Adenovirus-mediated Human Heme Oxygenase-1 Gene Transfer in Bile-duct Ligated Animals

• Main Authors: Ya-Ling Chen, 陳雅鈴
• Other Authors: Shu-Chu Shiesh
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/62636648869320135043

碩士 === 國立成功大學 === 醫事技術學系 === 93 === 　　Cholestasis is a pathologic state of reduced bile formation or flow that occurs in many human liver diseases. Growing evidence suggests that considerable destruction of oxidative stress regulation may play an important role in cholestatic liver injury. Heme oxygenase-1 (HO-1) is the inducible and rate-limiting enzyme which catalyzes the oxidative degradation of heme. Evidence has been shown that HO-1 plays a pivotal role in anti-inflammatory, anti-apoptosis, and cytoprotective defense mechanism against oxidative stress. Elevated HO-1 expression in the liver was found in bile duct ligation aminals. However, it is not known whether the induction of HO-1 exogenously would protect the liver from damage of cholestasis. Therefore, it was the aim of the study, by the use of a bile duct-ligated model of cholestatsis in mice, to investigate the protective role of HO-1 and it’s mechanism. We constructed a human HO-1 (hHO-1) recombinant adenovirus (Ad-hHO-1) and examined the phenotypes of exogenous hHO-1 overexpression in mice with bile duct ligation (BDL). The common bile duct ligated ICR mice were pretreated with CoCl2 as a HO-1 inducer or recombinant adenovirus by intraperitoneal administration and sacrificed in 1, 3, 7, or 14 days after BDL. The HO-1 expression of Ad-hHO-1 was confirmed by western blotting. Serum levels of AST, ALT and bilirubin and the pathological changes were examined to monitor the damage in liver in BDL animal model. Compared with BDL group, the serum level of AST in Ad-hHO-1 group was decreased (896±351 U/L v.s 449±146, p=0.01) in 7 days after BDL. The ALT in Ad-hHO-1 groups was also decreased (999±335 U/L v.s. 554±193 p=0.01). Similar result of ALT level was found in BDL with CoCl2 administration (999±335 U/L v.s 557±177, p=0.015). We found that CoCl2 or Ad-hHO-1 administration could reduce the liver injury during cholesatsis and the serum levels of AST, ALT. In conclusion, HO-1 overexpression using chemical induction or adenovirus transfer could reduce the liver injury during cholestasis.