[Effect of sustained-release basic fibroblast growth factor on healing of bile duct defect in pigs]

To investigate the effects of sustained-release basic fibroblast growth factor (bFGF) on healing of bile duct defect.

A model of bile duct wall defect (2 cm in length and 1/3-2/3 of the bile duct circumference in width) was made in 24 pigs (male or female, weighing 15-30 kg), and then defect was repaired with sustained-release bFGF collagen membrane (2.0 cm x 1.0 cm x 0.5 cm in size) in the experimental group (n=12) or with collagen membrane (2.0 cm x 1.0 cm x 0.5 cm in size) alone in the blank control group (n=12). Another 4 healthy pigs were used to obtain normal bile duct as normal control group. The survival condition of pigs was observed after operation; at 1, 2, and 3 months after operation, the blood sampling was collected to test the changes of liver function, and the bile duct specimens were harvested to count the microvessel density (MVD) and submucosal gland by HE staining and immunohistochemistry staining; and at 3 months after operation, cholangiography examination was done.

All the animals survived to completion of the experiment. Intra-abdominal adhesion was serious in the experimental and blank control groups at 1 week after operation, but the adhesion was markedly improved in the experimental group when compared with the blank control group with time passing. The liver function test showed that alkaline phosphatase in the experimental group was significantly lower than that in the blank control group at 2 and 3 months (P < 0.05), but no significant difference in aspartate aminortransferase, total bilirubin, and albumin was found among 3 groups (P > 0.05). The histology and immunohistochemistry staining observations showed that the regeneration rates of submucosal glands and epithelium in the experimental group were faster than those in the blank control group; defect was covered with the epithelium at 2 months, and the structure was similar to that of normal control group at 3 months; and the edema and inflammation infiltration were reduced when compared with the blank control group. The counts of MVD and submucosal gland were significantly higher than those in blank control group and normal control group at 1 month after operation (P < 0.05), and then decreased and remained at normal levels at 2 months after operation. There was a positive correlation between submucosal gland counting and MVD counting in 3 groups after operation (P < 0.01). The cholangiography examination showed no biliary dilatation or cholelithiasis after 3 months in experimental group and blank control group.

Sustained-release bFGF can promote healing of bile duct defect by accelerating the vascularization, gland regeneration, and epithelialization.