| Objective: Under the guidance of the theory of nephron and qi and blood,and based on the pathophysiology of stress response,we observe the effect of Ginseng Sini Decoction on the formation of postoperative deep vein thrombosis(DVT)and explore its possible mechanism of action.Methods: The first part(clinical study): Using a randomized controlled double-blind method,the elderly patients who plan to undergo total knee replacement surgery were randomly divided into 2 groups,a drug treatment group(treatment group)and a heparin control group(control group).The treatment group took Ginseng Sini Decoction before the operation,and the control group took a placebo before the operation.After the operation,both groups of patients were injected with enoxaparin sodium for conventional anticoagulation therapy.The preoperative and postoperative stress response levels,the expression of inflammatory factors and coagulation factors,and the incidence of postoperative DVT in the two groups were observed.The second part(experimental research): Animal experiments were used to intervene with traditional Chinese medicine in rabbits before surgery to explore the prevention and treatment effects and possible mechanisms of postoperative DVT.The subjects of the study were old New Zealand rabbits,which were divided into a control group,a model group,a simple heparin group,and a traditional Chinese medicine intervention group.The traditional Chinese medicine intervention group was further divided into a low-dose group,a middle-dose group,and a high-dose group.Each group was given corresponding Chinese medicine or deionized water three days before modeling.After modeling,heparin alone group and traditional Chinese medicine intervention group were given heparin sodium for conventional anticoagulation therapy.Observe the stress response level,inflammatory factor expression,blood coagulation function and immune function status at different time points,evaluate the effect of preoperative Chinese medicine intervention on postoperative DVT in New Zealand old rabbits,and analyze and explore the possible mechanism of Chinese medicine.Results: Part ?: There was no significant difference in baseline data between the treatment group and the control group(P > 0.05).(1)Stress response level: Cortisol(COR)and adrenocorticotropic hormone(ACTH)in the treatment group on the first day after surgery were higher than those in the control group(P < 0.05),while blood glucose,COR and adrenocorticotropic hormone releasing hormone(CRH)in the treatment group on the third and seventh days after surgery were lower than those in the control group(P < 0.05).On the 7th day after operation,ACTH was lower than that of control group(P < 0.05).(2)Inflammatory cytokines: WBC count,C-reactive protein(CRP)and neutrophils percentage in the treatment group were lower than those in the control group on the 1st and 3rd day after surgery(P < 0.05).(3)Coagulation factor: the levels of D-dimer and fibrinogen in the treatment group decreased on the 1st and 3rd day after surgery(P < 0.05).(4)Lower extremity deep vein ultrasound examination: postoperative DVT occurred in 1 case(3.3%)of the treatment group and 8 cases(25.8%)of the control group,the incidence of DVT in the treatment group was lower than that in the control group(P < 0.05)).(5)VAS score: on the 3rd day after surgery,the VAS score of the treatment group was lower than that of the control group(P < 0.05).(6)Quality of postoperative recovery: on the 1st and 3rd day after surgery,the QOR-40 score of the treatment group was higher than that of the control group(P < 0.05).Part ?:(1)Stress response level: the levels of ACTH and COR in the medium-dose group were lower than those in the model group and the heparin group on the 3rd and 7th days after surgery(P < 0.05);On the 1st and 3rd day after surgery,the NE level in the medium-dose group was higher than that in the model group(P < 0.05),and on the 1st day after surgery,the NE level in the medium-dose group was higher than that in the heparin group(P < 0.05).On day 1 after surgery,?-Ep in medium dose group was higher than that in model group(P < 0.05),on day 3 and 7 after surgery,?-Ep in medium dose group was lower than that in model group(P < 0.05),and on day 7 after surgery,?-Ep in medium dose group was lower than that in heparin group(P < 0.05).On the 1st,3rd and 7th day after operation,the COR level in the TCM intervention group showed a gradually decreasing trend,and the COR level in the medium dose group was the most significant(P < 0.05).(2)Inflammatory cytokines: the levels of IL-6 and CRP in the medium-dose group were lower than those in the model group and the heparin group on the first and third days after surgery(P < 0.05);On the first day after surgery,the level of IL-8 in the medium-dose group was lower than that in the model group and the heparin group(P < 0.05),and on the third day after surgery,the level of IL-8 in the medium-dose group was lower than that in the model group(P < 0.05).(3)Coagulation factor: the levels of FIB,D-D and P-S in the TCM intervention group were all decreased on the 1st,3rd and 7th day after surgery,and the most significant on the 1st day after surgery in the medium-dose group(P < 0.05);(4)Immunoglobulin and T lymphocyte: Ig G,Ig A,Ig M,CD4+/CD8+ in the medium dose group were significantly increased on the 1st day after surgery(P < 0.05);CD3+ was significantly increased in the medium dose group on the third day after operation(P <0.05).(5)DVT screening of lower limbs: the incidence of TCM intervention group was10.00%,heparin group 25.00%,model group 45.00%,and the incidence of DVT in TCM intervention group was decreased(P < 0.05).(6)Western blot test: the RAS system and MAPK/NF-?B signaling pathway were activated after operation,while the RAS system and MAPK/NF-?B signaling pathway were inhibited to different degrees in the low-dose and medium-dose TCM intervention groups.(7)HE staining: in the medium-dose group,the structure of each layer of the lesion site was clear,no obvious inflammatory cell infiltration was observed,the venous wall was relatively complete,and there was a small amount of thrombus in the lumen.In the low-dose and high-dose groups,there were inflammatory cell infiltration and thrombosis in the veins.In the heparin group,inflammatory cell infiltration was obvious and thrombosis was observed in the veins.Conclusion:(1)Preoperative use of Ginseng Sini Decoction reduces the body's inflammatory response and coagulation status by regulating the perioperative stress response level,thereby reducing the incidence of postoperative DVT,and at the same time,improving the quality of postoperative recovery after the intervention of traditional Chinese medicine.(2)Preoperative Ginseng Sini Decoction intervention in New Zealand aged rabbits reduced the postoperative stress response level and inflammatory response,at the same time improved the coagulation status and immune function,reduced the incidence of postoperative DVT,RAS system and MAPK/NF-?B The different degrees of inhibition of signal pathways may be one of the effective mechanisms of traditional Chinese medicine intervention. |
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