The Protective Mechanism Of Metallothionein(TM) On Hepatic Ischemia-reperfusion Injury In Rats

Hepatic ischemia-reperfusion injury is that the blood flow of liver tissue blood flowrestored after ischemia for a period of time, damage was further aggravated, evenirreversible. Ischemia-reperfusion (IR) injury is a major cause of morbidity andmortality in patients with hepatic compromise. But there is still no effective clinicalprevention and treatment measures. Hepatic ischemia-reperfusion injury is amultifactorial pathophysiological process, and free radical damage and inflammatoryresponse was the key factors in ischemic reperfusion injury. Metallothionein (MT) is alow molecular weight, thiol-rich metal-binding proteins, MT can scaveng free radicaland provide protection against lipid peroxidation. Rencently, study ofischemia-reperfusion injury in cardiac muscle, spinal cord, skeletal muscle and brainhad shown a protective effect of MT, but the role of MT in hepatic ischemia-reperfusioninjury rarely reported.In this study, MT was used for the pretreatment of the rats to explore the functionalmechanisms of MT on hepatic ischemia-reperfusion injury. First, hepaticischemia-reperfusion model was established by improving Nauta method. The activitiesof aspartate aminotransferase (AST), alanine aminotransferase (ALT) in serum weremeasured by automatic biochemistry analyzer and the pathomorphological changes ofliver tissue were observed by the light microscope, and by these ways, the role of MTon hepatic ischemia-reperfusion injury in rats was measured. Secondly, liver plasmawas prepared. The levels of malondialdehyde (MDA) in liver plasma were measured byTBA method. The activities of antioxidant enzymes of superoxide dismutase (SOD),content of GSH and the inhibition of·OH activity in liver plasma were detectedrespectively by corresponding kits. At last, the levels of NF-κB, TNF-αand ICAM-1mRNA were observed by real time quantitive fluorescence PCR in this study.The results suggest that MT has the protective effect against the experimentalhepatic ischemia-reperfusion injury in rats. The mechanisms may due to the MTantioxidant activities and anti-inflammative activities. MT can stimulate hepaticantioxidant enzymes activities and removing·OH free radicals generated in theprocessing of ischemia-reperfusion, suppressing lipid peroxidation of membrane,decreasing the level of MDA. Moreover, MT can inhibit the expression of NF-κB,TNF-αand ICAM-1 mRNA in liver, thereby protect against hepatocyteischemia-reperfusion damage.