[Regional gene delivery via the bile duct to damaged liver using peptide/DNA particles: experiment with rats].

Objective: To evaluate the efficacy of gene delivery to the right lateral lobe of liver via a branch of the bile duct.

Methods: Twenty LEW rats underwent intraperitoneal injection of D-galactosamine to establish acute liver damage models and were randomly divided into 5 groups to undergo ligation of the common bile duct and left bile duct 4, 5, 6, or 7 days after the acute liver damage. Non-viral vector gene compound, polylysine-molossin/pGL3 containing firefly luciferin gene or CMVbeta containing beta-galactosidase of Escherichia coli/fusogenic) was injected in to the right lateral lobes 2 and 3 via the branch of right bile duct. Four rats without injection of D-galactosamine but undergoing injection of polylysine-molossin/pGL3 or CMVbeta/fusogenic were used as normal controls. Twenty-four hours after the regional gene delivery the rats were killed. The expressions of luciferin and beta-galactosidase in different lobes were detected. Pathological examination of liver was conducted.

Results: All rats survived after the operation. The expression levels of luciferin in the liver on the days 4, 5, and 6 were all significantly higher than that of the normal control rats (all P < 0.05). The expression levels of luciferin in the liver on the day 7 was the highest compared with the normal control rats (P = 0.01). However, the level of luciferin in the liver on the day 9 was lower and not significantly different from that of the normal rats (P > 0.05). Scattered distribution of beta-galactosidase was seen in the lobe 2 of the rats with acute liver damage. The levels of alanine transaminase and aspartate aminotransferase were slightly increased and the albumin level was slightly decreased in the rats with acute liver damage on the days 4 and 7, however, these biochemical indexes were not significantly correlated with the gene expression. There was no obvious histological difference between the lobes 2 and 3 and lobe 1.

Conclusion: Gene delivery with peptide/DNA complexes shows a good expression in the acute damaged liver without aggravating the liver damage, thus providing a technical platform for the experimental research of liver gene therapy.