Effect of plasminogen activator inhibitor-1 inhibitors on the severity of traumatic femoral head necrosis in rats
GAO Yang
DONG Hai-peng
WANG Wen-juan
LIU Feng
LIU Chao
Abstract：Objective To investigate the effect of plasminogen activator inhibitor-1(PAI-1)inhibitors on plasma levels of active PAI-1 and the severity of postoperative femoral head necrosis in a rat model of traumatic femoral head necrosis.Methods A total of 60 rats were used to establish a rat model of traumatic femoral head necrosis and were randomly divided into 3 groups:PAI-1 inhibitor group,PAI-1 group,and blank control group(20 rats in each group).In the PAI-1 inhibitor group,rats were intraperitoneally injected with the PAI-1 inhibitor tiplaxtinin(1 mg/kg)6 hours after surgery,followed by oral administration of Tiplaxtinin[2 mg/(kg?d)]for 4 weeks.In the PAI-1 group,rats received an intraperitoneal injection of exogenous PAI-1(2.5 nmol/kg)every 3 days after surgery.The blank control group received an equivalent volume of normal saline.Plasma levels of active PAI-1 were measured using an ELISA method at preoperative,6 hours,12 hours,24 hours,and 4 weeks postoperatively.At the end of the experi-ment,the right femoral heads of the rats in each group were evaluated for femoral head necrosis using micro-CT and H&E staining.Results In the PAI-1 inhibitor group,two rats experienced postoperative bleeding,and in the blank control group,one rat had an infection.Plasma levels of active PAI-1 in the blank control group and the PAI-1 inhibitor group were significantly elevated at 6 hours postoperatively and then significantly decreased over time(P＜0.01).In the PAI-1 group,plasma levels of active PAI-1 were significantly increased at 6 hours postoperatively(P＜0.01),but there was no significant decrease in plasma levels of active PAI-1 in the later stages(P＞0.05).There were no significant inter-group differences in plasma levels of active PAI-1 between the PAI-1 inhibitor group and the PAI-1 group at 6 hours postoperatively compared to the blank control group(P＞0.05).However,at 12 hours,24 hours,and 4 weeks postoper-atively,plasma levels of active PAI-1 were significantly increased in the PAI-1 group compared to the blank control group,while they were significantly decreased in the PAI-1 inhibitor group(P＜0.01).Regarding the evaluation of femoral head necrosis,compared to the blank control group,the PAI-1 inhibitor group showed significantly increased bone volume fraction and trabecular thickness(P＜0.05)and significantly decreased trabecular separation,bone marrow cavity rate,and adipose tissue area(P＜0.05).The PAI-1 group exhibited significantly decreased bone volume fraction and trabecular thickness(P＜0.05)and significantly increased trabecular separation,bone marrow cavity rate,and adipose tissue area(P＜0.05)compared to the blank control group.When comparing the PAI-1 inhibitor group to the PAI-1 group,the former showed significantly decreased bone volume fraction and trabecular thickness(P＜0.05)and signifi-cantly increased trabecular separation,bone marrow cavity rate,and adipose tissue area(P＜0.05).Conclusion In a rat model of traumatic femoral head necrosis,plasma levels of active PAI-1 were found to be an important risk factor for traumatic bone necrosis.The use of PAI-1 inhibitors effectively reduced plasma levels of active PAI-1 and the severity of traumatic femoral head necrosis in rats.
Keywords：femoral neck fracturestraumatic femoral head necrosisPAI-1 inhibitoranimal models
Publication Date：2023-12-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 1479-1484 )