Expression And Significance Of Platelet-derived Growth Factor CC During Intravenous Thrombolysis

DVT is a common disease in vascular surgery, and the incidence has graduallyincreased, but the drug and operation treatment has many limitations, and the natureof the dissolution process of thrombosis and abnormal slow, leading to the incidenceof PTS is high, seriously affecting the quality of life of the patients, but also broughthuge economic burden.Therefore, it is essential in clinic to acquire a new therapywhich is a new more efficient and rapid technology to accelerating the recanalizationof venous thrombosis.It has been proved that angiogenesis is a critical step of recanalization ofthrombus. Neovascularization vein thrombus formation than arterial thrombosis ismore widely. A number of studies have found that a lot of promoting angiogenesisfactor, for example VEGF, bFGF, HGF, EGF all can participate in angiogenesis.PDGF-C is a growth factor PDGF/VEGF family recently discovered, the activatedform of PDGF-CC, with angiogenic ability strong, is a key pathologicalneovascularization factor, and the target is broad, the promotion of angiogenesis maynot depend on VEGF. At present, PDGF-CC is involved in the dissolution of venousthrombosis is unknown, this experiment focused on the expression and significance of PDGF-CC process of intravenous thrombolysis in rats, and PDGF-CC promote thethrombolytic effect, in order to provide new theoretical basis for the clinicaltreatment of VTE.PART I A NEW MODEL OF VENOUS THROMBOSIS OFINFERIOR VENA CAVA OF RATS AND MORPHOLOGICALSTUDY OF THE THROMBOSISObjective: Our aim was to produce a new model of Venous Thrombosis ofInferior Vena Cava of Rats which more closely simulated the conditions in whichthrombosis usually occurs in man,and study the process of thrombus resolution in ratmodel.Design and Methods: Experimental group(A group): The IVC of ten male SDrats was exposed as above. A caval stenosis was produced by a ligature placed belowthe left renal vein which was tightened until flow was reduced by a mean of80%-90%,damage the endothelium of the ICV,and the branch vein of ICV wasligated. Control group(B group C group D group): B group as same as A group,butthe branch vein of ICV was not ligated, C group no damage for the endothelium ofthe ICV,D group underwent sham operations.After24h, the animals were sacrificedand the thrombi weighed. Additional rats in A group, treated identically, inferior venacavography did at1,3,7,14,21, and28days after t hrombus generation， the ICVand thrombi were collected at1,3,7,14,21, and28days after thrombusgeneration，Paraffin sections were stained with haematoxylin and eosin. Results: The results obtained are summarized in the table below. There was nosignificant difference in animal weight between the control and experimental group.The weight of the thrombus in experimental animals were significantly more than thecontrol group (P*). Thromus was characterized microscopically and histologicallyand compared with clot formed by complete occlusion.The ICV venography in DSAshow the ICV of experimental group rats no flow and study the process of thrombusresoluti on，The relatively rapid (3–4weeks) rate of thrombus resolution in ratmodels may limit extrapolation to human thrombi that resolve slowly.Conclusion: This model is reproducible, technically simple. We believe thismore closely simulates the clinical situation in which venous thrombi occur and willallow further studies to be performed on thrombus resolution.PART II EXPRESSION AND SIGNIFICANCE OFPLATELET-DERIVED GROWTH FACTOR CC DURINGINTRAVENOUS THROMBOLYSISObjective：To explore the expression of platelet-derived growth factor CC(PDGF-CC) during intravenous thrombolysis in rats and the significance thereof.Methods：The inferior vena cava thrombosis model was established in adultmale SD rat, and control and experimental groups were set up. Specimens of inferiorvena cava and thrombus therein (n=12) were collected on day1,3,7,14,21and28after modelling. The expression of PDGF-CC protein and mRNA in inferior vena cava and thrombus during thrombolysis was determined by Western blotting andreal-time qPCR. The specimens of inferior vena cava and thrombi (n=3) of rats7days after modelling were collected to observe the pathohistological andimmunohistochemical changes.Results：Western blotting and real-time qPCR showed that PDGF-CC proteinand mRNA were expressed in inferior vena cava thrombi from1to28days aftermodelling, and the peak value of expression was found on day7(P<0.05). PDGF-CCprotein and mRNA were also expressed in the wall of inferior vena cava, but theexpression level was low and no significant difference was found between groups(P>0.05). Immunohistochemical analysis revealed that the specific expression ofPDGF-CC was present surrounding the new vessels in thrombi7days aftermodelling.Conclusions： PDGF-CC has been found to express in high level duringintravenous thrombolysis in rats, and it specifically expresses around the new vesselsin thrombi, implying that PDGF-CC may play an important role during intravenousthrombolysis.