ABSTRACT
Objective To explore the therapeutic effect and possible mechanisms of Xuebijing injection for treatment of rabbits with acute pulmonary thromboembolism (APTE). Methods Thirty-two New Zealand rabbits were randomly divided into normal control group, model group, low molecular weight heparin (LMWH) group and Xuebijing group by random number table, 8 rabbits in each group. APTE model was reproduced by re-infusing autologous blood clots, and nothing was done for the normal control group. After the model was established, intravenous injection of Xuebijing 1 mL/kg from ear marginal vein was given to the rabbits in Xuebijing group, the LMWH 100 U/kg was subcutaneously injected in LMWH group, the same amount of normal saline was given intravenously to model group and normal control group, twice daily for 7 days in all the groups. The changes of plasma D-dimer and endothelin-1 (ET-1) levels were detected by enzyme-linked immunosorbent assay (ELISA) after modeling for 8 hours and 1, 3, 5, 7 days;after 7 days the animals were sacrificed and their lung tissues were removed for the examination of ultrastructural changes under an electron microscope. Results With the prolongation of time, the D-dimer level in the model group was gradually increased, and on the 7th day after modeling, the level was significantly higher than that of the normal control, LMWH and Xuebijing groups (g/L:3.98±1.14 vs. 0.43±0.12, 1.05±0.13, 1.04±0.15, all P0.05). Electron microscopic examination of lung tissue ultra-structure showed:in the model group, there were the lung tissue basement membrane rupture, the organelle structure in vascular endothelial cells and alveolar epithelial cells typeⅠandⅡnot clear, disappearance of microvilli on cell surface, cytoplasm concentration, nuclear chromatin condensation, a lot of debris due to nuclear lysis, formation of apoptotic bodies after shedding, and mitochondrial structural damage. In LMWH group, the capillary endothelial cell swelling, a lot of necrotized blood cells oozing, blockage of lumen, the cytoplasm of typeⅡalveolar epithelial cell loose, edematous and multiple lamellar bodies vacuolized were seen. In Xuebijing group, capillary endothelial cell swelling, necrotized blood cells blocking the lumen and seeping, the link basically normal, the type Ⅱ alveolar epithelial cell edematous, mitigation of lamellar bodies emptying were found. Conclusions Xuebijing can significantly reduce the plasma D-dimer and ET-1 levels, adjust the balance of coagulation and fibrinolysis, simultaneously decrease the pulmonary vascular permeability obviously in rabbits with APTE, thus it possesses certain protective effect for endothelial function leading to amelioration of lung injury and reduction of lung pathological damage in rabbits with pulmonary embolism.
ABSTRACT
Objective To explore the therapeutic effect and possible mechanisms of Xuebijing injection for treatment of acute pulmonary thromboembolism(APE)in rabbits. Methods Twenty-four New Zealand rabbits with big ears were randomly divided into control group,model group and Xuebijing group(each n=8). The model of APE was performed by re-infusing of autologous blood clots. After the model was established,in the rabbits of the Xuebijing group,Xuebijing injection 1 mL/kg was injected into the ear marginal vein,twice daily for consecutive 7 days. In the model and control groups,the same amount of normal saline was given via the same route. The changes in plasma levels of B-type natriuretic peptide(BNP)were detected by enzyme-linked immunosorbent assay(ELISA) at the time points of 8 hours and 1,3,5,7 days,and after 7 days the lungs of the rabbits were removed for the lung histopathological examination. Results The BNP levels of the model group and Xuebijing group were significantly higher compared with the level of control group at 8 hours after embolization,the model group being the most significant(all P<0.05). On day 3,the BNP levels of the model group and Xuebijing group reached their peaks,and then gradually decreased,but the level of model group was significantly higher than that of Xuebijing group(ng/L:581.1±144.6 vs. 251.5±22.5,P<0.05). On day 7,the BNP level of Xuebijing group fell to the level of the control group(ng/L:78.5±9.4 vs. 50.9±11.5),the level of the model group also decreased,but it was still much higher than that of the Xuebijing group(ng/L:214.1±47.6 vs. 78.5±9.4,P<0.05). Histopathological examination showed Xuebijing could significantly reduce the infarct size with mild inflammatory cell infiltration,but the infarct size of the model group was obviously bigger than that of the Xuebijing group and accompanied by relatively more inflammatory cell infiltration. Conclusion Xuebijing injection can significantly reduce the plasma BNP level of the rabbits with pulmonary embolism,and in the mean time ameliorate the degree of inflammatory infiltration in the lung tissue and infarct.