Octriotide Promotes PTP1B Expression To Protect Carbon Tetrachloride-induced Hepatic Fibrogenesis Rats

Objective To investigated the mechanisms of octriotide(OCT) protecting carbon tetrachloride-induced hepatic fibrogenesis rats and the effects of protein tyrosine phosphatase 1B(PTP1B) on leptin and JAK2/STAT3 signaling.Methods Adult male SD rats were divided into three groups: control, OCT and model group. The liver fibrosis models were induced with Carbon Tetrachloride(CCl4) and 5%alcohol.OCT group rats were induced by a subcutaneous injection of the same CCl4 mixture solution and octreotide(100ng/100 g twice a day). All rat were housed for 8weeks.The levels of total bilirubin(TBIL), alanine aminotransferase(ALT), aspartate aminotransferase(AST), serum albumin(ALB) and leptin in serum and Hyp in liver were tested and histopathology changes were observed. Leptin and obese receptor(Ob-Rb)expressions were observed by immunohistochemical staining. The expressions of the phosphorylation of Janus kinase2(JAK2), signal transducers and activators of transcription3(STAT3) and PTP1 B were tested by western blot.Results1.Serum test In model and OCT group, compared with control group, the levels of TBIL,ALT, AST and leptin in serum increased and serum ALB decreased(P<0.05). Compared with OCT group, in model group, the levels of TBIL, ALT, AST and leptin in serum increased(p<0.05).2.Immunohistochemistry Immunohistochemistryshowed that leptin and Ob-Rb mainly distributed in liver HSCs of CCl4-induced rats, Especially in hepatic sinus and portal area,and rarely expressed in control group rats. Octreotide significantly attenuated CCl4-induced hepatic leptin and Ob-Rb expression(p<0.05).Pathological change The liver of control group had a smooth surface without nodules and the spleen is healthy. The hepatocytes and other tissues is normal.In model group, The boundaries of liver were blurry with a lots of nodulesthe and spleen was swelling obviously.In HE staining, inflammatory cells infiltration and necrotic cels were observed.The hepatocytes destruction was not organized and normal hepatic lobules were replaced by pseudolobul. After treated with OCT, less dropsy than that in model group, and much less serious spleen was observed. HE staining demonstrated inflammatory cells and pseudolobuli were remitted.Western blot(1)Expression of Hyp in control group was higher than OCT and model group(p<0.05).Compared with OCT group, in model group, the levels of Hyp in liver increased(p<0.05)(2)The level of PTP1 B were significantly decreased in liver of only CCl4-treated rats(p<0.05). Octreotide significantly enhanced PTP1 B expression compared with model group(p<0.05). Expression of p-JAK2 and p-STAT3 were significantly increased in model and OCT group(p<0.001). Octreotide attenuated JAK2/STAT3 phosphorylation of CCl4-induced hepatic fibrosis(p<0.05).Conclusion1.OCT can ease the CCl4-induced hepatic injury and relieve liver fibrosis.2.OCT dampens leptin signaling by stimulating PTP1 B expression, which is a negative regulator of JAK2/STAT3, and thus inhibits liver fibrosis.