[Therapeutic effects of octreotide on hepatofibrosis-induced with carbon tetrachloride in rats].
OBJECTIVE
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.
Wang
Zhi-rong
ZR
Department of Gastroenterology, Tongji Hospital, Tongji University, Shanghai 200065, China.
Li
Ding-guo
DG
Chen
Xi-mei
XM
Huang
Xin
X
Wei
Hong-shan
HS
Wang
Yu-qin
YQ
Xu
Qin-fang
QF
Lu
Han-ming
HM
D000199:Actins / Q000032:analysis; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D006820:Hyaluronic Acid / Q000097:blood; D007797:Laminin / Q000097:blood; D008099:Liver / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D015282:Octreotide / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000032:analysis; D053773:Transforming Growth Factor beta1
D000199:Actins; D024042:Collagen Type I; D024061:Collagen Type III; D007797:Laminin; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D006820:Hyaluronic Acid; D002251:Carbon Tetrachloride; D015282:Octreotide