Inhibitory effects of prostaglandin E1 on activation of hepatic stellate cells in rabbits with schistosomiasis.
BACKGROUND
Liver fibrosis is the result of an imbalance between synthesis and degradation of extracellular matrix proteins of the liver. At the cellular and molecular levels, this progressive process is mainly characterized by activation of hepatic stellate cells (HSCs). Schistosoma japonica is one of the most prevalent causes of liver fibrosis in China. It is characterized by hepatocyte damage, inflammation, and chronic parasite egg-induced granuloma formation leading to fibrosis. This study aimed to investigate the inhibitory effects of prostaglandin E1 (PGE1) on activation of HSCs and the alteration of type I and III collagen in rabbits with schistosomiasis. The study may promote the clinical application of praziquantel and PGE1 as a combined therapy to reverse hepatic fibrosis caused by schistosomiasis.


METHODS
Rabbits were percutaneously infected with cercaria of S. japonicum. Seven rabbits were subjected to intravenous injections of PGE1 (2.5 mug/kg daily) from days 60 to 120 after infection. The ultrastructural changes in activated HSCs were observed under transmission electron microscopy. The expression of alpha-smooth muscle actin (alpha-SMA) was detected by immunohistochemistry. Fibril-forming collagens were detected by picrosirius staining.


RESULTS
Activation of HSCs was a characteristic alteration in schistosome-induced hepatic fibrosis. The expression of contraction-related alpha-SMA and the content of collagens were increased. Exogenous PGE1 markedly inhibited the activation of HSCs and reduced the expression of alpha-SMA around the hepatic sinusoids (P<0.01). The contents of type I and III collagens were significantly attenuated. The ratio of staining area to the whole field (10X3.3) under a polarized light microscope in the untreated and treated groups was 37.25+/-9.71 vs. 13.38+/-4.24 (P<0.01) and 9.66+/-3.52 vs. 6.23+/-1.81 (P<0.05), respectively.


CONCLUSIONS
Activation of HSCs may play a key role in the progress of schistosome-induced hepatic fibrosis. PGE1 effectively protects rabbit liver from fibrosis, at least in part by inhibiting the activation of HSCs.
Zou
Wei-Long
WL
Institute of Transplantation, General Hospital of the Chinese People's Armed Police Forces, Beijing, China. wlzouah@sina.com
Yang
Zhen
Z
Zang
Yun-Jin
YJ
Li
Dong-Jian
DJ
Liang
Zhi-Peng
ZP
Shen
Zhong-Yang
ZY
D000199:Actins / Q000378:metabolism; D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology*; D008103:Liver Cirrhosis / Q000503:physiopathology* / Q000517:prevention & control; D008297:Male; D011817:Rabbits; D012552:Schistosomiasis / Q000150:complications; D014665:Vasodilator Agents / Q000494:pharmacology*
D000199:Actins; D024042:Collagen Type I; D024061:Collagen Type III; D014665:Vasodilator Agents; D000527:Alprostadil