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Experimental Sduty Of The Protective Effects Of Rosiglitazone On Acute Necrotic Pancreatitis(ANP)and ANP-associated Lung Injury

Posted on:2011-08-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:D X CaiFull Text:PDF
GTID:1484303311463444Subject:Digestive science
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Part one Experimental study of the protective effects of rosiglitazone onacute necrotic pancreatitisObjective To investigate the protective effects and mechanisms of Rosiglitazone on acute necrotic pancreatitis (ANP).Methods seventy‐two SD rats were randomized into three groups: sham operation (SO)group, ANP group and rosiglitazone‐pretreated group. The model of ANP was induced by retrograde injection of 5% sodium taurocholate into the bili‐pancreatic duct in SD rats, rosiglitazone‐pretreated group were given 10mg/kg rosiglitazone intraperitoneally 30 min before inducing ANP. Rats in the three groups were killed at 3,6,12 hours after induction of the model. The levels of amylase in plasm, the myeloperoxidase(MPO) in the pancreas were measured. The levels of plasm TNF‐α,IL‐6 were detected by enzyme linked immunosorbent assay(ELISA).The expressions of NF‐κB in pancreatic tissue were assayed by immunohistochemistry,the expressions of PPARγmRNA and HSP‐70mRNA in pancreatic tissue was detected by reverse transcript PCR(RT‐PCR).The histopathological changes and the histologic scores of pancreatic tissue were evaluated.Results (1)Compared with SO group, the levels of plasm amylase,TNF‐α,IL‐6, and the intrapancreatic MPO significantly increased in ANP group(P<0.05), the expression of NF‐κB in pancreatic tissue significantly increased in ANP group(P<0.01), the histologic scores of pancreatic tissue significantly increased in ANP group(P<0.01),the pancreas injury were aggravated gradually. (2)Compared with ANP group, the levels of plasm amylase,TNF‐α, IL‐6 ,intrapancreatic MPO, and the expression of NF‐κB in pancreatic tissue significantly decreased in rosiglitazone‐pretreated group(P<0.05), the expressions of PPARγmRNA and HSP‐70mRNA in pancreatic tissue significantly increased in rosiglitazone‐pretreated group ( P<0.05 ) , the pancreatic histopathologic scores significantly decreased in rosiglitazone‐pretreated group at 6h,12h(P<0.05), the severity of pancreas injury also significantly decreased in rosiglitazone‐pretreated group.Conclusions rosiglitazone might have protective effects on ANP by activing PPARγ, inducing HSP‐70 and inhibiting NF‐κB in the pancreas, and decreasing the production of TNF‐α,IL‐6.Part tow Experimental study of the protective effects of rosiglitazone onacute necrotic pancreatitis‐associated lung injuryObjective To investigate the protective effects and mechanisms of rosiglitazone on acute necrotic pancreatitis‐associated lung injuryMethods seventy‐two SD rats were randomized into three groups: sham operation (SO)group, ANP group and rosiglitazone‐pretreated group. The model of ANP was induced by retrograde injection of 5% sodium taurocholate into the bili‐pancreatic duct in SD rats, rosiglitazone‐pretreated group were given 10mg/kg rosiglitazone intraperitoneally 30 min before inducing ANP. Rats in the three groups were killed at 3,6,12 hours after induction of the model. The levels of PaO2, the intrapulmonary MPO , and the wet /dry ratio of lung were measured. The expressions of NF‐κB in pulmonary tissue were assayed by immunohistochemistry, the expressions of TNF‐αmRNA and ICAM‐1 mRNA in pulmonary tissue was detected by reverse transcript PCR(RT‐PCR). The histopathological changes of pulmonary tissue were evaluated.Results (1)Compared with SO group, the levels of PaO2 decreased in ANP group(P<0.05), the intrapulmonary MPO significantly increased in ANP group(P<0.05), the expression of NF‐κB , TNF‐αmRNA and ICAM‐1 mRNA in the lung significantly increased in ANP group(P<0.01), and the wet /dry ratio of lung also significantly increased in ANP group at 6h,12h(P<0.01), the lung injury were aggravated gradually. (2)Compared with ANP group, the levels of PaO2 increased in rosiglitazone‐pretreated group(P<0.05),the levels of intrapulmonary MPO, the expression of TNF‐αmRNA and ICAM‐1 mRNA in the lung significantly decreased in rosiglitazone‐pretreated group (P<0.05), the expression of NF‐κB in pulmonary tissue significantly decreased in rosiglitazone‐pretreated group(P<0.05), the wet /dry ratio of lung significantly decreased in rosiglitazone‐pretreated group at 6h,12h(P<0.05), the severity of lung injury also significantly decreased in rosiglitazone‐pretreated group.Conclusions Rosiglitazone might have protective effects on lung injury associated with ANP by inhibiting NF‐κB and decreasing the production of TNF‐α,ICAM‐1.Part three Clinical study of risk factors for severe acute pancreatitiscomplicated with acute lung injury/acute respiratory distress syndromeObjective To analysis of risk factors for severe acute pancreatitis(SAP) complicated with acute lung injury/acute respiratory distress syndrome.Methods 73 case with severe acute pancreatitis were retrospective analysised from july 2007 to july 2010.they were divive into SAP complicated with acute lung injury/acute respiratory distress syndrome group(ALI/ARDS)and SAP without acute lung injury/acute respiratory distress syndrome group(ALI/ARDS). The level of serum amylase, white blood cell, blood glucose, triglyceride, calciumion,and arterial partial pressure of oxygen were measured in all pantients when they were admitted to hospital firstly. APACHEⅡscore and CT score were carried out in 24h after admission. The patients combined with infection or not were observed during admission. The difference in the all above indexes and the cause,age, gender were compared in two group.Results Compared with SAP complicated with ALI/ARDS group and SAP without ALI/ARDS group, the difference were significant in age, serum white blood cell, glucose, arterial partial pressure of oxygen ,APACHEⅡscore, CT score and infection,but there was no difference in cause. Age, serum white blood cell, blood glucose, APACHEⅡscore, CT score and infection were independent risk factors of SAP complicated with ALI/ARDS.Conclusions Age, serum white blood cell, blood glucose, APACHEⅡscore, CT score and infection were independent risk factors of SAP complicated with ALI/ARDS.
Keywords/Search Tags:Pancreatitis, rosiglitazone, PPARs, NF‐κB,HSP‐70, lung injury, NF‐κB, TNF‐α, ICAM‐1, severe acute pancreatitis, acute lung injury, acute respiratory distress syndrome, risk factor
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