Morphological and serum hyaluronic acid, laminin and type IV collagen changes in dimethylnitrosamine-induced hepatic fibrosis of rats.
OBJECTIVE
To study the morphological and serum hyaluronic acid (HA), laminin (LN), and type IV collagen changes in hepatic fibrosis of rats induced by dimethylnitrosamine (DMN).


METHODS
The rat model of liver fibrosis was induced by DMN. Serum HA, type IV collagen, and LN were measured by ELISA. The liver/weight index and morphological changes were examined under electron microscope on d 7, 14, 21, and 28 by immunohistochemical alpha smooth muscle actin alpha-SMA staining as well as Sirius-red and HE staining.


RESULTS
The levels of serum HA, type IV collagen and LN significantly increased from d 7 to d 28 (P = 0.043). The liver/weight index increased on d 7 and decreased on d 28. In the model group, the rat liver stained with HE and Sirius-red showed evident hemorrhage and necrosis in the central vein of hepatic 10 lobules on d 7. Thin fibrotic septa were formed joining central areas of the liver on d 14. The number of alpha-SMA positive cells was markedly increased in the model group. Transitional hepatic stellate cells were observed under electron microscope. All rats in the model group showed micronodular fibrosis in the hepatic parenchyma and a network of alpha-SMA positive cells. Typical myofibroblasts were embedded in the core of a fibrous septum. Compared to the control group, the area-density percentage of collagen fibrosis and pathologic grading were significantly different in the model group (P<0.05) on different d (7, 14, and 28). The area-density percentage of collagen fibrosis in hepatic tissue had a positive correlation with the levels of serum HA, LN, and type IV collagen.


CONCLUSIONS
The morphological and serum HA, type IV collagen, and LN are changed in DMN-induced liver fibrosis in rats.
Li
Chun-Hui
CH
Department of Pathology, Affiliated Hospital of Yanbian University College of Medicine, Yanji 133000, Jilin Province, China.
Piao
Dong-Ming
DM
Xu
Wen-Xie
WX
Yin
Zheng-Ri
ZR
Jin
Jing-Shun
JS
Shen
Zhe-Shi
ZS
D000199:Actins / Q000032:analysis; D000818:Animals; D024141:Collagen Type IV / Q000097:blood*; D004128:Dimethylnitrosamine / Q000633:toxicity*; D006820:Hyaluronic Acid / Q000097:blood*; D007797:Laminin / Q000097:blood*; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000199:Actins; D024141:Collagen Type IV; D007797:Laminin; D006820:Hyaluronic Acid; D004128:Dimethylnitrosamine