Dynamic Change Of Insulin-like Growth Factor-ⅠReceptors(IGF-IR) And Insulin-like Growth Factor Binding Protein-2(IGFBP-2) In Rat Liver Fibrosis

Objective:we have established the experimental liver fibrosis by injecting CCl4into rats, in order to research the dynamic changes of insulin-like growth factor-I receptors(IGF-IR) and insulin-like growth factor binding protein-2(IGFBP-2). And to make clear the association between IGF-IR、IGFBP-2and liver fibrosis, so as to provide the new train of thought and experimental guide for clinical treatment to liver fibrosis.Methods:we have distributed36Wistar rats into two groups:a normal control group(n=6) and a model group (n=30). Injecting40%CCl4into rats of model group by subcutaneous method twice a week, lasting eight weeks.The dosage of CCl4is5ml/kg firstly, and changing the dosage of CCl4into2ml/kg secondly. We adjusted the dosage of CCl4in accordance with the rats’ weight, and every week weigh one time, while the rats in normal control group were subcutaneously injected with the same dosage of oil and kill them at the end of8weeks.All rats were given the same water and common feed. At the same time and same condition,we killed equal quantity rats of the model group at the end of the2,4,6and8weeks(six rats each batch). We used the methods of hematoxylin-eosin (HE) and Masson trichrome staining to dye rats’ liver tissue pathological section.We have examined ALT and portal vein pressure of all rats.We used enzyme-linked immunosorbent assay (ELASA) to determine IGFBP-2in serum,the correlation between the IGFBP-2and the degree of liver fibrosis were analyzed.IGF-IR and IGFBP-2was assessed by immunohistochemical staining,then it was quantitated by picture-analyzed systems. The correlations among the IGF-IR、IGFBP-2、the degree of liver fibrosis and the portal pressure were analyzed.Results:(1) Under the light microscope we have observed the rats’ liver tissue pathological section which showed that the degree of hepatic fibrosis have much aggravated along with the molding time lasting in rats of the model group, while the degree of hepatic fibrosis have no changes in rats of the normal control group.(2)Compared with the normal control group, the level of serum ALT in rats of the model group showed a gradual upward trend,and there are significant difference (P<0.05or P<0.01).(3) The ELASA showed that at Week2、Week4、 Week6and Week8, the portal vein pressure mean±SD are8.43±0.86、12.26±1.31、15.03±2.29、6.22±2.08, which are much higher than in normal control group (4.65±0.55)(P<0.05or P<0.01).(4)The IGFBP-2level was significantly higher in model group than in normal group(P<0.01).The level of IGFBP was positively correlated with liverfibrosis degree (r=0.985,P<0.001).(5) Mainly Hepatic stellate cell and Kupffer cell express IGF-IR in model group, while in normal control group, the rats’ liver have very few cells expressed IGF-IR. The IGFBP-2expression was found mainly in Hepatic cytoplasmic and cell menbrane. In model gro-up, the IGF-IR and IGFBP-2expression were obviously higher than in normal group, and its were positively correlated with liver fibrosis degree and the portal pressure.Conclusion:The rats’ liver fibrosis developed along with the rise expression of the IGF-IR and IGFBP-2,which suggest that the two factors participate in the formation of liver fibrosis.