[Acting mechanism of Cordyceps mycelia extract for antagonizing hepatic sinusoidal capillarization in rats with dimethylnitrosamine induced liver cirrhosis].
OBJECTIVE
To study the acting mechanism of Cordyceps mycelia extract (CME) for antagonizing hepatic sinusoidal capillarization (HSC) in rats with dimethylnitrosamine (DMN) induced liver cirrhosis.


METHODS
Rat liver cirrhosis model was established by peritoneal injection of DMN 10 mg/kg 3 times a week for 4 weeks. To rats in the CME-prevented group CME were administrated at a dose of 10 mL/kg, once a day, for 4 weeks. The observation time points were scheduled on the 3rd day (d3), and at the end of the 2nd (W2) and 4th week (W4) after modeling, and the following items were observed: hepatic ultrastructure was observed under electron microscope; expressions of CD44, von Willebrand factor (vWF) and type IV collagen (Col lV) in the liver sinusoidal walls by immunohistochemistry; matrix metalloproteinase-2 and-9 (MMP-2, MMP-9) activity under zymogram method; and serum hyaluronic acid (HA) content by radioimmunoassay.


RESULTS
Observation at d3 showed MMP-2 and MMP-9 activity significantly increased, Col IV deposition and CD44 positive staining decreased, vWF positive staining increased in the liver sinusoidal walls, the fenestrae in the sinusoidal endothelial cells (SECs) decreased, and serum HA content increased (P<0.05); at W4, SECs defenestration and sub-SECs basal membrane formation were shown. In the CME-prevented group MMP-2 and MMP-9 activity significantly decreased (P<0.05); defenestration and basal membrane formation alleviated in the early stage (d3, W4); and at W2 and W4 decreases of HA content and vWF positive staining were shown, with increase of CD44 positive staining (P<0.05), more SECs fenestrae, and alleviated basal membrane formation.


CONCLUSIONS
The elevation of MMP-2 and MMP-9 activity in the early stage, which degrades the Col IV normally distributed under the sinusoidal endothelium, is an important factor for HSC formation. CME could inhibit the initiation of HSC by decreasing MMP-2 and MMP-9 activity in the early stage, and prevent its formation by decreasing SECs injury and phenotypic changes.
Wang
Xian-Bo
XB
Shu-guang Hospital affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai.
Liu
Ping
P
Tang
Zhi-Peng
ZP
D000818:Animals; D002196:Capillaries / Q000473:pathology; D032661:Cordyceps; D004128:Dimethylnitrosamine / Q000009:adverse effects; D006503:Hepatic Veins / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000098:blood supply; D008106:Liver Cirrhosis, Experimental / Q000473:pathology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D025282:Mycelium; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004128:Dimethylnitrosamine