日本血吸虫抗独特型抗体NP30对急性血吸虫病的免疫治疗作用

Treatment effectiveness of anti-idiotypic antibody NP30 for acute schistsomiasis

目的探讨日本血吸虫抗独特型抗体NP30对急性血吸虫病的免疫治疗作用。方法根据L9(34)正交表设计动物实验,日本血吸虫尾蚴感染C57BL/6小鼠后注射抗独特型抗体NP30,观察不同治疗方案各组小鼠的存活时间并计算不同时间段的生存率,取小鼠肝脏石蜡切片,HE染色,测量小鼠单个虫卵肉芽肿的直径及面积。结果各实验组小鼠的生存中位数为45～78d,其中第4组生存中位数为71d,比同样感染40条尾蚴的对照组2(53d)延长了33.96%。Cox回归分析显示小鼠存活时间主要与尾蚴感染水平、抗体注射途径有关(P均<0.05)。各实验组小鼠单个虫卵肉芽肿平均直径为179.07～226.86μm,平均面积为(32.11～51.37)×103μm2;对照组各组小鼠单个虫卵肉芽肿平均直径为205.89～239.86μm,平均面积为(44.61～57.24)×103μm2。极差分析及方差分析均显示抗独特型抗体NP30的注射方式和注射剂量是影响虫卵肉芽肿平均直径和面积的主效应因素。NP30的最佳免疫治疗方案为感染尾蚴28d后,以每鼠每只20μg的剂量连续3次肌肉注射。结论抗独特型抗体NP30可改善血吸虫感染小鼠的生存状况,降低血吸虫对宿主造成的免疫病理损害,具有治疗急性血吸虫病的潜能。

AbstraObjective To study the immunotherapeutic efficacy of anti-idiotypic antibody NP30 for acute schistosomiasis japonica. Methods Animal tests were designed according to orthogonal table L9 （ 34 ）. C57BL/6 mice were infected with Schistosoma japonicum cercariae followed by injection of anti-idiotypic antibody NP30. The survival time of each mouse was observed and survival rates of each group in different periods were calculated. Paraffin sections and HE staining of liver tissue of each mouse were carried out to analyze the average diameters and areas of all granulomas surrounding single egg. Results The median survival time of each experimental group ranged from 45 days to 78 days. Among them, the group 4 was 33.96% longer than that of the control group 2 （71 days versus 53 days）. Cox regression analysis showed that the survival time was mainly related with the levels of infected cercariae and injection route of NP30 （P〈0.05 ）. The average diameters of the experimental groups were 179.07- 226.86μm while the average areas were ranged from 31.11×10^3μm^2 to 51.37 ×10^3 μm2. And the average diameters of control groups were 205.89-239.86μm with the average areas of granuloma ranged from 44.61 ×103μm^2 to 57.24 × 103μm^2. The range analysis and variance analysis showed that the effect of injection ways and dosages of NP30 on average diameters and areas of egg granuloma were predominant. The optimal therapeutic schedule was that NP30 should be injected through muscles continuously 3 times with dosage of 20 μg each time 28 days after infection. Conclusion The injection of NP30 could improve the survival situation of infected mice and reduce immunopathologic damage caused by Schistosoma japonicum, and NP30 seems to have the potency for treatment of acute schistosomiasis japonica.