刚地弓形虫感染致Th1／Th2细胞因子变化对大鼠生精细胞的影响

Effect of Th1/Th2 cytokines fluctuation on spermatogenic cells caused by Toxoplasma gondii infection

目的研究弓形虫感染后雄性大鼠Th1、Th2细胞因子IFN-γ、IL-4及一氧化氮（NO）水平的变化，探讨其对雄性睾丸生精细胞损伤的影响。方法选用9～10周龄雄性SD大鼠132只，按随机数字表法分为3组：正常对照组、低剂量感染组（1×10。个速殖子）、高剂量感染组（1×10^4个速殖子），感染后第0、3、6、9、……30天，感染组和对照组分别取4只大鼠，检测大鼠血清IFN-γ、IL-4及NO的水平，并且做睾丸的病理学检查和精子计数。结果弓形虫感染组大鼠血清IFN-γ显著升高，低剂量组及高剂量组在第6天达峰值，分别为（286．3±45．3）pg/ml和（506．6±34．3）pg／ml；血清NO亦显著升高，高剂量组第9天达峰值（77．7±7．0）μmol/L，低剂量组第12天达峰值（59．5±5．3）μmol／L，之后均迅速降低；感染组大鼠血清IL4逐渐升高，低剂量组及高剂量组于第15天达峰值（233．3±36．9）pg/ml、（366．7±52．4）pg/ml后逐渐降低。以上指标至实验末期均未恢复正常水平。病理检查显示，正常对照组大鼠生精小管层次清晰，细胞丰富，精子计数为175．7±23．7，感染组大鼠生精小管层次混乱，精母细胞、精子细胞明显减少，低剂量组及高剂量组至第15天达谷值84．5±23．5、47．3±14．7，至实验末期无明显恢复。结论弓形虫感染导致的早期Th1细胞因子IFN-γ极化及NO显著升高，随后引起Th2细胞因子IL4反应性增高，并介导以精母细胞为主的生精细胞损伤及生精障碍。

Objective To study the effect of fluctuation of Thl, Th2 cytokines IFN-~/,IL-4 and nitric oxide on spermatogenie cells in male rats after Toxoplasma infection. Methods 132 male SD-rats（9-10 week） were randomly divided into three groups： negative control group, low dose infection group（ 1 × 10^2 tachyzoites） and high dose infection group （1 × 10^4 tachyzoites ）. Four rats of control group and infection groups were excuted on the 0,3,6,9... and 30 day after infection, then the levels of serum IFN-γ, IL-4, NO were detected, the pathology of spermatogenic cells examined and sperms counted. Results IFN-γ in serum increased significantly in infection groups, low dose infection group and high dose infection group reaching the peak on 6 d, respectively （286.3 ± 45.3 ） pg/ml and （506.6 ± 34.3 ） pg/ml ; NO in serum increased significantly too, high dose group on 9 d（77.7 ± 7.0）μmol/L while low dose group got to peak on 12 d （59.5 ±5.3 ） μmol/L, then both decreased rapidly. IL-4 in serum of infection groups rats increased gradully, low dose group（233.3 ± 36.9） pg/ml and high dose group（366.7 -52. 4） pg/ml reaching the peak on 15 d and then deceased. However, the levels of above cytokines did not return to normal till the termination of experiment. Pathological examination showed clear seminiferous tubules layers and rich cells in normal control group rats with sperm counted 175.7 ± 23. 7, while in infection group rats＇ seminiferous tubules layers were in disorder and spermatocytes, spermatids reduced significantly, which counted as low dose group （ 84.5 ± 23.5 ） and high dose group （47.3 ± 14.7） to valley value on 15 d. Those changes did not recover at the end of the experiment. Conclusion Toxoplasma gondii infection led to Thl cytokines IFN-γ polarization and NO increasing in early stage, followed by Th2 cytokine IL-4 increasing reactively. As a result, spermatogenic cells mainly spermatocytes weredamaged and spermatogenesis impaired.