Effects Of Dexmedetomidine On Liver Injury Induced By Intestinal Ischemia-reperfusion In Rats

Objective: To study the protection and mechanism of dexmedetomidine on intestinal ischemia reperfusion liver injury in rates.Methods : Depuratory adult healthy male Sprague-Dawley(SD)rats selected were randomly divided into 4 groups,including sham operation group(Sham),ischemia/reperfusion group(I/R),ischemia/reperfusion group along with 2.5ug/(kg/h)dexmedetomidine precondition group(I/R+ DL)and ischemia/reperfusion group along with 5ug/(kg/h)dexmedetomidine precondition group(I/R +(DH).Sham group was provided with SMA seperation without clipping,and the peritoneal was closed 60 min after operation.The ischemia/reperfusion model was prepared by I/R group and dexmedetomidine treatment group by reperfusion after clipping superior mesenteric artery(SMA)for 90 min.I/R + DL group and I/R + DH group were provided with dexmedetomidine 2.5ug/(kg/h)and 5ug/(kg/h)Caudal vein infusion 1h prior to operation.Group I/R,the tail vein was infused with the same amount of saline 1 hours before surgery.8 rats were randomly selected from each group 2 hours after reperfusion.Liver tissue of these rats were sampled,stained with haematoxylin and eosin,and observed for pathologic changes of liver under light microscope.Western blotting were adopted to test expression level of pro-apoptotic protein(caspase-3)and dUTP induced by in situ terminal deoxyribotide transferase.Neck-end labeling(TUNEL)was adopted to test hepatocyte apoptosis and calculate apoptosis index.The level of alanine aminotransferase(ALT),aspartate aminotransferase(AST),lactate dehydrogenase(LDH),interleukin-6(IL-6)and tumor necrosises factor-a(TNF-a)were tested.Meanwhile,the activity of liver reactive oxygen species(ROS),malonydialdehyde(MDA)content,superoxide dismutase(SOD)and myeloperoxidase(MPO)were tested as well.Results: Compared to Sham group,I/R group,DL group and DH group had obvious liver injury,and the cleaved caspase 3 protein expression,apoptosis index,ROS,MDA,IL-6,TNF-α and MPO content had increased significantly with lower activity of SOD.The difference had statistical significance(P<0.05 or0.01).Compared to I/R group,DL group and DH group had significant improvement in the above indicators,and the difference had statistical significance(P<0.05 or 0.01).Compared to DL group,DH group had improvement in the above indicators to some extent,and the difference had statistical significance(P<0.05 or 0.01).Conclusion:1.Intestinal ischemia-reperfusion can induce remote liver injury.2.Dexmedetomidine can protect rats from liver injury caused by ischemia/reperfusion,and such protection may have dose-dependent.3.The mechanism may be related to inhibiting inflammatory response to some extent,oxidative stress injury and hepatocyte apoptosis.