The Effect Of Deferoxamine Intervention On Hepatic And Pancreatic Function In Hepatic Blood Inflow Occlusion SD Rats

OBJECTIVE: To explore the effects of deferoxamine mesylate on liver and pancreas injury in SD rats which are caused by blocking the first porta hepatis through establishing an animal model by Blocking the first porta hepatis of Sprague-Dawley rats and to further explore the influencing mechanism of deferoxamine mesylate.To provide basis for the clinical application of deferoxamine mesylate in the treatment of hepatic ischemia-reperfusion injury and related pancreatic injury in liver surgery.METHODS: we select seventy healthy mature male SD rats from the animal research institute of Guangxi University school of Medicine.According to the random number method,we creat 3 groups: In the sham-operated group(10 animals),the rat’s abdominal cavity was opened after anesthesia and no other treatment was performed.The abdominal cavity was sutured 45 minutes later.In the saline pretreatment group(30 rats),an animal model of blocking the first liver portal was established after intraperitoneal injection of 2 ml physiological saline for 3 consecutive days before surgery.In the deferoxamine pretreatment group(30 rats): 200 mg/kg of deferoxamine was administered by body weight of SD rats for 3 consecutive days before blocking the first liver portal and then intraperitoneally injected after being diluted with physiological saline.The dose of the physiological saline was the same as that of the physiological saline pretreated group.The later two group were further divided into 3 subgroups respectively according to the time of sampling.Among each group,10 were collected on postoperative day 1,10 on the second postoperative day,and 10 on the third postoperative day.In the later two group,the first hepatic portal of rats was continuously blocked by the vascular clamp for 45 minutes,and the portal was restored after 45 minutes.The sham operation group was only performed wirh abdominal incision and suturing as a control.After these steps,10 rats in the sham operation group were collected specimens on postoperative day 1;the two pretreatment groups were respectively collected 10 specimens on postoperative day 1,10 on postoperative day 2,and 10 on postoperative day 3.The rat portal venous blood was collected and assayed by an automated blood biochemical analyzer for the content of three enzymes associated liver and pancreatic fuction.In addition,liver and pancreas tissues were divided into three copies,one left for HE staining of liver and pancreas,one for transmission electron microscope specimen to understand changes in pancreatic organelle levels,and one for determining MDA and SOD values in liver and pancreas tissues to understand liver and pancreas damage caused by blocking the first porta hepatis.RESULTS: on postoperative day 1,the MDA levels in liver and pancreas of the two pretreatment group were all significantly higher than the group without pretreatment,and the SOD content was less than the control group too(p<0.05).The MDA levels of the liver was significantly lower in the pretreatment group with deferoxamine mesylate on the first operational day than that in the normal saline preconditioning group(p<0.05).The SOD levels produced in the liver of the deferoxamine mesylate pretreatment group on the first operational day was significantly higher than the saline pretreatment group(p<0.05).as time passes,the MDA levels in hepatopancreas reduce gradually,while the SOD content rise gradually.on postoperative day 2,the MDA and SOD levels in the liver of the saline pretreatment group and the deferoxamine mesylate preconditioning group were statistically significant(P<0.05);The MDA levels in hepatopancreas of the pretreatment group was decreased to the normal range,while the MDA content in the normal saline pretreatment group was decreased to the normal range,and the MDA livel in liver was still high,However,differences between the amount of MDA in the saline pretreatment group and the deferoxamine mesylate pretreatment group and the sham operation group was statistically significant on 72 hours after operation,The SOD content in the hepatic tissue of the deferoxamine mesylate preconditioning group had risen to the normal value range 72 hours after the operation,while the SOD level in the pancreatic tissue of the deferoxamine mesylate pretreatment group did not rise to the normal range,but the SOD content in the hepatic tissue of the deferoxamine mesylate preconditioning group was still higher than that in the saline pretreatment group(p<0.05).On postoperative day 1,the AMY,ALT,and AST content in the saline preconditioning group and the deferoxamine mesylate pretreatment group were all significantly higher than those in the sham operation group,and the pretreatment group AMY and ALT in the mesylate were AMY and ALT.The amount of AST was significantly lower than that of saline pretreatment group(p<0.05).At 48 hours after surgery,the levels of AMY,ALT,and AST in the saline pretreatment group and the deferoxamine mesylate pretreatment group were all lower than before,and the AST levels in both groups had already dropped to the normal range.on postoperative day 3,the AMY levels in the saline pretreatment group and the deferoxamine mesylate pretreatment group were statistically significantly different from those in the sham operation group(p<0.01),The 72-hour AMY level in both groups was reduced,but it still did not rise to the normal range,and there was no significant difference between the deferoxamine mesylate preconditioning group and the saline pretreatment group;The ALT values in the saline pretreatment group and the deferoxamine mesylate pretreatment group had all dropped to normal values.HE staining: the hepatopancreas tissue of HE-stained sham-operated group was normal.on postoperative day 1,the liver tissue of the saline pretreated group showed large hepatic degeneration,necrosis,and inflammatory cells.Some pancreatic cells were seen to be swollen and necrotic in pancreatic cells with a small amount of inflammatory cell infiltrate.It was observed that hepatic pancreatic cells in the deferoxamine mesylate pretreatment group had less damage and the injury range was smaller.as time passes,the pathological changes of hepatocytes gradually decreased.SEM observation showed no abnormal changes in the cells of the pancreatic exocrine part of the sham-operated group.In the saline pretreatment group,the endoplasmic reticulum and mitochondria of the exocrine part of the pancreas were swollen.In the group without pretreatment,this phenomenon was less noticeable in the exocrine pancreatic cells.CONCLUTIONS:1.blocking the first liver portal can impaired liver and pancreas function;2.blocking the first liver portal can cause the ischemiareperfusion injury of liver and pancreas issue;3.the deferoxamine mesylate pretreatment has a protective effect on blocking the liver and pancreas damage associated with blocking the first liver portal.