| ObjectiveThe purpose of this study was to investigate the effects of the gentle liver manipulation,which including touching,retracting and moving liver lobes gently,on hepatic warm ischemia-reperfusion injury during hepatic ischemia and detect underlying mechanisms.MethodsThirty male Sprague-Dawley rats(225-250g) were divided into three group randomly:sham-operated group(Sham group),ischemia-reperfusion group(IR group) and manipulation group(MN group).In the Sham group (n=10) the livers underwent minimal dissection without futher procedure. The IR group (n=10) was produced by right liver lobe inflow occlusion for15min after minimal dissection and then left alone. To maintain standard conditions, gentle manipulation was carried out by the same surgeon touching, retracting, and moving the liver lobes for a specified time interval in the MN group (n=10) during15min ischemia described in the IR group. The reperfusion in each group was performed for2h. At the end of each procedure a blood sample was drawn from portal vein and right hepatectomy was performed following reperfusion. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in plasma and histopathologic examination were analyzed to assess damage in liver tissue. Portal and lobular inflammations were scored between0and3. The scoring system of histopathologic changes was:0=no inflammatory cells in portal or lobular space, and no hepatocyte necrosis;1=minimal focal inflammation or hepatocyte necrosis in portal or lobular space;2=moderate focal inflammation or hepatocyte necrosis in portal or lobular space; and3=severe focal inflammation or hepatocyte necrosis in portal or lobular space.The expression of Tumor necrosis factor-a and P-selectin in liver tissue were detected by immunohistochemistry S-P.All data were analyzed with SPSS17.0,P valus less than0.05were considered significant.ResultsThere were significant differences observed among three groups for all evaluation parameters.Plasma ALT levels were the following:Sham group,57.25±16.05U/L;IR group,251.87±50.80U/L, and MN group,366.75±89.45U/L. Plasma AST levels were the following:Sham group,76.50±12.38U/L;IR group,226.75±19.12U/L, and MN group,792.25±87.71U/L. Plasma ALT and AST levels of IR group and MN group were significantly higher than those of Sham group respectively(P<0.05); Plasma ALT and AST levels of MN group were significantly higher than those of IR group(P<0.05).Normal histologic findings were detected in the liver tissue of the rats in the Sham group(0.15±0.12). Focal inflammation in the portal or lobular space were detected in IR group(0.93±0.13). Severe focal inflammation or hepatocyte necrosis was observed in the portal or lobular space in the MN group(2.10±0.15). The score of IR group and MN group was significantly higher than that of the Sham group(P<0.05). The score of MN group was significantly higher than that of the IR group(P<0.05),indicating damage caused by gentle manipulation. The expression of Tumor necrosis factor-a and P-selectin in the IR group and MN group were significant higher than those in the Sham group respectively(P<0.05). The expression of Tumor necrosis factor-a and P-selectin in the MN group were significant higher than those in the IR group.(P<0.05)ConclusionsGentle in vivo liver manipulation including touching,retracting and moving liver lobes gently increases the reperfusion injury during hepatic ischemia.The underlying mechanisms by which gentle manipulation causes HIRI may be:Gentle manipulation may induced the expression of Tumor necrosis factor-α,which may cause hepatocellular injury by mediating direct toxicity to mitochondria and increasing liver oxygen consumption.Further more,gentle manipulation causes the increase in P-selectin up-regulation,thereby inducing neutrophil infiltration and increasing the microvascular disorders and finally causes hepatocellular injury. |
PDF Full Text Request