胃酶抑素A在抗小鼠播散性白念珠菌感染中的作用  

Role of Secreted Aspartyl Protainase Inhibitor Pepstatin A in Disseminated Candida Albicans Infection in Mice

作　　者：李晶[1] 陈兴平[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院皮肤性病科,武汉430030

出　　处：《医药导报》2006年第9期865-868,共4页Herald of Medicine

摘　　要：目的评估分泌型天冬氨酸蛋白酶(Sap)抑制药胃酶抑素A(pepstatin A)在播散性白念珠菌感染中的治疗作用,并探讨Sap在小鼠播散性白念珠菌感染过程中的作用。方法制备播散性白念珠菌感染小鼠模型,不同剂量的胃酶抑素A应用于感染小鼠,观测其15 d内的存活情况;再以胃酶抑素A的最佳浓度0.6 mg.kg-1预先或感染后应用于小鼠,比较其15 d内的存活情况;均与氟康唑处理组、0.9%氯化钠溶液组进行比较。测定不同剂量的胃酶抑素A对小鼠肾菌落形成单位(CFU)的影响,进一步评估胃酶抑素A的抗白念珠菌活性。结果与0.9%氯化钠溶液组比较,胃酶抑素A的预防性用药对播散性白念珠菌感染小鼠有显著保护作用;最佳浓度为0.6 mg.kg-1,能显著延长感染小鼠的平均存活天数(P<0.01),提高存活率,其保护作用可达到使用1.0 mg.kg-1氟康唑的同等效果。0.6 mg.kg-1胃酶抑素A能显著减少白念球菌感染后第4天小鼠肾CFU。结论胃酶抑素A的预防性用药对播散性白念珠菌感染小鼠有显著保护作用,并间接提示Sap在播散性白念珠菌感染过程中有致病作用,且作用大部分发生在感染早期。Objective To evaluate the therapeutic effect of the Sap inhibitor pepstatin A and explore the role of secreted aspartyl protainase （Sap） in disseminated Candida albieans infection in mice. Methods A murine model of disseminated eandidiasis was developed with intraperitoneal injection of different doses of pepstatin A to deal with the mice. The survivors were observed within 15 days. The results from administration of optimal dose 0.6 mg·kg^-1 of pepstatin A prior to challenge and on days 1 to 4 postchanllenge were compared. And the Results were all compared with fluconazole control group. The efficacy of pepstatin A was evaluated by calculating the quantity of coloney-forming units（CFUs） in the kidneys. Results Pretreatment of neutropenic mice with pepstatin A afforded strong protection against disseminated candidiasis. The survival time of mice within 15 days was significantly prolonged than that receiving saline （P 〈 0.01） and the quatity of day-4 kidney CFUs was decreased. The optimal dose of pepstatin A was 0.6 mg·kg^-1 with a protective effect similar to the fluconazole at the dose of 1.0 mg·kg^-1. Conclusion This study shows the protective effect of pretreatment with pepstatin A in disseminated Cadida albincans infection and suggests that Saps play an essential role as virulence factors during early dissemination.

关 键 词：胃酶抑素A 白念珠菌 天冬氨酸蛋白酶 分泌型 

分 类 号：R977.3[医药卫生—药品] R965[医药卫生—药学]