摘要：
Objective Chronic stress is an important risk factor for atherosclerotic diseases. Our previous studies have shown that chronic unpredictable mild stress (CUMS) accelerates atherosclerosis and up-regulates TLR4/NF-kappa B expression in apoE(-/-) mice. However, TLR4/NF-kappa B signaling whether directly contributes to the development of atherosclerosis in CUMS mice is unclear. We hypothesized that the interference of TLR4/NF-kappa B can ameliorate CUMS-induced inflammation and atherosclerosis in apoE(-/-) mice. Methods ApoE(-/-) mice were exposed to 12 weeks CUMS. Ad-siRNA TLR4 was given by tail vein injection (10 mu l/mouse, every 5 days), and PDTC (an inhibitor of NF-kappa B) was given by intraperitoneal injection (60 mg/kg, once a day). Plasma corticosterone concentrations were determined by solid-phase I-125 radioimmunoassay. Atherosclerosis lesions in aortic sinuses were evaluated and quantified by IMAGEPRO PLUS. Western blotting was used to detect the expression of TLR4, NF-kappa B, and IL-1 beta in aortas of the mice. Plasma lipid profiles, IL-1 beta, TNF-alpha, and MCP-1 were measured by ELISA. Results Our results indicated that CUMS apoE(-/-) mice treatment with siRNA TLR4 significantly decreased atherosclerosis and down-regulated TLR4, NF-kappa B, and inflammatory cytokines. PDTC also remarkably reduced atherosclerosis and the levels of IL-1 beta, TNF-alpha and MCP-1 in plasma. However, Treatment with siRNA TLR4 or PDTC had no effect on plasma corticosterone levels, and lipid profiles. Conclusions TLR4/NF-kappa B pathway may participate in CUMS-induced atherosclerosis through activation of proinflammatory cytokines in apoE(-/-) mice. Our data may provide a new potential therapeutic target for prevention of CUMS-induced atherosclerosis.
