Protective Effect Of Lipo-prostaglandin E₁on Renal Damage Induced By Experimental Severe Acute Pancreatitis

ObjectivesTo evaluate the protective effect of Lipo-prostaglandin E₁against kidney injury induced bysevere acute pancreatitis in rats and to investigate its mechanism by observing the dynamicchanges of PGI₂，TXA₂，TXA₂/PGI₂and TNF-α in serum.MethodsA total of90healthy Sprague-Dawley （SD） rats were randomly divided into five groups:the sham operation group （SO）, severe acute pancreatitis group （SAP group） and Lipo-PGE₁treatment of low-dose group （PG1group）, medium dose group（PG2group）, high dose group（PG3group）, each group18. SAP was induced by retrograde injection of3.5%sodiumtaurocholate into bile duct at dose of1ml/kg of the body weight. On the basis of the SAP modelgroup, Lipo-PG E₁low, medium and high dose groups was intraperitoneally injected inrespective doses of5μg/kg,10μg/kg,20μg/kg; SO group was injected with the same volume ofsodium chloride solution after being flipped the duodenum and pancreas gently, each groupwere hypodermically injected saline solution in dose of30ml/kg after operation.The rats ineach group would be opened again for observation, and sampled for testing12-24hours afterthe operation. Testing indicators:1. serum amylase（AMY）;2.serum creatinine（SCR）;3. serumurea nitrogen（BUN）;4.serum prostaglandin I₂（PGI₂）;5. serum thromboxane A₂（TXA₂）6.serumtumor necrosis factor-α （TNF-α）;7. Pancreatic biopsy and pathological score;8.Kidney biopsyand pathological score. All data would be handled by SPSS13.0statistical software.ResultsThere were no significant changes of all parameters at all time point in the SO group（P>0.05）. Compared with the SO group: SAP group at both time points, the level of serumAMY,SCR,BUN,PGI₂,TXA₂and TXA₂/PGI₂and the pathology score of pancreas and kidneywas significantly increased, the difference was statistically significant （P<0.05）, the group of all time values was no statistically significant （P>0.05）. Compared with SAP group, the level ofAMY, SCR, BUN and the pathology score of pancreas and kidney in PG1group wassignificantly decreased （P<0.05）, especially the level of AMY decreased more significantly overtime, but the level of PGI₂, TXA₂,TXA₂/PGI₂and TNF-α decreased not significantly （P>0.05）;in addition to PGI₂, TXA₂in PG2group,other indicators were decreased （P<0.05）, there was nosignificant difference in two points time （P>0.05）; every indicator of PG3group decreasedsignificantly （P<0.05）, without significant difference in two points time （P>0.05）; the treatmentof PG3group was significantly （P<0.05）.Conclusions1,the model of SAP can be formed quickly after injecting into rats’ bile duct with3.5%Sodium taurocholate;2, TNF-α, PGI₂and TXA₂are key substances that response toinflammatory in SAP, the concentration disorder of them cause SAP-related kidney damage;3,Lipo-PG E₁can reduce renal damage in the SAP,the mechanism may be related with thedecrease of TNF-α on one hand, and the improvement of the microcirculation by TXA₂/PGI₂on the other hand;4, among three groups of5μg/kg,10μg/kg and20μg/kg, the treatment of20μg/kg group are the most significant.