Heme Oxygenase / Carbon Monoxide System In Gestational Intrahepatic Cholestasis Of Expression And Significance

Background and objective : Heme oxygenase (HO) catalyzes the oxidation of heme to carbon monoxide ,biliverdin ,and iron .The major expression of HO-2 protein has been demonstrated in the human organ and tissue for example :liver,placenta,uterus.Many researches indicate that CO generated by heme oxygenase controls the biliary excretion and increase in excretion of bile salts and phospholipids.pregnancy elicits a marked physiology change ,these alterations influence the expression of HO and levels of endogenous CO.This study aimed to investigate whether exceptional CO levels induce disfunction of the biliary excretion while heme oxygenase is expressed unsteadily ,thus result in development of intrahepatic cholestasis .To evaluate the influence of CO on the biliary excretion and the feto-maternal circulation ,this study was to compare endogenous CO and HO-2 protein expression level in womem with intrahepatic cholestasi of pregnancy (ICP) to the levels in healthy pregnancy .we quantified endogenous CO in the maternal plasm and the plasm of umbilical blood by spectrophotometer ;immunohistochemistry was used to detect HO-2 protein expression in placenta villi third trimester .this study discuss if heme oxygenase /carbon monoxide system make the difference to our understanding of the pathogenesis of ICP and whether abnormal HO/CO system may be one of the important mechanisms for the bad outcome of fetal. Methods : 1. Content of endogenous CO in the maternal plasm and the plasm of umbilical blood were quantified with spectrophotometer. 2. Hepatic function (total bile acid , alanine aminotransference, asparatate aminotransference) 3. Immunocytocheical ananlysis was used to detect the expression of heme oxygenase protein in the placenta villi. Results: 1. Spectrophotometer analysis demonstrated that the level of endogenous CO in the maternal plasm of ICP group and control group were (33.0±10.9)umol/L and (38.3±6.1)umol/L, there were no significant difference between the ICP group and the control group (P<0.05)。. 2. The level of endogenous CO in the umbilical blood plasm of ICP group was (26.7±7.0)umol/L,significantly lower than that of the control group [(31.1±7.7)umol/L](P<0.05)。 3. There was relation with the level of CO and the value of TBA(r=-0.32,P<0.05) 4. There were no relation with the level of CO and fetal weigh , Apgar score,gestation and the value of S/D in umbilical artery . 5. The result of immunohistochemistry demonstrated that HO-2 predominantly localized in trophoblast as well as capillaries ,with weak staining of villous stroma. 6. The semi-quantitative analysis demonstrated that the ODvalue of HO-2 in the ICP group placenta was 0.88±0.41 , significantly lower than that of the control group(P<0.05) Conclusion: HO/CO system could mitigate the symptom of intrahepaticcholestasis in ICP group .The level of CO were reduced and the expression level of HO-2 proteion were decreased in ICP group .HO/CO as endogenous system may regulate feto- placenta circulation ,indicated their change correlated with the bad outcome of fetal in ICP group .