[Antifibrotic effects of cyclic RGD-peptide mediated liposomal interferon: an experimental on rats].
OBJECTIVE
To evaluate the antifibrotic effect of receptor-mediated sterical stability liposome (SSL) targeting hepatic stellate cells (HSCs) and containing recombinant human interferon-alpha 1b (IFNalpha-1b) on hepatic cirrhosis.


METHODS
The ligand, cyclo (RGD) with specific affinity to HSCs, was incorporated via PEG into the lipid bilayers of SSL. Forty male SD rats were randomly divided into 4 equal groups: liver fibrosis model group undergoing double ligation and cutting of the common bile duct (BDL group), BDL + IFN-SSL group, undergoing BDL and injection of IFN 50,000 IU per week via caudal vein for 4 times; IFN-RGD-SSL treatment group, undergoing BDL and injection of IFN-RGD-SSL (equal to 50,000 IU per week) via caudal vein for 4 times; and sham operation group used as control. The rats were killed 24 hours after the last injection. Their livers and serum samples were collected. Pathological changes of the liver were observed with HE and alpha-SMA immunohistochemical staining. Biochemical automatic analyzer was used to test the serum indices of liver function: ALT, AST, total bilirubin (TBIL), alkaline phosphatase, and gamma-glutamine (gamma-GT). Radioimmunoassay method was used to examine the s serum index of liver fibrosis: HA, procollagen III (PCIII), LN, and CIV. Colorimetry was used to examine the level of hydroxyl proline (Hyp). RT-PCR was used to detect the mRNA expression of type I collagen. Western blotting was used to examine the protein expression of alpha-SMA of HSC.


RESULTS
Compared with the control group, liver fibrosis was seen in the other 3 groups, especially in the BDL group. In comparison with the sham operation group, the levels of serum indices of liver fibrosis, liver hydroxyl proline content, and expression of type I collagen mRNA and alpha-SMA protein in liver were significantly higher in the other groups (all P < 0.05), being significantly lower in the BDL + IFN-RGD-SSL group than in the BDL + IFN-SSL group (all P < 0.05).


CONCLUSIONS
The receptor-mediated IFN-RGD-SSL displays good targeting antifibrotic effects on liver fibrosis.
Du
Shi-lin
SL
Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Wang
Ji-yao
JY
Pan
Hong
H
Lu
Wei-yue
WY
Wang
Jian
J
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D007370:Interferon Type I / Q000627:therapeutic use*; D008081:Liposomes; D008106:Liver Cirrhosis, Experimental / Q000628:therapy*; D008111:Liver Function Tests; D008297:Male; D009842:Oligopeptides / Q000627:therapeutic use*; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins
D000199:Actins; D024042:Collagen Type I; D007370:Interferon Type I; D008081:Liposomes; D009842:Oligopeptides; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D011994:Recombinant Proteins; C498862:Acta2 protein, rat; C047981:arginyl-glycyl-aspartic acid