The Study On Influence Of Changcd Heme Oxygenase-1in Portal Hypertension Liver Cirrhosis With Hcpatic Encephalopathy

Background: Hepatic encephalopathy (HE) is severe complication in liver cirrhosis. Atpresent, the pathogenesis of HE is still unclear and there is no effective treatment inclinical. Our previous studies show that heme oxygenase-1(HO-1) is involved in livercirrhosis and its complications, such as hepatorenal syndrome and hepatopulmonarysyndrome. However, the mechanism of HO-1in HE is still unclear.Aims: To investigate the influence of HO-1in portal hypertension liver cirrhosis withHE.Methods: Clinical test: Total of20healthy volunteers (group N),55cirrhotic patients(group C), and63patients with HE (group HE) were enrolled. Serumcarboxyhemoglobin (COHb) was measured. Animal experiment: Rats were divided intofive groups: Sham, bile duct ligation (BDL), HE induced by BDL and ammonium-containing diet, and zinc protoporphyrin (ZnPP) and cobalt protoporphyrin (CoPP)treatment groups respectively for inhibiting and inducing HO-1expression. The level ofHO-1was detected by western blot and quantitative real-time PCR (qRT-PCR).Ammonia in plasma and brain, brain water content and portal vein pressure (PVP) werealso quantified. Aquaporin-4(AQP-4) and oxidative stress response were measured byimmunohistochemistry.Results: The COHb levels were higher in group C and HE than those in group N, andwere significantly increased in HE compared to group C (p<0.01). In animal experiment,the levels of HO-1in brain and serum COHb were greatly elevated in HE groupcompared with BDL (p<0.01). Brain water content, PVP, ammonia in plasma and brainincreased in HE and Copp groups, but decreased following Znpp treatment (p<0.01).The AQP-4expression and oxidative stress extent in brain were reduced in Znpp treatment, and enhanced in Copp treatment (p<0.01).Conclusions: Inhibition expression of cerebral HO-1can reduce HE in rats. Themechanism might be ZnPP decreased AQP-4expression of astrocyte.