| Acute liver injury?ALI?is characterized by massive death of hepatocytes in a short period,and in severe cases can progress to acute liver failure even being life-threatening.Evodiamine?ED?is a kind of natural active alkaloid isolated from evodia rutaecarpa.ED has a multi-target role to exert a wide range of pharmacological activities and has the potential to interfere with liver injury.However,the application of ED has been limited by the deficiency of low water solubility,short half-life and no-targeting effect.In this study,biocompatible evodiamine complex fullerol nanoparticles?ECFNP?were prepared to improve hepatoprotective efficacy of ED.This study conducted a preliminary evaluation of the physicochemical properties,pharmacodynamics and safety of ECFNP.The research mainly includes the following four parts:The first part was preparation and physicochemical properties of ECFNP.Objective:To prepare ECFNP and investigate the physicochemical properties.Methods:ECFNP was prepared and its physicochemical parameters were determined.Results:ECFNP was prepared,and its appearance was a pale yellowish brown suspension,which was spherical or quasi-spherical when observed under transmission electron microscopy.The particle size and zeta potential were423.90±26.12 nm and 43.47±1.20 mV,conductivity was 152.13±0.47?S/cm,pH was 5.41±0.02,surface tension coefficient was 38.64±0.52 10-3N/m,density was 1.02±0.00 g/cm3,kinematic viscosity and dynamic viscosity were 2.14±0.00 mm2/s and 2.18±0.00 mPa·s respectively,the refractive index was 1.3305±0.00.Conclusion:ECFNP was successfully prepared,and the physicochemical parameters of ECFNP were appropriate.The second part was the establishment the model of ALI.Objective:To screen the concentration of CCl4 and establish an ALI model suitable for efficacy evaluation.Methods:0.1%,0.2%,0.5%,1%and 2%volume concentration of CCl4 peanut oil solution was injected intraperitoneally for modeling.The liver injury was evaluated by examining the serum ALT and AST levels,liver index and liver pathological changes,and screen out suitable method for establishing ALI model.Results:All concentrations of CCl4 could cause pathological changes in the serum and liver indexes of mice,and the damage was more serious with the increase of concentration.The liver damage caused by 0.1%concentration of CCl4 was moderate.Conclusion:ALI model was successfully established by 0.1%concentration of CCl4,which was suitable for subsequent pharmacodynamic evaluation.The third part was the evaluation of hepatoprotective effect of ECFNP.Objective:To investigate the protective effect of ECFNP on ALI in mice.Methods:The ALI model of mice was replicated by intraperitoneal injection of CCl4,and the treatment group was given ED and ECFNP?calculated as ED 5mg/kg?by gavage for one week respectively.To compare the effects of ED and ECFNP intervention on serum ALT and AST,inflammatory factor TNF-?and IL-1?,as well as liver homogenate index of GSH,CAT,SOD and MDA.Pathological changes of liver were observed under light microscope.Results:ED and ECFNP reduced activity of serum ALT and AST,lowered TNF-?and IL-1?,decreased level of liver MDA and liver index,increased the levels of liver antioxidants including GSH,CAT and SOD,and mitigated the pathological injury of liver.What's more,ECFNP was more effective than ED.Conclusion:ECFNP improved the protective effect of ED on ALI in mice.The fourth part was the preliminary evaluation of the safety of ECFNP.Objective:To evaluate the safety of ECFNP.Methods:To evaluate the effects of ECFNP on changes of body weight,the appearance,index and pathologic change of organs?heart,spleen,lung,kidney?in mice.Results:ECFNP had no significant effect on mice body weight,appearance and index of organs.ECFNP did not cause pathological damage.Conclusion:ECFNP has certain safety.In conclusion,ECFNP was successfully prepared in this paper and its physicochemical parameters were measured.ECFNP improved the protective effect of ED on acute liver injury in mice,and ECFNP was safe in vivo. |
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