| Objective: To investigate the variation mechanics of heme oxygenase-1 (HO-1) and carbon monoxide (CO) and their liver function protection in obstructive jaundice through detecting the HO-1 mRNA expression in liver , heart and lung and plasma level of CO of rats with obstructive jaundice, and expression of HO-1 mRNA in liver of patients with obstructive jaundice.Material and Methods1. Specimen:Animal specimen: 48 male Wister rats (weighed from 260g-300g) were divided randomly into control group(CG), bile duct ligation 7-day group (7 d), bile duct ligation 14-day group(14 d) and bile duct ligation 21-day group (2Id). Subhepatic inferior caval vein blood, portal vein blood and hepatic vein blood were collected after 7, 14 and 21 days , at the same time, the liver, lung and heart were obtained.Clinical specimen: Hepatic tissues were obtained from 23 patients with obstructive jaundice during the operations, and 25 patients with chronic lithic cholecystitis who received simple cholecystectomy.2. MethodsHistology observation:Slice of paraffin embed tissue with HE stained was observed under microscope and cholangiectasis, blood sinus congestion, proliferation of fibrous tissue and inflammatory cell infiltration could be found.In situ hybridization:HO-l mRNA expression in liver, lung and heart of rats was detected with in situ hybridization, and the HO-1 mRNA expression in liver of patients with obstructive jaundice was detected with the same method.Double-wavelength spectrophotometer: the blood CO levels in the hepatic vein , the portal vein and the inferior vena cava was detected with double-wavelength spectrophotometer.3. Statistic analysis: The data was summarized as the mean s, statistical analysis was performed with F-test, q-test t-test and linear correlation with SPSS 10.0 software . A value of PO.05 was taken as getting the level of significant difference and that of .PO.01 was regarded as very significant difference.Results1. Animal experiment results:HO-1 mRNA expression:There are no HO-1 mRNA expression in liver, lung and heart of normal rats, and up-regulation of HO-1 mRNA in liver of rats with obstructive jaundice. The stain index of 7-day group, 14-day group and 21-day group were 0.10, 0.38 and 0.68. As the prolong of bile duct obstruction, its expression increased. The HO-1 mRNA expression levels in 14-day group and 21-day group were increased more significantly than that in 7-day group (P<0.01). There was only micro-expression in the heart of rats of 21-day group and no expression in 7-day and 14-day groups. There was no expression of HO-1 mRNA in the lung of rats of 7-day group; up regulation in the alveolar epithelial cells, bronchial mucosa cells and vascular endothelial cells of 14-day group and its expression reinforced further in 21-day group.Level of CO:There was a significant increase of the CO level of hepatic vein in the rats with jaundice in contrast to control group, especially in 14-day group and 21-day group (<0.01); The CO level of hepatic vein was higher than that of portal vein after ligating common bile duct (<0.01).2. Clinical study results:Compared with weak expression of HO-1 mRNA in hepatic cells of CG, its expression in those of obstructive jaundice groups was strong positive, especially around central veins.Conclusions:Up-regulation of HO-1 expression in liver of jaundiced rats and following high levels of CO in hepatic vein was correlated with damage of liver function and trouble of hepatic circulation, thus leading to the increase of hepatic blood flow. There maybe relationship between over expression of HO-1 mRNA and alteration of blood dynamics in lung of obstructive jaundice patients.The over expression of HO-1 mRNA in hepatic cells of obstructive jaundice patients could increase hepatic blood flow, improve hepatic circulation and alleviate the liver dysfunction.
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