摘要
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 in the progression of liver fibrosis in mice infected with Clonorchis sinensis.Methods C3H/HeN(TLR4 wild type) and C3H/HeJ(TLR4 mutation) mouse model infected with Clonorchis sinensis were used in this study.Livers were removed from mice at various time after infection(1d,7d,2W,4W,8W,12W).Pathological changes of HE and Masson staining in the liver were observed.Results The liver pathological changes in C3H/HeN could begin to be observed at 2W,lesions gradually increased with prolongation of infection,which could be observed in C3H/HeJ at 2W,and more serious at 4W,and decreased significantly at 8W.HE and Masson staining of C3H/HeN prolonged with infection time,the degree of liver fibrosis aggravated gradually,and began to be stable at 8W.The fibrosis score from 2W to 12W was higher than that before infection(P 0.01),while C3H/HeJ could be observed at 2W,and reached the peak at 4W(P0.01),decrease significantly at 8W.Comparing with C3H/HeN,the degree of liver fibrosis of C3H/HeJ were reduced significantly at 2W,4W,8W,12W(P0.01).Eosinophil of HE staining could be observed after 7day infection,reached the peak at 4W and decreased significantly at 8W and 12W in C3H/HeN mice.Compared with C3H/HeN,the numbers of eosinophils of C3H/HeJ decreased significantly at 2W,4W,8W(P0.05).Conclusion Deletion of TLR4 in the mice may slow the progression of liver fibrosis induced by Clonorchis sinensis.
出处
《中国热带医学》
CAS
2014年第5期541-544,共4页
China Tropical Medicine
关键词
华支睾吸虫
TLR4
肝纤维化
炎症
Clonorchis sinensis
Toll-like receptor 4(TLR4)
Liver fibrosis
Inflammation