Study On Effects Of Therapy With Ardisia Gigantifolia Stapf Extract On Thrombosis In Vivo

Ardisia gigantifolia Stapf of Myrsinaceae genera, which is one of traditional Chinese herbal medicine, plays a role in invigorating blood circulation, eliminating stasis, etc. And it used to treat the wounded after a fall in the area of Yao minority in Southern China commonly. At present, experimental studies of Ardisia gigantifolia Stapf are rarely reported, especially, effects on thrombosis, dyslipidoses, microcirculation etc are not yet reported in domestic and abroad. Therefore, according to studies on effects of therapy with Chinese herbal medicine on thrombosis, dyslipidoses and microcirculation in domestic and abroad, three systemical trials were done.Trial 1 investigated effects of Ardisia gigantifolia Stapf extract on blood clotting system, lipid metabolism, hemorrheology and pulmonary injury in rat. 36 Sprague-Dawley (SD) rats were randomly divided into 6 groups(n=6 in each group), including the control, patho-model, PNS and 3 Ardisia gigantifolia Stapf -treated model groups of 10 g/kg, 5 g/kg, 2.5 g/kg crude drug. Except for the control group that was injected with 0.9%NaCl solution, all others were subcutaneously injected with adrenailne 0.08 mg/kg body weight (WB) once a day for 12 days to induce blood stasis and pulmonary injury. After patho-model was established, panax notoginseng saponins(PNS) and 3 Ardisia gigantifolia Stapf -treated model groups were intragastrically treated once a day for 12 days. Whereas the control and patho-model groups were administered with the same volume of 0.9% NaCl solution in the same way. After the model-treatment groups were treated, blood physiological and biochemical index were assayed, and lungs were removed en bloc and treated by 10% formalin for pathological test. This results showed that there was a significant change in prothrombin time(PT), activated partial thromboplastin time(APTT), blood 6 and 12 r/min shear rate viscosity, levels of fibrinogen(Fg) and malonaldehyde(MDA), activities of catalase(CAT) and superoxide dismutase(SOD), and alveolar septa width between the control and the patho-model groups (P<0.01, P<0.05). In addition, light microscopic viewing of the slides demonstrated a marked pulmonary injury in the patho-model group. When compared with the patho-model group, 10 and 5 g/kg groups significantly decreased blood 6, 12 and 30 r/min shear rate viscosity(P<0.01, P<0.05). In the model-treated group of 10 g/kg, a significant prolonged PT, thrombin time(TT) and APTT, and decrease in levels of MDA, Fg and triglyceride(TG), and also increase in activities of CAT and SOD were seen (P<0.01, P<0.05). The model-treated group of 10 g/kg obviously increased level of nitrogen monoxidum(NO) (P<0.05). Furthermore, HE staining showed that pulmonary injury was obviously improved in the 10 and 5 g/kg groups.Trial 2 investigated effects of Ardisia gigantifolia Stapf extract on blood clotting system, lipid metabolism and hemorrheology in rabbit. 48 rabbits were divided into 6 groups randomly (n=8 in each group), including the control, patho-model, PNS and 3 Ardisia gigantifolia Stapf extract-treated model groups of 15 g/kg, 10 g/kg, 5 g/kg crude drug. All groups, except for the control group that was injected with 0.9%NaCl solution, others were slowly injected intravenously with bovine serum albumin(BSA) (125 mg/kg WB) at 1, 5, 9, 13 days, and adrenaline was subcutaneously injected at 2, 3, 6, 7, 10,11, 14, 15 days, respectively to induce vascular endothelial cell (VEC) injury and a disorder of lipid metabolism according to a technique used by Van Winkle and Levy. After patho-model establishment, PNS and 3 Ardisia gigantifolia Stapf extract-treated model groups were intragastrically treated once a day for 10 days, whereas the control and patho-model group were administered with the same volume of 0.9% NaCl solution in the same way. Blood physiological and biochemical index were assayed. This results showed that there was a significant change in PT, APTT, levels of Fg, NO, MDA and SOD, platelets (PLT), mean cell volume (MCV), mean platelet volume(MPV), activities of coagulation factor V(FV:CA) and coagulation factorâ…¦(Fâ…¦:CA) between the control and the patho-model groups(P<0.01, P<0.05). When compared with the model group, the results also showed that 15 g/kg group significantly prolonged PT, TT and APTT (P<0.01), increased activities of CAT and SOD(P<0.05), and decreased levels of Fg, MDA and PMP, MCV and hematocrit(HCT) (P<0.01, P<0.05). In addition, 15 g/kg dose group decreased Fâ…¤:CA and Fâ…¦:CA significantly(P<0.01). Trial 3 investigated effects of Ardisia gigantifolia Stapf extract on the mesenteric microcirculation of SD rat. SD rats were dripped with noradrenaline(NA) of 10^-8 mol/L to induce disturbance of microcirculation, and effects of Ardisia gigantifolia Stapf extract on the changes of the mesenteric microcirculation of rat were observed before and after adrenaline was dripped. This results showed that there was a significant change in internal diameter of mesenteric arteriole, veinule and blood capillary, and mesenteric capillary count, mesenteric capillary blood flow and blood fluid state between the control and the patho-model groups(P<0.01, P<0.05). When compared with the patho-model group, It was found that Ardisia gigantifolia Stapf of 10 g/kg crude drug could improve internal diameter of mesenteric micrangium, especially internal diameter of mesenteric blood capillary (P<0.01, P<0.05). In addition, Ardisia gigantifolia Stapf of 10 g/kg crude drug could significantly improve mesenteric capillary count, capillary blood flow and blood fluid state(P<0.01, P<0.05).In short, Ardisia gigantifolia Stapf extract could significantly prolong PT, TT and APTT, decrease Fâ…¤:CA, Fâ…¦:CA, blood shear rate viscosity and level of Fg in vivo to inhibit intrinsic and extrinsic coagulation system, thus to prevent thrombogenesis and attenuate pulmonary tissue damage. Ardisia gigantifolia Stapf extract could obviously decrease MDA level, increase NO level, activities of CAT and SOD to stop lipid peroxidation and play an important role in antioxidation, thus to stabilize VEC and regulate dyslipidoses. In addition, Ardisia gigantifolia Stapf extract could significantly improve mesenteric micrangium, capillary count, capillary blood flow and blood fluid state to be effective in the treatment of disturbance of microcirculation.