| Background: Disseminated intravascular coagulation (DIC) is a clinical syndrome characterized by both microvascular thrombosis, and diffuse hemorrhages, due to the widespread activation of coagulation , consumption of coagulation factors and the accentuation of intravascular fibrin formation. There is a high mortality in DIC because of its complicated pathogeny and changing pathogenetic condition.The treatment protocols of DIC have not been standardized yet. At present, the main methods of treatments are anticoagulation, alternative, anti-platelet aggregation and supports treatment on the basis of the control of primary disease. However, some clinical practice prove: there are some limitations in alternative, anti-platelet aggregation and anti-fibrinolytic treatment which can not be used in a large-scale clinical treatment. Anticoagulants such as antithrombin (AT), activated protein C (APC), tissue factor pathway inhibitor (TFPI) and complement C1 - inhibitor (C1-Inh), have therapeutic action to DIC, but they are still at the experimental stage and can not be applied to clinical treatment in a short term. Although unfractionated heparin (UFH) has obvious anticoagulation function, it has not been used widely because of the serious complications such as thrombocytopenia. We found a new way in treatment of DIC when the emergence of low-molecular-weight heparin (LMWH).Low-molecular-weight heparins(LMWH) are fragments of commercially available unfractionated heparin prepared by either chemical or enzymatic depolymerization processes . The LMWH has a sronger ability of anti-FXa,but a fewer ability of anti-FIIa, so it can stop the pathological activation of coagulation earlier in DIC. The LMWH has a more reliable degree of anticoagulation and fewer associated side effects(bleeding, thrombocytopenia, osteoporosis et al.) compared with UFH.The safety and efficacy of LMWH is superior to UFH. LMWH which has substituted UFH gradually in recent years is widely used in the prevention and treatment of a variety of thromboembolic diseases. There are some experiments on the role of LMWH in the treatment of DIC at home and abroad ,but not the study on its influence of experiment targets and the comparison of therapeutic effects, bleeding risk , and so on . As a result , LMWH has not been widely used in the clinical prevention and treatment of DIC yet .Objective: To establish the model of DIC in rabbits making use of rabbit brain powder (thromboplastin) extract, prove the role of LMWH in prevention and treatment of rabbits with DIC, and provide the experimental basis for clinical treatment of DIC in use of LMWH.Methods: In accordance with the relevant literatures, this experimental established the model of DIC in rabbits in use of 4% rabbit brain powder extract (3ml/kg) by intravenous injection. After the success of modeling ,we divided all the rabbits tested into two groups- the DIC model group and the LMWH treatment group. The rabbits in LMWH treatment group were given low-molecular-weight heparin calcium (Bo Pu Qing) 50IU/kg, 2 times/day, intraperitoneal injection ; the rabbits in DIC model group were given equal quantity normal saline by intraperitoneal injection. Then we tested the chemical examination of coagulation, anticoagulation and fibrinolytic function in rabbits both in DIC model group and in LMWH treatment group, and compared between two groups of animals in general status and renal pathological changes under light microscope.The results and discussion:1. The establishment of DIC model in rabbits: The rabbits in rabbit brain powder intervention group experience of shortness of breath, heart rate accelerated and lips mild cyanosis about 1-1.5h after intravenous injection of 4% rabbit brain powder. 2h later, the platelet count (PLT) and fibrinogen (FIB) of rabbits in rabbit brain powder intervention group were significantly decreased (p <0.05), activated partial thromboplastin time (APTT) was extended (p <0.05) compared with the rabbits of saline control group. For the rabbits in rabbit brain powder intervention group, the positive rate of plasma protamine vice- solidification test (3P test) was as high as 100%;the morphology of peripheral blood erythrocytes was spine-shaped or polygonal, debris> 2%; fibrin microthrombus formation were seen in renal tissue under light microscope. As a result, we have successfully established DIC model in rabbits with rabbit brain powder .2.Comparing the relevant chemical examination of rabbits both in DIC model group and in LMWH treatment group:a. While in the process of the entire experiment, the duration of abnormal vital signs of rabbits in LMWH treatment group were shorter than that in DIC model group. There are not organ dysfunction , obvious bleeding tendency and death in LMWH treatment group rabbits. Therefore, LMWH plays a good role in improving clinical symptoms of DIC in rabbits.b. There was no significant difference of PLT in two group of rabbits (p> 0.05).This proves that LMWH is different from UFH in the function of reduction of PLT . The LMWH can less cause thrombocytopenia.The side effects of LMWH such as bleeding are fewer , the use of it is more secure.c. The level of FIB in two group rabbits decreased in the initial stage of intravenous injection of rabbit brain powder extract. But 6h later,rabbits in LMWH treatment group had higher levels of FIB, while the level of FIB in rabbits of DIC model group was significantly lower than pre-exposure level,there was significant difference between the two groups (p<0.05). It shows that LMWH does well in reducing the over-activation of fibrinogen and fibrin thrombosis.d. Compared with the DIC model, the APTT of LMWH treatment group rabbits was prolonged, there was statistical differences between the two groups (p <0.05). That tells us , LMWH can be used only 2 times a day to ensure its stability , validity and convenience.e. There were micro-fibrin thrombosis in the kidneys of DIC model group rabbits, but LMWH treatment group rabbits had no significant micro-fibrin thrombosis in kidney. Therefore, LMWH can help the rabbits with DIC to prevent of micro-thrombosis.Conclusion:1. The use of rabbit brain powder (thromboplastin) extract to establish of animal models of DIC has less related factors to intervene, the price is low, the modeling is successful . So the model plays an important role in the experimental study on DIC,especially in the study on DIC caused by non-infection factors.2. LMWH can improve the general state of animals with DIC, has an exact effect of anticoagulant, can inhibit the fibrinogen activation and prevent the micro-thrombosis ,so it has a good therapeutic effect of DIC.3. LMWH is easy to use and has less side effects such as thrombocytopenia, so it can be used in the whole clinical course of DIC treatment. |
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