Ⅱ型弓形虫和血吸虫重叠感染对小鼠肝纤维化作用的实验研究

Experimental study on the effects of Toxoplasma gondii and Schistosoma japonicum overlapping infection on the liver fibrosis in mice

目的观察Ⅱ型弓形虫和日本血吸虫重叠感染对小鼠肝纤维化的影响,探讨弓形虫感染诱导的抗感染免疫对血吸虫感染致小鼠肝脏纤维化的免疫调节作用。方法BALB/c小鼠建立重叠感染模型:预先感染血吸虫(模型Ⅰ组);预先感染PRU株弓形虫(模型Ⅱ组);对照:只感染尾蚴组和正常对照组。取上述小鼠血液及肝脏,HE和Masson胶原纤维染色法观察肝脏虫卵肉芽肿大小和肝纤维化面积;检测纤维化指标透明质酸(HA)和肝脏羟脯氨酸(HYP)含量。结果模型Ⅰ组小鼠肝脏病理及纤维化指标检测与相应对照组未见显著差异;模型Ⅱ组动物血清HA和肝脏HYP显著低于相应对照组(P<0.001),肝脏虫卵肉芽肿大小和纤维化面积均显著减小(P<0.001)。结论预先感染Ⅱ型弓形虫可能诱导机体的Th1型应答的偏移,在此微环境下可负向调控血吸虫肝脏纤维化状态的Th2应答,从而延缓和减弱肝纤维化的发生和发展。

Objective To explore the positive effect of overlapping infection of Toxoplasma gondii and Schistosomiasis japonica on the hepatic fibrosis of mice. Methods BALB/c mice （specific pathogen free） were transcuta- neously infected with （15 ±2） larvae of Schistosoma japonicum to generate a model of chronic infection after 42- 56 days of larval infection, followed by an intragastric infection of 10 cysts Toxoplasma gondii PRU strain （ group I）. Simultaneously, mice received 10 cysts infection of Toxoplasma gondii to establish a chronic infection with 35 days, followed by （15 ± 2） larvae infection of Schistosomajaponicum （group 11 ）. Equal number of normal animals were taken as control. Blood and liver tissue samples were collected for HE and Masson staining respectively. The size of liver egg granulomas and fibrosis areas were measured. Additionally, hyaluronic acid （HA） and hydroxyproline （HYP） in sera were tested. Results Pre-infection of PRU strain of Toxoplasma before Schistosoma japonicum infection resulted in a remarkable amelioration of hepatic fibrosis in mice, presenting the reduced size of egg granulomas and tissue fibrosis （ P 〈 0. 001 ）. And HA and HYP levels were significantly decreased in the mice with Toxoplasma pre-infection （ P 〈 0. 001 ）. In contrast, the established chronic infection of schistosomiasis of mice, followed by oral reinfection with 10 cysts of Toxoplasma, did not show any inhibitory effects on hepatic fibrotic procession. Conclusion Pre-establishment of Thl immune response induced by Toxoplasma may help the animals which were infected with Schistosoma japonicum to ameliorate the procession of hepatic fibrosis.