| Part 1 Effect of Ischemic Preconditioning on the expression of P-selectin in The Rat Liver with CirrhosisIschemic preconditioning (IPC) refers to a phenomenon in which a tissueis rendered resistant to the deleterious effects of prolonged ischemia and reperfusion(I/R)by prior exposure to brief periods of vascular occlusion.This phenomenon was first demonstrated in heart 15 years ago,and has been the subject of intensive investigation from then on.Although,the mechanism of IPC is still unclear up to now, several potential mediators (Nitrogen monoxide,Adenosine,Prostacyclin,Bradykinin and so on) are found to play different role in different organs. Adenosine and Protein kinase C (PKC)are critical to the beneficial actions of IPC in heart.IPC-induced adenosine Al-receptor stimulation during the period of preconditioning ischemia increases phospholipose C(PLC)activity,an event that is coupled by pertussis toxin-sentitive G proteins.Activation of PLC induces the formation of diacylglycerol,which in turn promotes the translocation and activation of PKC.Activation of PKC stimulates the activation of ATP-sensitive potassium (Katp) channels,and the beneficial actions of IPC in heart are induced.While adenosine stimulates NO production in IPC to protect against the injury associated with I/R in liver.Furthemore,NO improves microcirculation and attenuates the I/R injury of liver by inhibiting leukocyte-endothelial cell interaction,decreacing leukocyte rolling,adhesion and infiltrating.I/R injury results in release of inflammatory mediators which in turn cause the up-regulation of endothelial cell adhesion molecules and selectins that mediate platelet adhesion ,leukocyte rolling and adhesion.The final result is vascular stasis,tissue infiltration of leukocyte and generation of a great deal of oxygen radical and release of proteinase producted by leakocyte with subsequent organ damage.P-selectin was thought as a central mediator of leukocyte rolling and initial adhesion. Several researchs had revealed that rolling and adhesion of leakocyte were absent in P-selectin梔eficient mice following hepatic I/R injury and were inhibited by P-selectin antibody.P-selectin梞ediated rolling and initial adhesion were felt to result in firm adhesion and eventual emigration of leakocyte into hepatic parenchyma, followed by tissue destruction.Based on these knowledgements,we hypothesized that IPC abolished I/R induced leukocyte adhesion by preventing postischemic P-selectin expression via a NO-initiated pathway,However,The study similar to these hypothesions is scanty.This study aimed to determine the effects and mechanisms of IPC on the I/R injury of liver of cirrhosis rat and the effect of IPC on the expression of P-selectin. Materials and Methods1.Reproduction of the cirrhotic liver model of rattmale rats of the SD strain initially weighting 200+20g were used,subcutaneous injection of 60%Ccl4(0.3mg/kg)was once 4 days for 8 weeks and 5% ethanol was allowed to drink for 60 days.2.Operative Procedure:At first.ligementous attachments around the liver were dissected.The common bile duct was then cannulated and bile output was measured.Ischemia was induced in the median and left lateral hepatic lobes by clamping the correponding hepatic arterial and portal venous.While the blood flowing to the other lobe was left intact.When theassigned period of warm ischemia was completed,The clamp was removed and the pedicles to the non-ischemic lobe were ligated.3.Forty male SD rats with liver cirrhosis were allowed to 5 groups randomly:Sham Operation group(SO group),Ischemia/Reperfusion group(IR group) ,Ischemic Precontioning group (IPC group) ,L-Argine Preconditioning group (APC group) ,L-NAME Preconditioning group (NPC group), eight rats in each group.4.Hepatocellular viability was assessed by hepatic adenine nucleotide level and energy charge(EC) determined by HPLC, ALT-, AST, LDH mearsured by auto-biochemitry analyzer and bile output .The expression of P-selectin in the liver tissue was located and analyzed by im...
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