| Peritoneal adhesion is one of the important complications following laparotomy and may lead to harmful results such as intestinal obstruction, infertility, and chronic abdominal pain, etc. Many efforts have been dedicated to reduce adhesion formation due to these complications and high morbidity. So the prevention of postoperative peritoneal adhesions is the urgent and tough problem in the surgery area.There have been some drugs to prevent postoperative peritoneal adhesions, but each of them has some severe defects. Chitosan, the N-deacetylated derivative of chitin, has been recommended as a suitable functional material because of its biocompatibility, biodegradability, reliability, thermotolerance, adsorpable properties and wide sources. Furthermore, chitosan have many virtues, such as antibioltic effect, promoting blood coagulantion, as well as suppressing cicatrix formation. However, the low solubility of chitosan limited its application. DCX-16 is a new chemical derivate with high solubility. The aim of this study was to evaluate the effects of DCX-16 to prevent the formation of peritoneal adhesions and explore its molecular mechanisms.METHODS:A rat cecum abrased wound model was used to examine the prophylactic effects of different concentration DCX-16 during adhesion formation at different times after abdominal operation. Adhesions were generated in rats by injuring the surface of the cecum with dry gauze. Rats were randomly devided into different groups. Several experiments were designed to study the effects of DCX-16 administrated during the laparotomy and at 3rd day postoperation. The adhesions were observed and graded at 3,7,14 and 21 days afer injury and assessed with histological evaluation by HE and Van Gieson staining. The collagen densities were measured with Image-Proplus. Transforming growth factor-beta1 (TGF-beta1), fibronectin(FN), matrix metalloproteinase-1(MMT-1) and tissue inhibitor of matrix metalloproteinase-1(TIMP-1) were determined with immunohistochemistry technique. Tissue-type plasminogen activator (t-PA) activity, plasminogen activator inhibitor(PAI) activity, malondialdehyde content, superoxide dismutase activity and tissue hydroxyproline content were measured with chromophore substrate method, TBA method, nitrite salt method and digestive method respectively. In addition, the safety and cytotoxicity of DCX-16 were also evaluated.RESULTS:There was no obvious adhesion at 3 days postoperation. The peritoneal adhesions formed at 7th day postoperateion in control group. DCX-16 inhibited the formation of adhesions significantly, decreased infiltration of leukocytes and peritoneum fibroblasts proliferation. The contents of collagen and fibrous tissue in control group increased markedly from 3rd to 21th day after operation and DCX-16 decreased them significantly. The contents of tissue hydroxyproline in treated group decreased significantly compared with control group from 3rd day to 21th day after laparotomy. DCX-16 significantly increased the expression of t-PA and decreased the expression of peritoneal plasminogen activator inhibitor type 1 (PAI-1) at 3rd and 7th day after after laparotomy. DCX-16 also markedly reduced the level of TGF-beta1, FN, TIMP-1, enhanced the expression of MMP-1 in cecum tissue after laparotomy. There were not significant differences in abdominal wall incisions between the experimental groups and control group. DCX-16 significantly decreased the levels of MDA and increased the activities of SOD in blood plasma at 3rd day and 7th day after laparotomy. It was also showed that DCX-16 had no stimulation on eyes, skin and muscles in rabbits. Tolerance dose of DCX-16 in mice was as high as 3g/kg. All of the treated mice survived. Cell culture with DCX-16 demonstrated 3T3 cell's shape and growth were normal. The relative growth rate of 3T3 cells had no statistical difference between control and DCX-16 groups.CONCLUSION: 1. DCX-16 could obviously decrease the incidence and extent of intraabdominal adhesions after laparotomy.2. DCX-16 could prevent th...
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