[Therapeutic Effects of Octreotide on Hepatofibrosis-induced with Carbon Tetrachloride in Rats]

Objectives: To investigate the therapeutic effects and mechanism of octreotide on experimental hepatic fibrosis in rats.

Methods: Hepatofibrotic rats models were established with carbon tetrachloride. All the experimental rats were divided into four groups: normal control group, pre-and post-treatment model group, and octreotide-treated group in which the rats were injected subcutaneously with octreotide at the dose of 50ng/100g, twice daily, for thirty days. Serum levels of hyaluronic acid (HA), laminin (LN) and pro-collagen type III peptide (PCIII) were detected by radioimmunoassay. Hepatic fibrosis scoring grade was assessed through Van-Gieson staining and observed under light microscope. Protein expression levels of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor beta1 (TGFbeta1) were determined with immunohistochemical staining method. Messenger RNA (mRNA) levels of collagen type I and PCIII were detected by reverse transcription polymerase chain reaction.

Results: Serum levels of HA (ng/L), LN (microg/L) and PCIII (ng/L) in pre- and post-treatment model groups were higher than those in normal control group (121.8+/-9.5 and 110.3+/-13.4 vs. 33.1+/-3.7, 85.7+/-12.1 and 78.2+/-7.9 vs. 37.1+/-6.3, 35.9+/-3.5 and 33.7+/-2.6 vs. 15.6+/-2.8, respectively, t > or = 9.41, P<0.05), and there was no significant difference between the two model groups. Concentrations of HA (55.8ng/L+/-7.2ng/L), LN (43.1microg/L+/-3.4microg/L) and PCIII (27.8ng/L+/-3.4ng/L) decreased significantly in octreotide-treated group, compared with those in model groups (t >or=2.76, P<0.05). With histological analysis, fibrotic scoring grade in octreotide-treated group was obviously ameliorated, compared with that in model groups (chi2 > or = 3.97, P<0.05). Imaging analysis revealed that alpha-SMA and TGFbeta1 immunohistological staining areas were markedly shrinked in octreotide-treated group (t > or = 2.47, P < 0.05). In two model groups, PCIII and type I mRNA levels significantly up-regulated as compared with those in normal group (t > or = 9.27, P<0.001), and they were inhibited by octreotide markedly (t > or = 2.47, P<0.05).

Conclusions: Octreotide can inhibit hepatic stellate cells transforming into myofibroblasts, down-regulate TGFbeta1, collagen type I and PCIII transcriptions, so that it has therapeutic effects on experimental hepatic fibrosis.