| Objective and background:Anastomotic leakage is one of the common complications after intestinal resection and anastomosis.Because of the left colon and rectum in anatomy and physiology on the intestinal wall thin,poor blood supply,enterobacteria,high pressure,the incidence of anastomotic leakage in left colon and rectum is higher than small intestine and right colon.According to the statistics of China's colorectal anastomotic leakage rate is about2%~ 14%,and in low rectal carcinoma incidence of anastomotic leakage can be as high as 15% ~ 26%.Previous studies have shown that the main factors that affect the healing of the wound:(1)Local factors: Bad microcirculation,anastomotic suture tension is too hige,the anastomotic tissue alignment is poor,local infection,radiation injury,distal intestinal obstruction etc.(2)Systemic factors: Malnutrition,blood flow,(3)Technical factors.In addition the suture technique of operators,the local factor plays the most important role in promoting the healing of stoma.Anastomotic tension suture and excessive vascularization at the distal end of the anastomosis resulted in inadequate local blood supply.The results showed that the ischemic injury of the gastrointestinal tract resulted in the slow healing of the anastomosis and increased the incidence of local infection.Eventually make the incidence of anastomotic leakage increased.Early detection and intervention can often benefit patients,but there is still a lack of effective means of early detection.Based on the present situation of postoperative anastomotic leakage prevention and control measures are not particularly targeted.We are aware of the need to speed up the study to promote the healing of intestinal anastomosis after surgery.Therefore,in addition to the traditional operation method,we should also continue to seek other ways to prevent and treat the occurrence of anastomotic leakage and development.This is why our use gabexate mesilate on inflammatory inhibition,promote fiber healing and improving microcirculation function,to observe the changes of intestinal healing process in rabbits.So as to provide some experimental basis for reducing the incidence of anastomotic leakage.The occurrence of anastomotic leakage was closely related to the tissue ischemia reperfusion(Ischemia-reperfusion injury;IRI).While the process of tissue ischemia and reperfusion can cause severe inflammatory reaction.Gabexate mesilate in 1980 s is a non peptide synthetic protease inhibitor,can effectively inhibit the synthesis of plasma kallikrein,trypsin and plasmin.The above products can be rapidly activated enzyme and its expression in trauma,infection,endotoxin and other causes of action,and then increase the capillary permeability caused by inflammatory cell infiltration,induced a strong inflammatory response.There are also reports that gabexate mesilate on ischemia reperfusion injury(DIC)there is a certain role in the prevention and treatment.Miyagi S et al found that Gabexate mesylate also has protective effects on vascular endothelial cells.To sum up,Gabexate mesylate has certain effects on the inhibition of inflammation,the treatment of tissue ischemia reperfusion injury and the protection of vascular endothelial cells.It has been widely used in the treatment of acute pancreatitis,and a large number of studies have shown that it has a certain role in the inhibition of acute inflammatory response and improve microcirculation and so on.Therefore we assume that the role of using Gabexate mesilate in inflammation inhibited,protect endothelial cells and improve microcirculation.The rabbit intestinal injury model,were given Gabexate mesylate as intervention measure of Mugabe fat in the gut injury in whether can promote the healing and action mechanism.Finally to resection in the colon lesions,intestinal anastomosis after surgery to be effective intervention and relieve the intestinal inflammation and promote the healing of stoma,and the risk in patients with systemic inflammatory reaction,reduce and improve the prognosis of patients,reduce the complications related to the proposed method to follow.Materials and methods:Animal grouping and model preparation:24 New Zealand rabbits(male and female),weighing about(2 + /-)kg,were randomly divided into experimental group and control group,each group of 12.All animals were fasted before 12 h.Lying on the operating table.Preoperative skin preparation,disinfection shop towels,by the ear vein injection concentration of 25% urethane(1000mg/kg dose).After Anesthesia satisfied,in the upper abdominal incision into the abdomen,about 5 ~ 6cm.Take out transverse colon without cutting the mesenteric vascular edge.Use the 4/0 thread after transection terminoterminal anastomosis with whole layer,stitch and margin were0.3cm.After the anastomosis,the normal saline 100 ml was used to flush out the local abdominal cavity.Continuous suture of abdominal wall with3/0 wires.The indwelling needle was placed on the marginal vein of the ear,and the model was established.30 minutes after surgery,the experimental group injected the Gabexate mesilate by the Marginal vein of ear(Dose according to 40mg/kg).Every 12 h again after bolus injection of the same dose of gabexate mesilate,until killed.30 minutes after surgery,The control group injected the 0.9% Sodium Chloride Solution by the Marginal vein of ear(Equal volume with the experimental group).Every Marginal vein of ear(Equal volume with the experimental group).Every 0.9% hours after the injection of the same amount of 12 h Sodium Chloride Solution,until killedexperimental observation and detection methods:The two group after third and 5 days every 6 rabbits were killed(intravenous injection of anesthetic and excess air),for the following observation:Observe the abdominal cavity and anastomosis of the general situation: After caesarean section in the eyes of the intra-abdominal condition was initially identified.To observe the abdominal cavity and anastomotic abscess by adhesion,and the existence of crevasse situation.recording and imaging.Histopathological examination:The pathological specimens were made by anastomosis,10% formalin fixed,paraffin embedded sections,HE and Masson staining.H&E staining was used to observe the infiltration of inflammatory cells,the activity of fibroblasts and the infiltration of red blood cells.Masson staining was used to observe the proliferation of collagen connective tissue.The modified Ehrlich and Hunt grade 0-4score was evaluated.experimental result:Results From general and pathological observation: There was no fluid in the peritoneal cavity,and a few of the cellulose in the anastomotic stoma were leaking around the stoma.However,these adhesions were easily removed from the anastomosis,and the control group was more compact than the experimental group.Both groups were no obvious signs of anastomotic purulent infection,no break,there was no intra-abdominal intestinal contents.On the third day after operation,the surface of intestinal tissue in the experimental group was clean and tidy,with no obvious congestion and edema.In the control group,the degree of congestion and edema of the tissue was more serious,and the surface of the tissue was more disordered.On the fifth day after operation,the tissue congestion and inflammatory exudation were improved,and a small amount of pus was found in the anastomotic site,and there was no significant difference between the control group and the other two groups;H&E staining results: On the third day after surgery,the infiltration of inflammatory cells and the infiltration of red blood cells in the experimental group were significant.While the inflammatory cell infiltration and red blood cell infiltration in the control group were lighter than that in the experimental group,and there was no activity of fibroblast cells.After fifth days,the inflammatory cell infiltration and the infiltration of the red blood cells in the two groups were significantly relieved.There were still more inflammatory cells in the mucosa of the experimental group,the blood flow of the newborn capillaries was more abundant than that of the control group,and the proliferation of fibroblast was obvious.In the control group,a large number of inflammatory cells were found in the mucosa of the control group,and the degree of fibroblast proliferation was lower than that in the experimental group;Masson staining results: On the third day after surgery,the visible serosal and muscle layer collagen fibers are widely distributed,obvious staining,width compared with those in control group;For the control group,the subserous and muscular layer of collagen fibers was zonal distribution,width was significantly narrower in the experimental group.On the fifth day after operation,the collagen fibers were widely distributed.empirical conclusion:GM can promote healing of rabbit transverse colon anastomosis and reduce anastomotic leakage by accelerating the process of early inflammation through improve blood circulation,inhibitory inflammation in the late healing,promote fibroblast proliferation and promote the synthesis of collagen fibers. |
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