Study on the Relationship Between Changes in Heparin-Binding Protein Levels and Coagulation Disorders and Vascular Endothelial Injury in a Rat Model of Sepsis

doi:10.12300/j.issn.1674-5817.2025.182

Abstract

Abstract:

Objective To observe the dynamic changes in heparin-binding protein (HBP), coagulation function indicators, and vascular endothelial injury markers in SD rats with sepsis, analyze the associations among these indicators, and elucidate the regulatory role of HBP in sepsis-associated coagulation disorders. Methods Eighteen specific pathogen-free (SPF) male SD rats aged 8–12 weeks were selected to establish a sepsis model using cecal ligation and puncture (CLP). Blood samples were collected from the heart at 0 hours before modeling and at 3, 6, and 9 hours post-modeling. Thromboelastography (TEG) with standard and heparinase cups was used to determine the difference in reaction time (R value) between the two cups (ΔR), thereby evaluating coagulation function and the endogenous heparin effect. Plasma levels of HBP, heparan sulfate (HS), syndecan-1 (SDC-1), and thrombomodulin (TM) were measured by enzyme-linked immunosorbent assay (ELISA). Samples with ΔR≥2 min were grouped as the ΔR≥2 min group, while those with ΔR<2 min were grouped as the ΔR<2 min group. Correlation and receiver operating characteristic (ROC) curve analyses were performed to evaluate the relationship between HBP and various indicators, as well as its predictive efficacy for ΔR values. Results ΔR, HS, SDC-1 and HBP significantly increased after modeling compared with 0 hours (P<0.01). The HS, SDC-1, and HBP levels in the ΔR≥2 min group were significantly higher than those in the ΔR<2 min group (P<0.05 or P<0.01). HBP showed a significant positive correlation with ΔR and HS (P<0.05), while ΔR was significantly positively correlated with HS (r=0.799, P<0.01) and weakly positively correlated with SDC-1 (r=0.289, P<0.05). HS, HBP, and SDC-1 demonstrated significant predictive value for ΔR≥2 min (P<0.01). Conclusion In the early stages of sepsis, the release of HS-like anticoagulant substances from the glycocalyx following its degradation can lead to coagulation disorders, while HBP can reflect the pathological process and play an important regulatory role in the occurrence and development of sepsis-related coagulation disorders.

Key words: Sepsis, Heparin-binding protein, Heparan sulfate, Thromboelastography, Endothelial injury, SD rats

CLC Number:

R631
R-332

TIAN Yan,LAI Dong,LAI Fei,et al. Study on the Relationship Between Changes in Heparin-Binding Protein Levels and Coagulation Disorders and Vascular Endothelial Injury in a Rat Model of Sepsis[J]. Laboratory Animal and Comparative Medicine, 2026, 46(5): 700-706. DOI: 10.12300/j.issn.1674-5817.2025.182.

Figures/Tables 4

References 21

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指标 Index	建模后时间/h Post-modeling time/h
指标 Index	0	3	6	9
HS ρ/(ng·mL^-1)	6.67 (5.60, 11.26)	6.74 (5.58, 10.01)	15.62 (10.63, 21.56)^**	14.43 (8.37, 18.43)^**
TM ρ/(ng·mL^-1)	6.13 (4.43, 10.58)	6.18 (2.31, 10.19)	7.54 (4.46, 10.87)	5.02 (2.04, 6.33)
SDC-1 ρ/(ng·mL^-1)	14.42 (11.48, 18.99)	16.34 (12.13, 19.24)	23.89 (18.01, 26.70)^**	21.88 (15.10, 25.77)^**
ΔR t/min	0.35 (0.08, 0.90)	0.65 (0.38, 3.25)^*	3.55 (2.45, 5.00)^**	3.00 (2.00, 3.70)^**
HBP ρ/（pg·mL^-1）	152 (115, 226)	326 (262, 417)^**	387 (263, 493)^**	342 (222, 486)^**

指标 Index	建模后时间/h Post-modeling time/h
指标 Index	0	3	6	9
HS ρ/(ng·mL^-1)	6.67 (5.60, 11.26)	6.74 (5.58, 10.01)	15.62 (10.63, 21.56)^**	14.43 (8.37, 18.43)^**
TM ρ/(ng·mL^-1)	6.13 (4.43, 10.58)	6.18 (2.31, 10.19)	7.54 (4.46, 10.87)	5.02 (2.04, 6.33)
SDC-1 ρ/(ng·mL^-1)	14.42 (11.48, 18.99)	16.34 (12.13, 19.24)	23.89 (18.01, 26.70)^**	21.88 (15.10, 25.77)^**
ΔR t/min	0.35 (0.08, 0.90)	0.65 (0.38, 3.25)^*	3.55 (2.45, 5.00)^**	3.00 (2.00, 3.70)^**
HBP ρ/（pg·mL^-1）	152 (115, 226)	326 (262, 417)^**	387 (263, 493)^**	342 (222, 486)^**

指标 Index	ΔR≥2 min组/n=26 ΔR≥2 min group/n=26	ΔR＜2 min组/n=46 ΔR＜2 min group/n=46	z	P
HS ρ/(ng·mL^-1)	18.43（5.73, 21.99)	8.07（5.75, 15.87)	-2.537	0.011
TM ρ/(ng·mL^-1)	6.23（4.08, 10.19)	5.70（2.04, 6.45)	-1.559	0.119
SDC-1 ρ/(ng·mL^-1)	25.88（23.10, 27.77)	16.73（13.11, 22.63)	-4.628	0.000
ΔR t/min	3.00（2.18, 3.70)	0.00（-0.23, 0.53)	-3.936	0.000
HBP ρ/（pg·mL^-1）	363（322，498）	122（111，204）	-6.875	0.000

指标 Index	ΔR≥2 min组/n=26 ΔR≥2 min group/n=26	ΔR＜2 min组/n=46 ΔR＜2 min group/n=46	z	P
HS ρ/(ng·mL^-1)	18.43（5.73, 21.99)	8.07（5.75, 15.87)	-2.537	0.011
TM ρ/(ng·mL^-1)	6.23（4.08, 10.19)	5.70（2.04, 6.45)	-1.559	0.119
SDC-1 ρ/(ng·mL^-1)	25.88（23.10, 27.77)	16.73（13.11, 22.63)	-4.628	0.000
ΔR t/min	3.00（2.18, 3.70)	0.00（-0.23, 0.53)	-3.936	0.000
HBP ρ/（pg·mL^-1）	363（322，498）	122（111，204）	-6.875	0.000