Effects of hepatotrophic factors on the liver after portacaval shunt in rats with portal hypertension.
BACKGROUND
Portacaval shunt (PCS) prevent hepatotrophic factors from flowing into the liver, but they enter directly the systemic circulation and worsen liver injury. This study was designed to investigate the effects of hepatotrophic factors through the portal vein on the liver in rats with portal hypertension after portacaval shunt.


METHODS
Intrahepatic portal hypertension (IHPH) was induced by intragastric administration of carbon tetrachloride, and end-to-side PCS was performed. Eight normal rats served as controls, and eight rats with IHPH served as IHPH model (IHPH group). Another 32 rats with IHPH-PCS were randomly subdivided into 4 groups: normal saline (NS) given to 8 rats, hepatocyte growth factor (HGF) 8, insulin (INS) 8, hepatocyte growth factor and insulin (HGF + INS) 8. Hepatotrophic factors were infused into the portal vein through an intravenous catheter. Portal venous pressure (PVP) was measured. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested biochemically and those of hyaluronic acid (HA) and laminin (LN) were measured by radioimmunoassay. Hepatic fibrosis was assessed histologically and the expression of collagens type I and III were detected immunohistochemically. Ultrastructural change of hepatocytes and the number of mitochondria were observed under an electron microscope. The data were compared between groups and subgroups by Student-Newman-Keuls procedure with SPSS10.0.


RESULTS
PVP was significantly higher in the IHPH rats than in the control rats (P < 0.05). The levels of serum ALT, AST, HA, and LN, hepatic fibrosis score, the amount of collagen deposition, collagens type I and III increased more significantly in the IHPH group than in the control rats (P < 0.05). The number of mitochondria decreased more significantly in the IHPH rats than in the control rats (P < 0.05). The levels of serum ALT, AST, HA and LN as well as hepatic fibrosis score, the amount of collagen deposition, and the amount of collagens type I and III in the HGF and HGF + INS rats were significantly lower than those in the NS rats (P < 0.05). The damage to hepatocyte ultrastructure was markedly alleviated and the number of mitochondria was increased more significantly in the HGF and HGF + INS rats than in the NS rats under an electron microscope.


CONCLUSIONS
Perfusion of exogenous hepatotrophic factors through the portal vein can alleviate liver injury, minimize the damage to the ultrastructure of hepatocyte, protect liver function, and lessen hepatic fibrosis in rats with portal hypertension after PCS.
Zhang
Zhong-tao
ZT
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. zhangzht@medmail.com.cn
Jiang
Peng
P
Wang
Yu
Y
Li
Jian-She
JS
Xue
Jian-guo
JG
Zhou
Yan-zhong
YZ
Yuan
Zhu
Z
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D005109:Extracellular Matrix / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006975:Hypertension, Portal / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy; D008297:Male; D011167:Portacaval Shunt, Surgical; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D017228:Hepatocyte Growth Factor; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase