Study On The Characteristics Of Blood Physiological Function Of Double Indole Fibrinolytic Compounds FGFC1

In recent years,with the improvement of people's diet and social aging,the incidence and the mortality of cerebrovascular disease in China,showed a linear upward trend,cerebrovascular disease always has a close relationship with thrombosis and thrombosis embolization.Thrombolytic drugs on the market have been developed to the third generation,but can not completely solve the problems caused by thrombosis,drug researchers around the world are actively looking for new drug treatment direction,and the found of small molecule fibrinolytic compounds brings hope to this situation.Based on the unique thrombolytic properties of FGF1(Fungi fibrinolytic compound 1)isolated from marine microbes,stachbotrys longispora FG216,investigated the effect of FGFC1 on the physiological characteristics of erythrocytes.evaluated the allergic effects of FGFC1 and the long-term toxicity studies were by systemic active hypersensitivity test and passive skin allergy test.provides reliable data support to FGFC1 preclinical safety evaluation.The first chapter summarizes the composition and function of fibrinolytic system,the factors of thrombosis,the classification and the thrombolytic mechanism of thrombolytic drugs.In the second chapter,the thrombolytic effect of FGFC1 was verified by in vitro thrombolysis and pulmonary thrombus model.In vitro thrombolysis experiments showed that the EC50 of the marine double indole fibrinolytic compound FGFC1 was 7?mol/L and showed specific fibrinolytic activity at 5 ~ 50?mol/L.In vivo FITC-fibrinogen degradation experiments showed that 10mg/kg of FGFC1 could degrade acute pulmonary thrombosis in rats,and its thrombolytic effect was similar to that of 2.7mg/kg pro-uPA.Chapter three is to study the effect of FGFC1 on the physiological characteristics of erythrocytes.0.015 mg / mL FGFC1 no obvious hemolysis or agglomeration during the observation period of 3h after injection,indicating no hemolytic effect on rabbit red blood cells.The effect of FGFC1 on the physiological structure and characteristics of erythrocytes was determine by CAT,MDA,Na +-K +-ATPase activity in red blood cells and SC as negative control,DSS and SDS as positive control.The results showed that the concentration of FGFC1 was 0.3?g / mL-1.5?g / mL,CAT activity was 26.6485U/mL-51.0387U/mL,MDA content was 1.0112nmol/mL-5.6181nmol/mL.Na+-K+-ATPase Vitality of 790.65U/gHb-31876.94U/gHb.And the negative control group showed no significant difference,indicating that FGFC1 on the physiological structure of red blood cells without damage to the physiological characteristics of no significant impact.Chapter four will evaluate the allergic nature of FGFC1.The animal symptoms after dose were evaluated by guinea pig ASA test,and measured the levels of IgE and histamine.The serum histamine content in the FGFC1 low dose group was 6.48 mg / L,the IgE content was 5.98?g / mL,the serum histamine content in the high dose FGFC1 group was 6.97 mg / L and the IgE content was 6.68?g / mL.And the liver,small intestine and spleen of the experimental guinea pigs were subjected to histopathological examination.The results showed that the ASA test results of FGFC1 were negative.In the PCA test,the serum histamine content in the FGFC1 low dose group was 0.32 mg / L,content of IgE was 1.49?g / mL,0.46 mg / L in FGFC1 high dose group serum histamine,content of IgE was 1.60?g / mL.The size and optical density of the skin were measured.The optical density of the locus coeruleus was 0.86 in the high dose group and 0.66 in the low dose group.The results also showed that the PCA test results of FGFC1 were negative.It can be seen that FGFC1 no harm to the blood,the body without sensitization risk.The fifth Chapter is to study the long-term toxicity of FGFC1.After 21 days of continuous intraperitoneal administration,there was no significant effect on the natural growth of mice.The results of the blood index test showed,WBC?Hb?HCT?MCV?MCH?MCHC of FGFC1 treatment group hematological indicators are within the normal range,PLT?MO?BAS?MPV?PCT?RDW of FGFC1 treatment group significantly higher than the blank control group,absolute value of NE?LYM?PDW of FGFC1 treatment group significantly lower than the blank control group.The liver slices of the mice showed that the high dose group of FGFC1 had some damage to the liver of the mice,but the damage was reduced to no effect as the concentration decreased.Resulting in liver damage and blood indicators have the reason for such a deviation,remains to be further studied.