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Stage Repair With Doxycycline-eluting Stents For Colonic Anastomotic Leak In Porcine Model

Posted on:2013-01-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:J H MeiFull Text:PDF
GTID:1114330371984795Subject:Gastrointestinal Minimally Invasive Surgery
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Part1Manufacturing a doxycycline-eluting colonic anastomotic stent with PLA and PLGAObjective To manufacture a doxycycline-eluting colonic anastomotic stent.Methods With the help of institute of polymer science of Zhejiang University of techonology, the doxycycline was mixed with PLGA, which acted as a carrier, in chloroform solution. Then those mixture was spraided on a prefabricated PLA stent by electrospining. The electrospining silk was also examined by SEM-EDS.Result A noval doxycycline-eluting colonic anastomotic stent was fabricated. SEM-EDS disclosed that the electrospining silk, containing the doxycycline, had a diameter of10um.Conclusion A novel doxycycline-eluting colonic anastomotic stent was manufactured. Part2I stage repair with doxycycline-eluting stents for colonic anastomotic leak in porcine modelObjective To investigate the feasibility of I stage repair with doxycycline-eluting stents for colonic anastomotic leak in porcine model and the impact of eluting-stents on intestine barrier.Methods A total of50Bama minipigs were included to make an animal model of colonic anastomotic leak.72hours later, those porcines were randomized into3groups. They were hand-suture repair group(HS group), stent repair group(SR group) and eluting-stent group(ESR group). The animals were sacrificed on3days,7days,14days and30days after operation. The mortality and morbidity, status of anastomosis and abdominal adhesion, WBC, blood DAO and endotoxin content, the content of MDA, MPO and bursting pressure of anastomosis were determined respectively. The pathology of HE&Masson staining, a-SMA&TGF-β1immunohistochemical staining were performed. Moreover, the hydroxyproline contents and MMP-2, MMP-9mRNA expression were evaluated. The feasibility and reliability of eluting-stents for the repair of colonic anastomotic leak and impact of eluting-stents on intestine barrier were appraised respectively.Result There were2dead cases for anastomotic leak in HR group,1dead case for pneumonia in SR group and0dead case in ESR group. There was no differences in WBC, DAO, endotoxin and hydroxyproline between any2of the3groups at each harvest time(P>0.05). On7and14postoperative days, the MDA and MPO content in anastomosis of ESR and SR group was lower than that of HR group(P<0.05).On3,7,14postoperative days, the bursting pressure of ESR and SR group was higher than that of HR group(P<0.05). Especially, on3postoperative days, the bursting pressure of ESR group was a little higher than that of SR group(P<0.05). The pathology of HE&Masson staining, α-SMA&TGF-β1immunohistochemical staining showed milder inflammation, earlier collagen synthesis and mature scar formation in ESR and SR group. The expression of the mRNA of MMP-2and MMP-9in ESR group was reduced on3and7postoperative days.Conclusion I stage repair with doxycycline-eluting stents for colonic anastomotic leak in porcine model is feasible and secure. The eluting-stents can suppress the MMP expression in anastomosis and have no impact on intestine barrier.
Keywords/Search Tags:doxycycline, PLA, PLGA, biodegradable stent, drug-eluting stent, colonanastomosisdrug-eluting stent, colonic anastomotic leak, MMP-2, MMP-9, intestine barrier
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