The Effect of Lecithins Coupled Decorin Nanoliposomes on Treatment of Carbon Tetrachloride-Induced Liver Fibrosis

الملخص EN

This study aimed to investigate the effect of bile duct-targeting lecithins- (PC-) coupled decorin (DCN) (PC-DCN) nanoliposomes against liver fibrosis in vitro and in vivo.

We prepared PC-DCN nanoliposomes by using rat astrocytes, HSC-T6, to verify the antifibrosis effect of PC-DCN in vitro.

First, we established a rat model of carbon tetrachloride-induced fibrosis.

PC-DCN nanoliposomes were then injected into fibrotic rats via the portal vein or bile duct.

The EdU assay was performed to analyze cell proliferation.

Immunofluorescence staining was used to detect α-smooth muscle actin (α-SMA) expression.

Western blot was performed to examine the expression of α-SMA, collagen type I alpha 1 (COL1A1), and transforming growth factor-β (TGF-β) protein.

The levels of aspartate transaminase (AST), alanine transaminase (ALT), and total bilirubin (TBIL) were examined by enzyme-linked immunosorbent assay (ELISA) analysis.

Hematoxylin and eosin (H&E) staining and Masson trichrome staining were used to determine liver tissue lesions and liver fibrosis.

Compared with TGF-β group, PC-DCN treatment could significantly reduce cell proliferation.

Western blot analysis indicated that the expression of α-SMA, COL1A1, and TGF-β was downregulated after treatment with PC-DCN in vitro and in vivo.

Immunofluorescence staining confirmed that α-SMA expression was reduced by PC-DCN.

Furthermore, H&E staining and Masson trichrome staining showed that the administration of PC-DCN nanoliposomes via the bile duct could reduce the extent of liver fibrosis.

PCR analysis showed that PC-DCN administration could reduce proinflammatory cytokines IL-6, TNF-α, and IL-1β expression via the bile duct.

The administration of PC-DCN nanoliposomes also significantly downregulated liver function indicators ALT, AST, and TBIL.

The results of our study indicated that PC-DCN could effectively reduce the extent of liver fibrosis.