| Objective:(1) To observe the stimulatory of the gabexate mesilate thermo sensitivein-situ-gel.(2) To establish the animal model of severe acute panreatitis (SAP), then toanalyze the changes of the serology and histopathology.(3) To assess the therapeutic effectof injectable gabexate mesilate thermo sensitive in-situ-gel on the treatment of SAP.Material and methods:(1) Nine male SD rats were involved in the test according to theself-bilateral confrontation method. The gabexate mesilate thermo sensitive in-situ-gel wasinjected into right hindlimb of rats, physiological saline was injected into left hindlimb ofrats. Animals were killed at3,24and48h after injection. The changes of histopathologyof muscular tissue were observed.(2) Forty-eight male SD rats were randomly divided intosham operation (SO) group and SAP group. The model of SAP was induced by retrogradeinjection of3.5%sodium taurocholate into the bile-pancreatic duct. Rats were killed at1,6and12h after sodium taurocholate injection. The humid weigh of pancreas, ascites,changes of histopathology of pancreatic tissue and serum inflammatory factors wereobserved.(3) Forty male SD rats were randomized into sham operation (SO) group（n=8）,SAP group（n=8）, systemic administration group（n=12） and therapeutic alliance group（n=12）. The model of SAP was induced by retrograde injection of3.5%sodiumtaurocholate into the bile-pancreatic duct. The gabexate mesilate was injected via caudalvein of rats in systemic administration group. In therapeutic alliance group, not only theinjectable gabexate mesilate thermo sensitive in-situ-gel was injected into the surfaces ofpancreas but also the gabexate mesilate was injected via caudal vein of rats. Rats werekilled at12h after the treatment. The humid weigh of pancreatic tissue, ascites, andchanges of histopathology of pancreatic tissue, serum inflammatory factors and apoptoticindex were observed. Results:(1) After the injection of gabexate mesilate thermo sensitive in-situ-gel, therewere no hyperemia, hemorrhage and swelling in muscle tissues.(2) All Forty-eight ratswere modeling successed, achievement ratio is100%. At the same time points, changes ofpancreatic humid weigh, ascites, histopathological score and levels of amylase (AMY),TNF-α and IL-6were significantly increased, compared with SO groups (SO group vs.SAP group, P<0.05). All index were increased in SAP groups (SAP1h group vs. SAP6hgroup vs. SAP12h group, P<0.05).(3) The death rate of systemic administration groupand therapeutic alliance group is16.7%（2/12）, respectively. Compared with the SAPgroup, the pancreatic humid weigh, ascites, histopathological score, levels of TNF-α andIL-6were decreased in systemic administration group and therapeutic alliance group（P＜0.05）. Compared with the systemic administration group, the levels of TNF-α and IL-6,histopathological score were decreased in therapeutic alliance group（P＜0.05）, but therewere no significant difference of pancreatic humid weigh, ascites, levels of AMY andapoptotic index between the therapeutic alliance group and systemic administration group（P＞0.05）.Conclusion:(1) The gabexate mesilate thermo sensitive in-situ-gel is non-stimulatory.(2)The method of preparing the model of SAP is successful, stable and well repeatable.(3)The combination of gabexate mesilate thermo sensitive in-situ-gel and systemicadministration is effective in the treatment of SAP. |
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