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目的探讨TLR4基因在华支睾吸虫感染小鼠致肝纤维化中的作用。方法建立感染华支睾吸虫C3H/HeN(TLR4野生型)与C3H/HeJ(TLR4基因突变型)小鼠模型,在感染后1d、7d、2W、4W、8W、12W取小鼠肝脏,切片并进行HE和Masson染色,观察病理变化。结果 C3H/HeN小鼠肝脏大体病变从2W开始,随感染时间延长而加重;C3H/HeJ小鼠从2W开始,4W加重,至8W已明显减轻。观察HE、Masson染色肝脏切片示随感染时间的延长,C3H/HeN小鼠前期肝纤维化逐渐加重,至8W起趋于稳定;2W~12W纤维化评分均高于感染前(P<0.01)。C3H/HeJ小鼠肝纤维化评分2W升高,4W达高峰并显著高于感染前(P<0.01),至8W明显下降。与C3H/HeN比较,感染后2W、4W、8W、12W C3H/HeJ小鼠肝纤维化程度轻(P<0.01)。感染后7d,C3H/HeN小鼠的HE染色切片上可见嗜酸性粒细胞,4W达高峰,此后明显减少。感染后2W、4W、8W,C3H/HeJ小鼠嗜酸性粒细胞较C3H/HeN小鼠少(P<0.05)。结论 TLR4基因缺失可能在华支睾吸虫感染致肝纤维化过程起一定的阻制作用,从而减缓肝纤维化的进程。
Objective To investigate the role of TLR4 gene in hepatic fibrosis induced by Clonorchis sinensis in mice. Methods The mouse models of C3H / HeN (Clonorchis sinensis) and C3H / HeJ (TLR4 mutant) mice infected with Clonorchis sinensis were established. The livers of mice were harvested at 1d, 7d, 2w, 4w, HE and Masson staining were performed to observe the pathological changes. Results The general pathological changes of liver in C3H / HeN mice started from 2W, and aggravated with the prolongation of infection time. The C3H / HeJ mice started from 2W and exited in 4W, and was significantly reduced to 8W. Hematoxylin and eosin (HE) and Masson stained liver slices showed that the hepatic fibrosis gradually increased in the early stage of C3H / HeN mice and stabilized at 8W. The scores of 2W ~ 12W fibrosis were higher than those before infection (P <0.01). The liver fibrosis score of C3H / HeJ mice increased 2W, reached the peak at 4W and was significantly higher than that before infection (P <0.01), and significantly decreased to 8W. Compared with C3H / HeN, the hepatic fibrosis in 2W, 4W, 8W, 12W C3H / HeJ mice after infection was light (P <0.01). Seven days after infection, eosinophils were observed on the HE staining sections of C3H / HeN mice, reaching a peak at 4W, and were significantly reduced thereafter. In 2W, 4W, 8W and C3H / HeJ mice, eosinophils were less than C3H / HeN mice (P <0.05). Conclusion The loss of TLR4 gene may play a role in inhibiting the process of hepatic fibrosis induced by Clonorchis sinensis infection and thus slow down the progression of hepatic fibrosis.