CAJ | 학술논문

目的了解日本血吸虫感染小鼠体内Th1/Th2反应动态变化，评价Th细胞反应与肉芽肿病理改变之间的相关性。方法C57BL/6小鼠感染日本血吸虫后4、6、8、12周，分别检测其血清中IFN-γ、IL-4、IL-13水平，脾细胞中Th1/Th2比例，观察感染小鼠肝脏虫卵肉芽肿的形成和发展趋势，并评价各个细胞因子与虫卵肉芽肿大小之间的相关性。统计分析采用非参数秩和检验和Spearman秩相关分析。结果日本血吸虫感染后第4周，小鼠血清IFN-γ浓度为(2.835±0.049) 1gpg/mL，显著高于对照组的(1.787±0.174) lgpg/mL(Z=-2.646，P= 0.008)；第6周起，小鼠血清IFN-γ浓度开始逐渐降低，但直至感染12周时仍显著高于对照组(Z=-2.457,P=0.014)。血清中IL-4（Z=-2.646，P= 0.008）和IL-13（Z=-2.646，P=0.008）水平从感染6周始升高，于第8周达高峰。经可溶性虫卵抗原(SEA)刺激后，脾脏中Th1/Th2比例于感染8周时为0.5（95％可信区间0.2～1.2），12周时为0.3（95％可信区间 0.3～0.6）,均显著低于对照组（Z=2.173，P=0.030;Z=2.551，P= 0.011）。与未经SEA刺激的脾细胞相比，经SEA刺激的脾细胞Th1/Th2比例在感染第8周（Z=2.236，P=0.025）和第12周（Z=3.130，P=0.002）均显著降低。感染6周时，小鼠肝脏中开始出现大量虫卵肉芽肿，其直径随感染进展逐渐增大。相关性分析发现，感染12周时血清IL-13水平与肝脏虫卵肉芽肿直径之间存在显著负相关（r=-0.636，P=0.048）。结论血吸虫感染早期Th1反应占优势，随着血吸虫成熟并开始产卵，Th1反应逐渐减弱，而出现Th2反应极化现象。Th2反应可能在肉芽肿纤维化过程中发挥作用。
목적 료해일본혈흡충감염소서체내Th1/Th2반응동태변화，평개Th세포반응여육아종병리개변지간적상관성。방법C57BL/6소서감염일본혈흡충후4、6、8、12주，분별검측기혈청중IFN-γ、IL-4、IL-13수평，비세포중Th1/Th2비례，관찰감염소서간장충란육아종적형성화발전추세，병평개각개세포인자여충란육아종대소지간적상관성。통계분석채용비삼수질화검험화Spearman질상관분석。결과 일본혈흡충감염후제4주，소서혈청IFN-γ농도위(2.835±0.049) 1gpg/mL，현저고우대조조적(1.787±0.174) lgpg/mL(Z=-2.646，P= 0.008)；제6주기，소서혈청IFN-γ농도개시축점강저，단직지감염12주시잉현저고우대조조(Z=-2.457,P=0.014)。혈청중IL-4（Z=-2.646，P= 0.008）화IL-13（Z=-2.646，P=0.008）수평종감염6주시승고，우제8주체고봉。경가용성충란항원(SEA)자격후，비장중Th1/Th2비례우감염8주시위0.5（95％가신구간0.2～1.2），12주시위0.3（95％가신구간 0.3～0.6）,균현저저우대조조（Z=2.173，P=0.030;Z=2.551，P= 0.011）。여미경SEA자격적비세포상비，경SEA자격적비세포Th1/Th2비례재감염제8주（Z=2.236，P=0.025）화제12주（Z=3.130，P=0.002）균현저강저。감염6주시，소서간장중개시출현대량충란육아종，기직경수감염진전축점증대。상관성분석발현，감염12주시혈청IL-13수평여간장충란육아종직경지간존재현저부상관（r=-0.636，P=0.048）。결론혈흡충감염조기Th1반응점우세，수착혈흡충성숙병개시산란，Th1반응축점감약，이출현Th2반응겁화현상。Th2반응가능재육아종섬유화과정중발휘작용。
Objective To investigate the dynamic changes of T helper (Th) responses and hepatic granuloma development during Schistosoma japonicum infection and to evaluate the possible correlation between the Th1/Th2 cytokines and pathological liver damage. Methods Sera from both Schistosoma japonicum infected C57BL/6 mice and uninfected controls were measured for interferongamma (IFN-γ), interleukin (IL)-4 and IL-13 at week 4, 6, 8 and 12 post-infection. At the same time, the splenic Th1/Th2 ratio was examined. The development of liver granulomas in infected mice was also observed and the correlation between the cytokines and granulomas were assessed. Wilcoxon test and Spearman rank correlation test were performed for data analysis. Results Serum IFN-γ level in infected mice was (2. 835±0. 049) lgpg/mL at week 4 post infection, which was significantly higher than that in controls [(1. 787 ± 0. 174) lgpg/mL, Z= - 2. 646, P = 0. 008]. Thereafter, the level declined after week 6, but remained higher than controls at the end of 12-week experiment (Z= -2.457, P=0. 014). IL-4 and IL-13 levels did not increase until week 6 (Z=-2. 646,P=0. 008;Z=-2. 646,P=0. 008), and peaked at week 8. After soluble egg antigen (SEA) stimulation, splenic Th1/Th2 ratio in infected mice was 0.5 (95％ CI 0. 2-1.2) at week 8 and 0.3 (95％ CI 0. 3-0.6)at week 12 post infection, both of which were significantly lower than those in uninfected controls (week 8: Z=2. 173, P=0.030; week 12:Z=2.551, P=0.011). Compared with unstimulated splenic cells, splenic Th1/Th2 ratio after SEA stimulation significantly decreased at week 8 (Z=2. 236, P=0. 025) and week 12 (Z=3. 130, P=0.002). Granulomas were first observed in livers at week 6 and the size kept on increasing. A negative correlation between serum IL-13 and the diameter of liver granulomas was discovered at week 12 post infection (r=0. 636, P= 0. 048). Conclusions Th1 response is dominant during the early stage of Schistosoma japonicum infection. However,followed by oviposition, Thl response declines and meanwhile a strong Th2 response gradually develops. Therefore, Th2 response probably plays a role in the development of hepatic granulomas.