| Part â… Wether the Aged rat Liver Exist the Chronic Oxidative Stress andLipid Peroxidation State ObjectiveTo study Wether the Aged rat Liver Exist the Chronic Oxidative Stress and Lipid Peroxidation State, and explain why the aged rat liver has the serious ischemia-reperfusion injury with the "the second hit" theory.MethodsTotal glutathione (GSH), tocopherol (TOC), ascorbic acid (AA), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyd (MDA) were measured in the livers of aged and adult rats (n=5 each).Results1. The activity of SOD (479.24±9.08 U/mg prot) in aged rats liver is significantly decreased than that in adult rats liver (619.80±65.54 U/mg prot).2. There were no significant differences in activity of CAT between the 2 groups.3. Aged rat liver contained significantly less GSH (29.6±2.07 mg/mg prot) in comparison with adult rats liver (36.7±4.58 mg/mg prot).4. There were no significant differences in TOC content between the 2 groups.5. Aged rat liver contained significantly less AA (1.99±0.25 ug/mg prot) in comparison with adult rats liver (3.15±0.67 ug/mg prot).6. Aged rat liver contained significantly more MDA (1.30±0.08 nmol/mg prot) in comparison with adult rats liver (1.05±0.20 nmol/mg prot).7. The activity of GSH-Px in aged rats liver (40.78±0.84 U/mg prot) is significantly decreased than that in adult rats liver (68.67±8.49U/mg prot).ConclusionThe aged rat liver exist the chronic oxidative stress and lipid peroxidation State, because the ability of antioxygen is decreased, when the acute oxidative stress happened, it can not resist the aggression of ROI sufficiently, so the severe ischemia-reperfusion happened.Part â…¡Alleviating the Ischemia-Reperfusion Injury in Aged Rat Liver by Induction of Heme Oxygenase-1 with Hemin ObjectiveTo study wether the induction of HO-1 with Hemin can alleviate the ischemia-reperfusion injury in aged rat liver, and approach the mechanism of HO-1.Methods1, Syngeneic liver transplantation was performed using liver that were harvested from aged rat and stored for 6 h at 4°C in University of Wisconsin solution before being transplantation into recipient ,There were three treatment groups. In group 1 donors (n=25) received hemin (125mg/kg) , an HO-1 inducer 24 h before procurement. Group 3, prospective liver donors (n=25) were given saline 24 h before liver harvest. After 6 h of storage at 4 °C in University of Wisconsin solution, livers in both groups were then transplanted into rat. Group 2 donors (n=25) were treated with hemin 24 h before harvest. After 6 h of cold storage, livers were transplanted into rats, which were then infused with ZnPP (1.5 mg/kg I v), an HO-1 inhibitor, at the end of surgery after unclamping the vessel. Separate groups of rats (n=5/group) were killed at 3, 6, 12, 24 and 48 h after unclamping.2, Detect the ALT and NO in plasm , determine the activity of HO-1, observate the histological change with light microscope and electron microscope, detect the apopotosis with TUNEL assay, and the express of Bcl-2, Caspase-3, eNOS, iNOS with Western-blot.Results1 , The ALT levels in hemin group was significantly decreased than that in saline and Hemin+ZnPP group at any time point after reperfusion2, 3, 6, 12 hr after reperfusion, the plasma NOx levels in the hemin group were significantly lower than those in the saline and hemin+Znpp group (P<0.05), At 24, 48 hr after reperfusion, the plasma NOx level in the control group was almost the same as that in the hemin group.3 , pretreatment with hemin significantly increased HO-1 liver activity after transplantation, Adjunctive ZnPP given at reperfusion inhibited HO-1 activity in liver grafts.4, Six hours after reperfusion, livers pretreated with saline showed severe disruption of lobular architecture, significant periportal edema, the vacuole type degeneration, comparable with hemin group. Six hours after reperfusion, specimens in the control group were evaluated by electron microscopy. It shows that there has a great qu... |
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