Cotinine inhibits TLR4/NF-κB signaling pathway and improves deep vein thrombosis in rats

Background: The present study was designed to explore the regulatory mechanisms and influences of cotinine on deep vein thrombosis (DVT) in rats via the toll-like receptor 4/nuclear factor kappa binding (TLR-4/NF-kappa B) pathway. Methods: In this experimental study, 30 SD rats were randomly assigned to control group, sham operation group, model group, cotinine (10 mu g/kg) group, and model + cotinine (10 mu g/kg) group. The thromboxane B2 (TXB2), 6-keto-PGF(1 alpha), plasminogen activator inhibitor (PAI), tissue plasminogen activator (t-PA), TLR4, NF-kappa B, and p65 mRNA and protein expression and tissue changes were analyzed by ELISA, Hematoxylin-Eosin (HE) staining, RT-PCR, andWestern blot. Results: There was no significant difference between the control and sham operation groups (P>0.05). The model and cotinine groups showed significantly higher mRNA and protein levels of TXB2, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), PAI, TLR-4, and NF-kappa B, and significantly lower levels of 6-keto-PGF(1 alpha) and t-PA than the control and sham operation groups (P<0.05), and the model + cotinine group showed significantly higher mRNA and protein levels of TXB2, IL-6 and TNF-alpha, PAI, TLR-4, and NF-kappa B and significantly lower levels of 6-keto-PGF(1 alpha) and t-PA than the model group (P<0.05). Conclusion: Cotinine can aggravate thrombus and inflammation in rats with DVT, and the mechanism may be associated with the activation of the TLR-4/NF-kappa B inflammatory signaling pathway.