Objective To investigate the mechanism of Huangqi Guizhi Wuwu Decoction in prevention and treatment of rats model with deep venous thrombosis (DVT).
Methods A total of 40 male SD rats with specific pathogen free (SPF) grade were randomly divided into sham operation group,model group,Chinese medicine group and heparin calcium group,with 10 rats in each group. Except for the sham operation group,the femoral vein thrombosis models of rats with incomplete ligation were established in the other three groups. In the Chinese medicine group,2.0 g/(kg·d) of freeze-dried powder solution of Huangqi Guizhi Wuwu Decoction was given by intragastric administration; in the heparin calcium group,351.43 IU/(kg·d) of low molecular weight heparin calcium was given by subcutaneous injection; in the sham operation group and the model group,distilled water was given by intragastric administration; the administration time for rats in each group was from 7 days before modeling to 7 days after modeling,once a day,lasting for 14 days. After treatment,the abdominal aorta blood of rats in each group was collected to detect the coagulation indicators such as activated partial thromboplastin time (APTT),prothrombin time (PT),thrombin time (TT),fibrinogen (FIB) and D-dimer (D-D),and the plasma metabolites were analyzed; the femoral vein segments of rats in each group were collected to observe the histomorphological differences of venous thrombosis segments.
Results Compared with the sham operation group,the levels of FIB and D-D in the model group increased significantly,and APTT,PT and TT shortened significantly (P < 0.05); compared with the model group,the FIB and D-D levels decreased significantly in the heparin calcium group and the Chinese medicine group,while APTT,PT and TT prolonged significantly (P < 0.05); compared with the heparin calcium group,the level of D-D in the Chinese medicine group was significantly lower (P < 0.05). Plasma metabolic analysis showed that there were 27 differential metabolites between the model group and the sham operation group; Huangqi Guizhi Wuwu Decoction could significantly restore 14 differential metabolites,involving the improvement of vitamin K,trimethylamine N-oxide (TMAO),anserine,L-carnosine,carnitine metabolism,bile acid metabolism and lipid metabolism; low molecular weight heparin could significantly restore 8 differential metabolites,involving TMAO,anserine,L-carnosine,carnitine metabolism and amino acid metabolism. Histomorphological results showed that there was no thrombosis in the venous lumen in the sham operation group; in the model group,the venous lumen was filled with thrombus,and the inflammatory cell infiltration was more serious; in the heparin calcium group,part of the thrombus in the venous lumen disintegrated,part of the thrombus contracted,and the inflammatory cell infiltration was lighter than that in the model group; in the Chinese medicine group,most of the thrombus in the venous lumen disintegrated and disappeared,a small amount of thrombus remained and contracted,and the inflammatory cell infiltration in the vascular wall was light,which indicated the degree of pathological damage was light.
Conclusion Huangqi Guizhi Wuwu Decoction has the effects of anticoagulation,improving metabolic disorder,inhibiting thrombosis,protecting vascular endothelial cells and reducing inflammatory cell infiltration,which may be the important mechanism for treatment of DVT.
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