Protective of combination preconditioning on renal ischemia-reperfusion injury in rats

Objective To investigate the effect of Anti TNF-α combined with p38MAPK antisense oligonucleotide on renal funtion and TNF- α, p38MAPK protein expression at different ischemia-reperfusion points. Methods One hundred and twenty normal male Sprague-Dawley rats were divided into 4 groups by simple randomization: sham-operated(sham)group, ischemia-reperfusion(IR)group, Anti TNF-α+ ischemia-reperfusion(Anti TNF-α+ IR)group, Anti TNF-α and p38MAPK antisense oligonucleotide + ischemia-reperfusion(combination preconditioning+ IR) group.Each group comprised 30 rats. Anti TNF-α+ IR group was subjected to ischemia-reperfusion injury with intravenous administration of Anti TNF-α(0.1 mg/kg)5min before reperfusion.Combination preconditioning+ IR group was subjected to ischemia-reperfusion injury with intravenous administration of Anti TNF-α(0.1 mg/kg)and p38MAPK antisense oligonucleotide (5 mg/kg)5 min before reperfusion.IR group with the same injury was followed by saline administration in the same manner.Sham group was subjected to only anesthetization but not to ischemia.Detecting the plasma creatinine and plasma urea nitrogen and two-step inmunohistochemical methods were used to detect the changes of expression of TNF- α, p38MAPK. The measurement data were compared with the t test and the count data were compared with Chi-square test. The date were expressed by (±s). Intergroup comparison translated by variance analysis. Results After reperfusion, the plasma urea nitrogen in the IR group was (15.86±2.41), (21.13±2.21), (25.47±2.29), (30.51±2.03), (35.56±2.47) μmol/L at 0, 1, 3, 6 and 12 h, respectively, and was (25.61±5.40), (32.48±2.30)(68.20±1.20), (84.42±2.43), (96.15±2.23)at 0, 1, 3, 6 and 12 h respectively, and still showed an increasing trend at 12 h. TNF- α mainly expressed in renal proximal convoluted tubules, gradually upregulate with duration of ischemia-reperfusion to 12h of reperfusion. p38MAPK mainly located at distal convoluted tubules, peaked at 6h of reperfusion. But these effects were offset by administration in combination preconditioning group (P<0.05). Conclusion Renal ischemia-reperfusion injury can be alleviated by Anti TNF-α and p38MAPK antisense oligonucleotide treatment. Key words: Reperfusion injury; Kidney; Ischemia; Tumor necrosis factor