Effects Of Partial Hepatic Ischemia/Reperfusion Injury On Postoperative Cognitive Function In Mice

Objective To investigate the effect of partial hepatic ischemia/reperfusion on postoperative cognitive function and the expressions of nuclear factor-κB (NF-κB) and choline acetyltransferase (ChAT) in the hippocampus of mice.Methods Eighty mice (age: 2–3 months) weighing 20-25g were used in these experiments. Two atraumatic clips were used to prevent blood supply to the left artery and portal vein of the hepatic for setting up 70% of hepatic ischemia / reperfusion injury model. After blocking,the tail blood pressure were monitored by BP-98A during the ischemia / reperfusion period, and the blood pressure block area can be seen by color of hepatic from bright red to dark red indicates that ischemia is successes. Mice were randomly divided into four experimental groups each containing twenty mice. Sham group (S, n=20): a sham operation was performed (except for hepatic I/R). I/R groups (I/R1, I/R2,I/R3 ,n=20): mice underwent hepatic ischemia for 20,30,40 min,then atraumatic clips were removed for 30min reperfusion. Blood samples and hepatic ischemia tissues were obtained at the end of reperfusion to assess serum and hepatic tissue homogenate aminotransferase (ALT), aspartate aminotransferase (AST).I/R groups were treated by anti inflammatory therapy for three days. Then each group branched out 10 mice for morris water maze and step-through test from the 4th day to the 11th day, and the rest mice tested them from the 11th day to the 18th day. The mice were perfused with 4% paraformaldehyde after 1h of the last morris water maze to get hippocampals to observe and analyze the hippocampal neurons structure and the expressions of NF-κB and ChAT in hippocampal using Nissle and immuno-histochemical staining. Finally, all data were expressed as mean±SD. The statistical significance of differences between groups were analyzed using the oneway analysis of variance (ANOVA) with the SPSS13.0 for windows XP statistical software package. The P values less than 0.05 was considered statistically significant.Result Compared with Sham group, I/ R groups at ischemic 20,30,40min, reperfusion after 30min ALT and AST activity was significantly increased in serum and hepatic tissue homogenate(P< 0.01 or P<0.05 ). Compared with I/ R 3 , I/R1 and I/R2 were markedly decreased ALT and AST activity in serum and hepatic tissue homogenate(P<0.05). Compared with sham group, the occluded hepatic tissue from I/R groups was markedly damaged characterized by mitochondrion swellen, vacuolar degenerationand, mitochondrial crista destruction, rough endoplasmic reticulum markedly decreased and nucleusstructure destruction under the electron microscope, and the prolong of the ischemia time resulted in a significant labefaction of hepatic injury. Compared with the the escape latency of Sham group, this in I/R1 or I/R2 was significantly longer at days 5,6,7,8 and 9 than this in Sham group (P <0.05),and this in I/R3 was significantly longer at days 5,6,7,8 ,9 and 10 than this in Sham group(P <0.05).while on the 11th day, there was no significantly statistical difference among Sham group and I/R groups.Compared with the piercing numbers, average speed, central swimming distance and swimming time of spatial probe of Sham group, there was no significantly statistical difference among Sham group ,I/R1 and I/R2 , this in I/R3 was obviously shorter than this in Sham group (P<0.01),and there was no significantly statistical difference among three groups of on the18th day.Compared with Sham group, the incubation period and the number of errors were significantly longer in I/R1 and I/R2 than those in Sham group at days 5,6 and 7 (p<0.05); those in I/R3 were significantly longer than those in Sham group at days 4,5,6,7 and 8(p<0.05). The hippocampal neurons of I/R3 arranged neatly in Nissle stainingaining of hippocampu, and there was no obvious abnormalities in the nuclear and chromatin, but the cytoplasm were slightly edema, while the hippocampal neurons of other groups of mice arranged neatly and closely, and the structure had no obvious abnormalities. Compared with Sham group, the ChAT positive neurons in the hippocampus of I/R groups were decreased significantly (P<0.01),their expression was the least in I/R3; and there was no significantly statistical difference between I/R1 and I/R2. Compared with Sham group, the NF-κB positive neurons in the hippocampus of I/R groups were increased significantly (P<0.01),their expression was the most in I/R3; and there was no significantly statistical difference between I/R1 and I/R2.The expressions of ChAT and NF-κB in hippocampus had no significantly difference on the 18th day.Conclusion Partial hepatic ischemia/reperfusion injury leads to a short term postoperative cognitive dysfunction in mice, this cognitive dysfunction lasted about 11days. And partial hepatic ischemia/reperfusion injury show some effects on ChAT and NF-κB expressions in hippocampus of mice.