猪血清攻击后肝纤维化大鼠α-SMA、TIMP-1在肝组织内持续表达

Persistent Expression of α-SMA and TIMP-1 of Tissue Hepatic Stellate Cells in Liver Fibrogenesis Triggered by Pig Serum in Rats

目的猪血清法肝纤维化模型中,致纤维化因子停止作用于肝脏后α-SMA、TIMP-1阳性HSCs表型与组织中I型胶原表达的相关性。方法猪血清10周法制作大鼠肝纤维化模型,于造模6周、10周、14周和20周,免疫组织化学观察α-SMA、I型胶原,肝组织原位杂交法检测TIMP-1阳性表型HSCs在肝组织中的分布,计算机图像分析系统测定阳性比率,SPSS11.0分析各参数在肝纤维化进程中相关性。结果α-SMA于造模第6周、10周即有表达,主要分布于汇管区血管或中央静脉内膜下。于造模第14周、20周时持续表达。TIMP-1于造成模第6周时,表达也限于汇管区血管和中央静脉内膜下。造模第10周、14周时阳性表达率明显增加,向肝组织内伸展,并持续维持高阳性表达至造模第20周。α-SMA和TIMP-1在造模过程中随肝纤维化的进程呈显著正相关(r=0.989,P=0.000),二者分别与Ⅰ型胶原呈显著正相关(r=0.893,P=0.000;r=0.923,P=0.000)。结论猪血清攻击法肝纤维化大鼠模型中,致纤维化因子启动肝纤维化进程,但不随致纤维化因子的终止而终止。所以,抗肝纤维化治疗成为治疗本病的关键。

Objectives To explore the development of fibrosis and correlation between the expressions of coUagen type I and α-SMA, TIMP-1 positive phenotype of HSCs during and after pig serum＇s attack on model rats. Methods Preparing hepatic fibrosis rat model by 10 weeks of peritoneal injection of pig serum, and at week 6, 10 （stop point of model making）, 14 and 20 from the start of model making, we observed the distribution of α-SMA, TIMP-1 positive phenotype of HSCs by method and in situ hybridization and analyzed histological images by computerized image analysis system The correlation of hepatic fibrosis parameters was analyzed by SPSSI 1.0. Results Expression of n-SMA begins at week 6 through 10, and persists at week 14 and 20, at the points of which pig serum has stopped acting on model rats for 4 through 10 weeks respectively. It distributed mainly under the tunica iutima of veins in the area of portal sepia and porisinusoid. Expression of TIMP-1 was also observed at week 6 and limits to inner membrane of vessels, but at week 10 through 14th the expression increased significantly and invaded towards inner part of liver tissue, and persisted high expression to week 20. There was a significant correlation between α-SMA and TIMP- 1 during the course of fibrogenesis （ r = 0.989, P = 0.001 ）, both α-SMA and TIMP- 1 were significantly correlated to the expression of collagen type I （ r = 0. 893, P = 0. 001 ; r = 0.923, P = 0. 001 ）. Conclusions In heterogeneous serum model of hepatic fibrosis, the trigger factors switch on fibrogenesis eourse, but can not switch it off afterwards. This indicates anti-fibrosis treatments are the same key things to do with etiological treatments as anti-virus therapy in chronie virus hepatitis in human.