Abstract:

BACKGROUND: Previous studies demonstrated that adrenomedullin (ADM) drugs have protective effects on organ ischemia-reperfusion (IR), but, it remains unclear whether ADM gene transfer have protective effect on liver following limb IR.
OBJECTIVE: To explore the effect of pVAX1-ADM on rat liver following limb IR.
METHODS: Totally 32 adult male SD rats were randomly divided into 4 groups: namely, sham-surgery, IR model, pVAX1-ADM and empty vector groups, with 8 animals in each group. All rats were prepared for IR models except the sham-surgery group. pVAX1 and pVAX1-ADM were injected into rat gaspartate aminotransferase rocnemius in the pVAX1-ADM and empty groups; physiologic saline were injected into rats in the sham-surgery and IR model groups. The contents of plasma glutamic-pyruvic transaminase (GPT), glutamic-oxal(o)acetic transaminase (GOT) and lactic acid dehydrogenase were measured after reperfusion, and the levels of superoxide dismutase (SOD), malonaldehyde of liver were determined; the expression of ADM in operated gastrocnemius muscle was detected by immunohistochemistry; the morphological changes of liver tissues were observed under a microscope.
RESULTS AND CONCLUSION: Compared with the sham-surgery group, the contents of plasma GPT, GOT, lactic acid. dehydrogenase, and liver malonaldehyde in the IR model group were obviously increased (P < 0.01), and the SOD activity were notably decreased (P < 0.01). The tissue damage was obviously observed with microscope, such as the signs of liver cells edema and structural disorder. Compared with the IR model group, contents of plasma GPT, GOT, lactic acid dehydrogenase, and liver malonaldehyde in the pVAX1-ADM group were obviously decreased (P < 0.01), and the SOD activity were notably increased (P < 0.01), the tissue damages of hepatocytes had improved. Immunohistochemistrical results demonstrated that expression of ADM was up-regulated in the pVAX1-ADM group. These results show that the adrenomedullin gene transfer has protective effect on remote liver injury due to hindlimb ischemia-reperfusion injury, which may be related to increased anti-oxidative capacity and reduced seepage of liver enzyme.