic stress model. A specific toll-like receptor 4 (TLR4) antagonist eritoran was used to block the activity of TLR4. On the second day after the last stress exposure, the animals were killed. The expression of TLR4 mRNA and nuclear factor-kappa B (NF-kappaB) DNA-binding activity in the myocardium were measured using reverse transcriptase polymerase chain reaction and electrophoretic mobility shift assay. The proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL-6) in myocardium were assayed by enzyme-linked immunosorbent assay. Myocardial injury was evident after chronic stress for 2 weeks. The TLR4 mRNA expression reached a peak after stress for 1 week. It was sustained at a stable level after stress exposure for 3 weeks and was restored to a nearly normal level in the fourth week. NF-kappaB DNA-binding activity was significantly enhanced after the stress for 1 day and markedly enhanced again after a 2-week stress exposure. It was weakened and reached a normal level after stress exposure for 4 weeks. The levels of TNF-alpha and IL-6 gradually increased and reached peaks after stress for 4 weeks. Meanwhile, eritoran significantly decreased the TLR4 mRNA expression and NF-kappaB activity in rats from the 2-week stress group. However, it did not downregulate the levels of TNF-alpha and IL-6. Importantly, it significantly improved the myocardial injury induced by the chronic stress. In conclusion, TLR4/NF-kappaB participates in myocardial injury during chronic stress.