The Anti-hydatid Pharmacodynamics Screening Of Harmine Derivatives In Mice

Objective:To establish a drug screening platform used for observing the anti-Echinococcus granulosus activity of 4 kinds of harmine derivatives in mice to find efficient anti-Echinococcus granulosus drugs.Methods:First,according to propertie of drug,the characteristics of the anti-hydatid pharmacodynamics screening and literatures and experimental design to establish a drug screening platform used for observing the anti-Echinococcus granulosus activity of 4 kinds of harmine derivatives in mice,hoping to find efficient anti-Echinococcus granulosus drugs.Results:To establish anti-hydatid pharmacodynamics screening platform of harmine derivatives in mice as follows,by using mice model with E.g protoscoleces culture in vitro by intraperitoneal injection and applying B ultrasonic examination to modle of success,with albendazole（ABZ）and harmine（HM）as the positive control drugs,LD₅₀0 of harmine derivatives were determined by Bliss method,the dose planning was in accordance with LD₅₀,the drug intervention by intraperitoneal injection was 14 days in a row,to observe the effect of harmine derivatives to mean cyst weight and the cyst inhibition rate,the weight scoring method of the number and diameter of sac varied,histopathological changes of the cyst under both optical and electron microscope,histopathological changes in the liver and brain under optical microscope,the cytokines of IL-2,IL-4,IL-10,IL-17A,IFN-γ,TNF.The results of anti-hydatid pharmacodynamics screening of harmine derivatives in mice as follows,preparation of mouse model by using E.g protoscoleces culture in vitro by intraperitoneal injection,the modle success rate reached to 67%,after pharmacological intervention,the results of mean cyst weight show 4 kinds of derivatives all had significant differences compared with model group（P<0.05）,and had a better trend of inhibited hydatid disease in mouse growth with dose-effect relationship,which derivatives DH-004 high dose has the strongest inhibition,the cyst inhibition rate was 71.56%,next came the high dose of derivativesDH-330,DH-145,DH-109,the cyst inhibition rates were 66.91%,61.34%,52.97%.The weight scoring method of the number and diameter of sac varied results show that derivatives DH-004,DH-145,DH-330 had significant differences compared with model group（P<0.05）except for derivatives DH-109,which derivatives DH-145 high dose has the best effect,the weight scoring was 66.18,next came the high dose of derivativesDH-004,DH-330,the weight scoring were 66.10,66.00.In the result of histopathology,4 kinds of derivatives all had different degree inhibition of inflammation of the liver.The TEM show except for derivatives DH-109,derivatives DH-004,DH-145,DH-330 could damage the structure of vesicle of stratum germinativum.In the immunal celluai factors,derivatives DH-004 and DH-109 may be similar to the immunoregulation of anti-echinococcus granulosis,derivatives DH-145 and DH-330 may have similar immunoregulation.Conclusion:This study established a drug screening platform used for observing the anti-Echinococcus granulosus activity of 4 kinds of harmine derivatives in vivo,by the comprehensive evaluation and analysis of detection index,the result show that derivatives DH-004,DH-145,DH-330 had better effective against experimental infected echinocoecsis granulosis cyst in mice,but derivatives DH-109 may have weaker against experimental infected echinocoecsis granulosis cyst in mice.