TXNIP activates NLRP3/IL-1ß and participate in inflammatory response and oxidative stress to promote deep venous thrombosis.

Increasing evidence indicates that deep venous thrombosis (DVT) is a common peripheral vascular disease. This study aims to investigate the mechanisms of thioredoxin-interacting protein (TXNIP) and nod-like receptor protein 3 (NLRP3) inflammasome in deep venous thrombosis (DVT). A total of 66 Sprague-Dawley (SD) rats were employed to conduct DVT model. DVT rat was treated with silenced TXNIP (si-TXNIP) lentivirus and MCC950 (a NLRP3 inhibitor). The thrombosis weight and weight/length ratio, tissue factor, inflammatory factors, superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were measured. Hematoxylin-eosin (H&E) staining was used to investigate the pathological change. Western blotting was used to determine the protein expression level. The expression level of thioredoxin (TRx) was suppressed, whereas TXNIP and NLRP3 were elevated in DVT rat. Si-TXNIP or MCC950 could reduce the thrombosis weight and weight/length ratio, ameliorate the pathological change, and decrease inflammatory reaction. Mechanistically, si-TXNIP or MCC950 inhibited the expression levels of TXNIP, NLRP3, and interleukin (IL)-1ß while elevating the TRx level, thereby suppressing the DVT. Our study indicated that si-TXNIP or MCC950 injection rescued the injury of vein induced by DVT. The possible mechanisms connected with the inhibition of TXNIP and NLRP3. TXNIP is a possible therapeutic target for DVT.

Sulforaphane alleviates lung ischemia­reperfusion injury through activating Nrf­2/HO­1 signaling.

Oxidative stress and inflammation are both involved in the pathogenesis of lung ischemia-reperfusion (I/R) injury. Sulforaphane (SFN) is a natural product with cytoprotective, anti-inflammatory, and antioxidant properties. The present study hypothesized that SFN may protect against lung I/R injury via the regulation of antioxidant and anti-inflammatory-related pathways. A rat model of lung I/R injury was established, and rats were randomly divided into 3 groups: Sham group, I/R group, and SFN group. It was shown that SFN protected against a pathological inflammatory response via inhibition of neutrophil accumulation and in the reduction of the serum levels of the pro-inflammatory cytokines, IL-6, IL-1ß, and TNF-α. SFN treatment also significantly inhibited lung reactive oxygen species production, decreased the levels of 8-OH-dG and malondialdehyde, and reversed the decrease in the antioxidant activities of the enzymes catalase, superoxide dismutase, and glutathione peroxidase in the lungs of the I/R treated rats. In addition, SFN ameliorated I/R-induced lung apoptosis in rats by suppressing Bax and cleaved caspase-3 levels and increased Bcl-2 expression. Furthermore, SFN treatment activated an Nrf2-related antioxidant pathway, as indicated by the increased nuclear transfer of Nrf2 and the downstream HO-1 and NADPH quinone oxidoreductase-1. In conclusion, these findings suggested that SFN protected against I/R-induced lung lesions in rats via activation of the Nrf2/HO-1 pathway and the accompanied anti-inflammatory and anti-apoptotic effects.

Resveratrol Ameliorates Deep Vein Thrombosis-Induced Inflammatory Response Through Inhibiting HIF-1α/NLRP3 Pathway.

Deep vein thrombosis (DVT) has become a prevalent and increasingly serious problem globally and resveratrol (Res) is a natural antitoxin that inhibits arterial thrombosis. To investigate the effect of Res on DVT and further explore its mechanism, thrombosis was monitored at different time points and the pathological changes occurring in the inferior vena cava (IVC) and lung tissue were observed in Sprague-Dawley rats. The protein expression of HIF-1α and NLRP3 in the IVC and lung tissue and the concentrations of D-dimer (D2D), prothrombin fragment 1 + 2 (F1 + 2), interleukin-1ß (IL-1ß), caspase-1, and tissue factor (TF) in the plasma were determined. After setting different doses of Res groups and using low-molecular-weight heparin (LMWH) as a positive control to determine the effective experimental dose of Res, rats were further divided into sham, DVT, HIF-1α inhibitor, Res, and HIF-1α inhibitor + Res groups. The above indicators were tested repeatedly. The DVT was formed on the 1st day of modeling. With the extension of time, DVT was gradually institutionalized and finally recanalized. Lesions in the IVC and lung tissue were effectively ameliorated, and thrombosis was significantly decreased in the LMWH or 60 mg/kg Res-treated groups. The levels of D2D, F1 + 2, IL-1ß, caspase-1, TF, and the expression of HIF-1α and NLRP3 were significantly reduced in the HIF-1α inhibitor, Res, and HIF-1α inhibitor + Res groups. Res can ameliorate DVT in rats by inhibiting HIF-1α/NLRP3 pathway, which provides a novel therapeutic strategy for DVT treatment.