The Interference And Therapy Of CGRP And The Receptor Antagonist To Hepatic Microcirculation In Acute Injury

AIM Interview the change of content of CGRP in acute hepatic injury induced by concanavalin A(Con A) to investigate the role of CGRP in this hepatitis model. Meanwhile,by inject CGRP and the CGRP receptor antagonists CGRPg-37 via the tail vein at different concentrations and times,We sought to reveal the interference and therapy of CGRP to hepatic microcirculation in acute hepatic injury induced by ConA and to provide the experimental basis for the clinical treatment or reversion of liver injury.Methods (1)10 Kun-Ming rats were injected with ConA 20mg/kg via the tail vein to set up the model, Other 10 rats were injected with saline to compare, the changes of content of CGRP in liver homogenates were detected by radioimmunoassay (RIA).(2)120 Kun-Ming rats were divided into six groups randomly, acute hepatic injury group was established by injection with 20mg/kg Con A through the tail vein. The saline control group was established by injection with saline. In CGRP-administered group 1 CGRP was given to rats 30min before ConA. In CGRP-administered group 2 CGRP were injected as soon as ConA.In the CGRP-therapy-group 1 and 2,CGRP was given after 2 hours or 4 hours when ConA injection.(3) 120 Kun-Ming rats were divided into six groups randomly, harvested rat livers were perfused via the portal vein with 2mL of CGRP solution at different concentrations (50ug/kg,200ug/kg,400ug/kg) inⅠ,ⅡandⅢgroup; pretreating mice with various doses of the CGRP receptor antagonists CGRP8-37 (50mol/kg,100mol/kg,200mol/kg) inⅣ,ⅤandⅥgroup.(4)Ten mice in each group were used to observe the average liver blood flow volume and concentration by laser-Doppler flow instrument, and the other ten rats were observed the hepatic microcirculation velocity in vivo by an inverted microscope. Liver damage was assessed by histological evaluation.Results (1) CGRP contents in liver homogenates were significantly increased in injury group,which was obviously higher than those in control group (P＜0.01); (2) The average liver blood flow volume and the hepatic microcirculation velocity were decreased after ConA injection, which in pretreatment group increased remarkably comparing with the injury group (P<0.01); Compared with the injury group, the detection datas in the CGRP-therapy-group 1 were increased remarkably just as the pretreatment group; the change of average blood flow volume and the flow velocity in the CGRP-therapy-group 2 were less than that in the pretreatment group and CGRP-therapy-group 1 group (P<0.01), while which were almost the same as injury group(P>0.05); the concentration in each group were almost the same (P>0.05).(3) The CGRP concentration-dependently caused a significant increase in the average liver blood flow volume and velocity; by pretreating mice with various doses of the CGRP receptor antagonists CGRP8-37, tendency to aggravated liver damage by high doses of the receptor antagonists was detectable.(4) There are edema formation, hepatocellular apoptosis and granulocyte infiltration in livers of injury group, and these signs were reduced significantly in the pretreatment group and theCGRP-therapy-groupl whereas these didn't happen in the CGRP-therapy-group 2.Conclusions (1) contents of CGRP in liver homogenates in injury group were obviously higher than those in control group, which suggest that CGRP may play an important role in this hepatitis model.(2) Using CGRP can decrease the dysfunction of hepatic microcirculation by means of improving the tissue perfusion, and alleviate thepathological damage during acute liver injury,which are connected with the time. So CGRP had certain therapeutic effect on liver inflammation.(3) The CGRP concentration-dependently caused a significant increase in the average liver blood flow volume and velocity; by pretreating mice with various doses of the CGRP receptor antagonists CGRP8-37, tendency to aggravated liver damage by high doses of the receptor antagonists was detectable.