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. 2020 Jun 26;40(6):BSR20201293.
doi: 10.1042/BSR20201293.

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

Zhiyuan Cheng  1 , Wei Jia  1 , Xuan Tian  1 , Peng Jiang  1 , Yunxin Zhang  1 , Jinyong Li  1 , Chenyang Tian  1 , Jianlong Liu  1
Affiliations

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

Zhiyuan Cheng et al. Biosci Rep. .

Abstract

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 κ binding (TLR-4/NF-κB) pathway.

Methods: In this experimental study, 30 SD rats were randomly assigned to control group, sham operation group, model group, cotinine (10 μg/kg) group, and model + cotinine (10 μg/kg) group. The thromboxane B2 (TXB2), 6-keto-PGF1α, plasminogen activator inhibitor (PAI), tissue plasminogen activator (t-PA), TLR4, NF-κB, and p65 mRNA and protein expression and tissue changes were analyzed by ELISA, Hematoxylin-Eosin (HE) staining, RT-PCR, and Western 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-α (TNF-α), PAI, TLR-4, and NF-κB, and significantly lower levels of 6-keto-PGF1α 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-α, PAI, TLR-4, and NF-κB and significantly lower levels of 6-keto-PGF1α 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-κB inflammatory signaling pathway.

Keywords: TLR4/NF-κB signal pathway; cotinine; venous thrombosis.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. HE dyeing experiment pictures
(A–E) HE staining (200×). (A) Control group, (B) Sham operation group, (C) Model group, (D) Cotinine group, (E) Model + Cotinine group.
Figure 2
Figure 2. The expression levels of related genes detected by RT-PCR
Compared with control group, οP<0.05; compared with sham operation group, •P<0.05; compared with model group, □P<0.05; compared with cotinine group, ▪P<0.05.
Figure 3
Figure 3. Western blot detection.
(A) Protein bands, (B) protein expression levels. (B) Compared with control group, οP<0.05; compared with sham operation group, •P<0.05; compared with model group, □P<0.05; compared with cotinine group, ▪P<0.05.
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