Expression and role of matrix metalloproteinases and tissue inhibitor of metalloproteinases in a rat model of traumatic deep vein thrombosis / 中国组织工程研究

ABSTRACT

BACKGROUND:The molecular mechanism of traumatic deep vein thrombosis is complex.Numerous studies focus on clinical observation and epidemiology,but its molecular mechanism has not been a new breakthrough.OBJECTIVE:By use of gene array technology,this study was aimed to study the expression changes of matrix metalloproteinases in rat models of traumatic deep vein thrombosis,and to explore the roles of matrix metalloproteinases in traumatic deep venous thrombosis.METHODS:A total of 150 SD rats,SPF grade,of 8-12 weeks old,body weight of 250-300 g,were divided at random into normal control group (n=10) and model group (n=140).Rat traumatic deep venous thrombosis models were set up by clamping the femoral vein and fixing the bilateral hind limbs,and the fixation of hip spica with plaster bandage was conducted in each group.Then rats were divided into 7 subgroups:post-traumatic 0.5 hours,post-traumatic 2.5 hours (initial period of thrombosis),post-traumatic 25 hours (thrombogenesis at thrombotic crest-time),post-traumatic 25 hours non-thrombogenesis at the thrombotic crest-time),post-traumatic 72 hours (thrombus resolution),post-traumatic 72 hours thrombus insolution) and post-traumatic 168 hours (nonthrombosis).At the corresponding phasess,the femoral vein tissues were incised,and total RNA of femoral vein was extracted using Trizol one-step method.Applying Genechip Rat Genome 430 2.0 genechips,the gene expressions in femoral vein were detected in different groups.The rate of traumatic deep venous thrombogenesis and non-thrombogenesis,the rate of thrombi solution and insolution were observed;the expressions of matrix metalloproteinases and tissue inhibitor of metalloproteinases at different time phases was detected by gene array data analysis.RESULTS AND CONCLUSION:Three model rats died and the remaining 147 rats were involved in the final analysis.At the post-traumatic 25 hours,the rate of thrombogenesis was 50.5% and nonthrombogenesis was 49.5%.To the post-traumatic 168 hours,the rate of thrombus solution was 56.7% and thrombus insolution was 43.3%.Both matrix metalloproteinases and tissue inhibitor of metalloproteinases exhibited differential expressions in the course of traumatic deep venous thrombosis.Under the thrombus insolution state,matrix metalloproteinases continued to show a high expression,tissue inhibitor of metalloproteinase expression was down-regulated in the thrombus formation,was significantly inhibited in the thrombus insoluUon process.In the process of traumatic deep vein thrombosis and insolution,matrix metalloproteinase was closely related to traumatic deep vein thrombosis,the matrix metalloproteinase/tissue inhibitor of metalloproteinases are likely to affect the biological state of thrombosis.