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Investigation Of The Preventive Effect Of PEG-CNP-TR On Abdominal Adhesions Of Rats

Posted on:2018-05-02Degree:MasterType:Thesis
Country:ChinaCandidate:K LiuFull Text:PDF
GTID:2334330515976275Subject:Biopharmaceuticals
Abstract/Summary:PDF Full Text Request
Peritoneal adhesion is one of the most common complications after abdominal surgery,as well as the most urgent challenge being solved in surgery.The majority of peritoneal adhesions is caused by abdominal surgery,which could damage tissues,change the internal environment of abdominal cavity and upset the dynamic balance of fibrinolysis.Together with oxidative stress and inflammatory reaction,those factors contribute to the final formation of adhesion.At present the single component preparation flush fluid is widely applied in clinic treatment,but still couldn't effectively prevent or treat abdominal adhesion.In this research,the preventive effect of a new compound biological flush fluid PEG-CNP-TR(PCT)on abdominal adhesion modelling rats was investigated which aims to support the application of PCT in clinical research.The drug toxicity,safety and biocompatibility of this new drug were also studied.The peritoneal adhesion modeling was prepared via abdominal surgery.90 male Wistar rats were randomly divided into 9 groups: Control group(Control,n=10),without any treatment;Sham operation group(Sham,n=10),only with abdominal suture treatment;Model group(Model,n=10),after surgery 2 m L saline was applied on cecal scratches and wound of abdominal wall;Rats of Surg Take Solution group(STS,n=10),Hemostatic Sponge group(HS,n=10)and Chitin Surgical Flushing Liguar group(CSFL,n=10)were treated by abdominal surgery in the same way,then 2 m L of the corresponding drugs were postoperatively applied on the damaged surfaces,respectively;three groups of rats(Low PCT,Medium PCT,High PCT,each group n=10)were operated,the cecal scratches and wounds of abdominal walls of all rats of the three groups were applied with 1 m L PCT,2 m L PCT and 3 m L PCT,respectively.All rats were sacrificed at 14 th day after operation.The level of adhesion was evaluated.H&E staining was performed on the cecal tissues with adhesions.The whole blood,plasma and serum of rats were analyzed.The grade of model groups showed higher level of adhesion compared with control groups.Three doses of PCT groups showed lower adhesion grade than model groups.Macroscopic pathology of model groups showed that serosal layers were broken seriously.The adhesion tissue was full filled with large number of inflammatory factors.But in the three groups with different doses of PCT showed clearly cecum wall structure.The inflammatory factors in intestinal wall tissue adhesion showed lower than that of control groups.Fibrinolytic system is able to dissolve fibrin clots.Once the dynamic equilibrium of fibrinolytic system is broken,soluble fibrinogen transform into insoluble fibrin and further form adhesion.Fibrinogen(FIB)and plasminogen activator(t-PA)were detected in rat plasma by ELISA.The results showed that,in Model group the content of FIB increased(p<0.001)and the content of t-PA decreased significantly(p<0.001).By contrast,the three groups of PCT revealed certain preventive effects on postoperative adhesion.Oxidative stress is also one of the causes of adhesion,by lesions inflammatory factors could be highly expressed under hypoxia condition.In this study,the enzymes regulating free oxygen radical were detected by adopts spectrophotometer and ELISA.Compare to the Control group,the expressions of Malondialdehyde(MDA)and cyclooxygenase-2(COX-2)in the Model group were significantly increased(p<0.05,p<0.01,p<0.001).But in the three groups with different doses of PCT showed observably decreasing of inflammatory factors at different levels.Thus,PCT is supposed to be able to inhibit oxidative stress and further prevent adhesion.Inflammatory factors play an important role in adhesion.To support further study,interleukin-6(IL-6)and transforming growth factor-?(TGF-?)were determined in serum by ELISA.Compared to the Control group,IL-6 and TGF-? of the Model group both increased significantly(p<0.001).All the groups with three doses of PCT showed improved effect for decreasing of inflammatory factors.To summarize,PCT showed obviously preventive effect on peritoneal adhesion of rat.
Keywords/Search Tags:Adhesion, PEG-CNP-TR, Postoperative surgery adhesion, Antiinflammation, Antioxidationy
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