抑制阿萨希毛孢子菌脂筏形成后对其致病性的影响研究

摘要

Objective To investigate the relationships between inhibititing lipid raft formation and pathogencity of (Trichosporon asahii, T. asahii) in murine model. Methods Fifty mice were immunosuppressed and divided into 5 groups randomly on the basis of the different suspensions. The experimental groups were inoculated suspensions dealing with amphotericin B which concentrations were 0.2 μg/ml, 0.5μg/ml, 1.0μg/ml, 2.0μg/ml respectively, and the control group was not processed. The death of each group were written down within three weeks, and then the main viscera of the mice were examined by mycologic culture and histopathology. Finally the infection rate were counted. Results The fatality rate and infection rate of countrol group were 80%and 90%respectively. While the number of two groups dealing with amphotericin B which density were 1.0μg/ml, 2.0μg/ml was 37.5%to 20%and 50%to 40%respectively, and was signiifcantly less than the control group(P<0.05). In spite of the number of the other two groups which density were 0.2μg/ml, 0.5μg/ml was decreased, there was no remarkably difference compared with the control group(P>0.05). Histopathology showed acute pyogenous inlfammation and granuloma with arthrospores and mycelia in the tissues. Conclusion Inhibited the lipid raft formation by amphotericin B, the pathogencity of T. asahii decreased apparently. With the increasing of density of amphotericin B, the fatality rate and infection rate of mice decreased gradiently. It was indicated that inhibititing the lipid raft of T. asahii can result in lowering the pathogencity. This discovery provide a clue for a new target of anti-fungal drug.%目的：观察阿萨希毛孢子菌（Trichosporon asahii, T. asahii）脂筏形成被抑制后对其致病性的影响。方法建立小鼠免疫抑制模型，将50只小鼠随机分为5组，每组10只。实验组分别接种经0.2、0.5、1.0、2.0μg/ml两性霉素B处理的菌悬液，对照组接种正常生长的菌悬液。连续观察3周，统计不同组别小鼠致死率，同时将内脏进行组织真菌培养及组织病理检查，计算感染率。结果对照组致死率为80%，内脏感染率为90%。接种经浓度为1.0μg/ml、2.0μg/ml两性霉素B处理而破坏T. asahii脂筏的菌悬液后，致死率和感染率分别为37.5%、20%以及50%、40%，与对照组相比差异有统计学意义（P＜0.05）；接种经浓度为0.2μg/ml、0.5μg/ml两性霉素B破坏脂筏的菌悬液后，其致死率和感染率亦有不同程度的降低，但与对照组相比差异无统计学意义（P＞0.05）。感染小鼠的各脏器组织病理改变主要为急性化脓性炎症及肉芽肿性炎症，组织中可见关节孢子和菌丝。结论 T. asahii脂筏形成受到两性霉素B抑制后，其致死率和感染率明显降低，并随着药物浓度的增加而梯度减弱，即致病性相应降低。提示脂筏有可能成为抗真菌药物研究的新的靶位。