World Journal of Emergency Medicine ›› 2025, Vol. 16 ›› Issue (4): 340-347.doi: 10.5847/wjem.j.1920-8642.2025.081
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Open Access
Li Wang1, Weihua Gong2(
)
Received:2024-05-29
Accepted:2024-11-20
Online:2025-07-18
Published:2025-07-01
Contact:
Weihua Gong
E-mail:weihuagong@zju.edu.cn
Li Wang, Weihua Gong. Bromodomain protein 4 inhibitor JQ-1 alleviates hepatic ischemia-reperfusion injury by blocking the NLRP3/caspase-1 pathway[J]. World Journal of Emergency Medicine, 2025, 16(4): 340-347.
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URL: http://wjem.com.cn/EN/10.5847/wjem.j.1920-8642.2025.081
Figure 1.
The expression of BRD4 and the serum levels of ALT and AST during hepatic I/R injury. A: Representative immunohistochemical staining of BRD4 in liver tissues. Magnification, 100×; scale bar, 100 μm. B: Quantification of immunohistochemical staining of BRD4 in liver tissues of mice from the sham and I/R groups. C, D: The concentration of serum ALT and AST in the sham group and the I/R group. BRD4: bromodomain protein 4; I/R: ischemia/reperfusion; ALT: alanine aminotransferase; AST: aspartate aminotransferase. ***P<0.001.
Figure 2.
Inhibition of BRD4 by JQ-1 protects against hepatic I/R injury. A: H&E staining and BRD4 immunohistochemical staining in liver tissues from the sham, I/R, and JQ-1 (50 mg/kg, i.p.) groups. Magnification, 100×; scale bar, 100 μm. B, C: Suzuki score and BRD4 relative expression of the sham, I/R, and JQ-1 groups of mice. D, E: The concentration of ALT and AST of the three groups. BRD4: bromodomain protein 4; I/R: ischemia/reperfusion; ALT: alanine aminotransferase; AST: aspartate aminotransferase. ***P<0.001, **P<0.01, *P<0.05.
Figure 3.
The cytoprotection activity of JQ-1 in vivo. Representative immunofluorescence staining of TUNEL (green) and DAPI (blue) in liver tissues of the sham, I/R and JQ-1 (50 mg/kg) groups. Magnification, 100×; scale bar, 100 μm. I/R: ischemia/reperfusion. **P<0.01.
Figure 4.
JQ-1 reduced the levels of pro-inflammatory cytokines and ROS in vitro. A: Cell proliferation ratio of RAW264.7 cells treated with JQ-1 at various concentrations for 24 h. B: The expression of IL-10 in the control, H2O2-induced, and H2O2+JQ-1 (500 nmol/L) groups for 24 h. C: The expression of IL-1β, IL-6 and IL-18 in the control, H2O2-induced, and H2O2+JQ-1 (500 nmol/L) groups for 24 h. D: The ROS level in RAW264.7 cells in the control, H2O2-induced, and H2O2+JQ-1 (500 nmol/L) groups for 24 h. ROS: reactive oxygen species; IL: interleukin; ***P<0.001, **P<0.01, *P<0.05.
Figure 5.
JQ-1 alleviate hepatic I/R injury by inhibiting the aggregation of NLRP3/caspase-1-positive macrophages. (A) Representative immunofluorescence staining of F4/80 (green), NLRP3 (red), and DAPI (blue) in liver tissues of the sham, I/R and JQ-1 (50 mg/kg) groups. Magnification, 100×; scale bar, 100 μm. (B) Representative immunofluorescence staining of F4/80 (green), Caspase-1 (red), and DAPI (blue) in liver tissues of the sham, I/R and JQ-1 (50 mg/kg) groups. Magnification, 100×; scale bar, 100 μm. ***P<0.001, **P<0.01, *P<0.05.
Figure 6.
JQ-1 alleviates hepatic I/R injury by blocking the NLRP3/caspase-1 pathway. The protein levels of TXNIP, NLRP3, and Cle-Caspase-1 of RAW264.7 cells in the control, H2O2-induced (300 μmol/L), and H2O2+JQ-1 (500 nmol/L) groups for 24 h. **P<0.01, *P<0.05.
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