Effects Of The Inhibitor Of P38 MAPK Pre-processing And Post-processing On ICAM-1,TNF-α Induced By The Ischemia-Reperfusion Injury In Rat

Objective:1. To investigate the effects of the Ischemia-Reperfusion Injury on ICAM-1 and TNF-a expression of the serum of the Rat.2. To investigate the effects of the inhibitor of p38MAPK pre-processing and post-processing on ICAM-1 and TNF-a expression of the Rat induced by the Ischemia-Reperfusion Injury.Materials and methods:1. Grouping and medication:thirty-two healthy male Wistar Rat were distributed randomly by four groups:Sham, Ischemia-Reperfusion Injury of lower limbs, pharmacological precondition-ing, pharmacological postconditioning; Build the model of Ischemia-Reperfusion Injury of lower limbs by celiotomy and lipping abdominal aorta; pharmacological preconditioning and pharmacological postconditioning were induced by intravenous injection of the inhibitor of p38MAPK(SB203580)(lmg/kg) separately at 1 hour preoperation and at intraoperation. The other groups were induced by intravenous injection of the equivalent normal saline. Three observation time points are 0h,1h,3h after admission, on which time points collection.2. Malonaldehyde(MDA) was detected by thiobarbituric acid(TBA).3. The activity of the Superoxide Dismutase(SOD) was detected pyrogallol autoxidation.4. The concentration of ICAM-1 and TNF-αwas assayed by enzyme linked immunosorbent assay (ELISA).5. ICAM-1mRNA and TNF-amRNA were detected by RT-PCR.6. Phosphorylated P38MAPK of the gastrocnemius was detected by Western-blot.Results:ⅠThe building of the model of Ischemia-Reperfusion Injury in rats'lower limbs.The succeed of the model of Ischemia-Reperfusion Injury in rats'lower limbs was confirmed by the obvious higher MDA and the lower activity of the SOD.ⅡThe effects of the Ischemia-Reperfusion Injury on ICAM-1 and TNF-αexpression of the Rat. 1. The Ischemia-Reperfusion Injury led to a higher ICAM-1 and TNF-a expression compared with Sham dependently (P<0.05). And the highest point of ICAM-1 and TNF-a expression is 1h after admission.2. The Ischemia-Reperfusion Injury led to a higher Phosphorylated P38MAPK of the gastrocnemius expression compared with Sham (P<0.05).ⅢThe effects of the inhibitor of p38MAPK pre-processing and post-processing on ICAM-1 and TNF-a expression of the Rat induced by the Ischemia-Reperfusion Injury.1. Comparing with the control group, the inhibitor of p38MAPK significantly inhibited the expression of ICAM-1 and TNF-a concentration dependently (P<0.05). Comparing with the post-processing group, the inhibitory action of the pre-processing was obvious(P<0.05).2. Comparing with the control group, the inhibitor of p38MAPK significantly inhibited the expression of Phosphorylated P38MAPK of the gastrocnemius dependently (P<0.05). Comparing with the post-processing group, the inhibitory action of the pre-processing was obvious(P<0.05).Conclusions:1. Build the model of Ischemia-Reperfusion Injury of lower limbs successfully.2. The Ischemia-Reperfusion Injury of lower limbs led to a higher ICAM-1 and TNF-a expression, which provides favourable clues to the pathogenesis, cli-nical seriousness and prognosis of the Ischemia-Reperfusion Injury.3. Both the pre-processing and post-processing of the inhibitor of p38MAPK inhibited IR I-stimulated ICAM-1 and TNF-a expression, which indicates that the inhibitor of p38MA PK protect the Ischemia-Reperfusion Injury. The pre-processing group was superior to the post-processing group.