The Experimental Research Of The Effects Of The Protein Kinase D On The Acute Pancreatitis In Rats

Objective:To investigate the effects of the Protein Kinase D1on acute pancreatitis and itsmolecular mechanism.Method:Sixty six male Sprague-Dawley(SD) rats (250±30g)were equally randomized into Agroup(acute pancreatitis model group),B group(CID755673pretreatment group),Cgroup(sham operation group).A group and B group were built AP model byantidromic injected3.5%sodium taurocholate(0.1mL/100g) on the pancreatic ductwith micro-injection pump.C group’s rats were treated only by fliping the pancrease.Agroup’s rats were killed based on the time(3h,6h,9h,12h,24h).B group’s rats werekilled based on the time(3h,6h,12h).C group’s rats also were killed based on thetime(3h,6h,12h).We collected the blood serum(from the heart) to testamylase(AMS),The rest of the blood was treated for TNF-α,IL-6by ELISA.Thepancrease tissue was incised biopsy after the observision of the gross pathologicalchanges.The expresion of PKD1and Caspase-3in pancrease were detected byWestern-Blot.The expresion of NF-KB in pancreas were detected byimmunohistochemcal.Results：1.The changes of AMS,TNF-alpha,IL-6and NF-kB:In any time point,the level of theAMS,TNF-alpha,IL-6and NF-kB on C group is significantly lower than A group andB grup(P<0.05).In any time point,the level of the AMS,TNF-alpha,IL-6and NF-kBon B group is significantly lower than A group (P<0.05).2.The expression of PKD1on each groups’pancrease:In12h time point,the expressionof PKD1on C group is lower than A group and B grup(P<0.05).In12h time point,the expression of PKD1on B group is lower than A group(P<0.05).In3h-12h time pointinterval,the expression of PKD1on A group is time dependented.The expression ofPKD1rised from3h time point,and reached the peak in12h time point.The expressionof PKD1in24h time point is still high,but lower than12h time point.3.The expression of Caspase-3on each groups’pancrease:In12h time point,theexpression of Caspase-3on C group is lower than A group and B grup(P<0.05).In12htime point,the expression of Caspase-3on B group is lower than A group(P<0.05).4.The pancrease histopathological grading on each group:In any time point,the levelof the histopathological grading on C group is significantly lower than A group and Bgrup(P<0.05).In any time point,the level of the histopathological grading on B groupis significantly lower than A group (P<0.05).5.The pathological detection on each group:In any time point of C group,thepancrease acini’s structure is intact,and the interstitial is slightly edema.There is nosignificant pathological changes.In each time point of A group,the hyperemia edemaof the pancrease acinis is significant,and the gland bubble structure is disorder.Thereare some necrosis collapses in pancreatis gland bubble.The interstitial is fuzzy.Thereare many neutrophils infiltrate in the interstitial.In each time point of B group,thepathological changes is similar to the A group,but the degree is lower than A group.6.The level of apoptosis on each group:In any time point,the level of the apoptosis onC group is significantly lower than A group and B grup(P<0.05).In any time point,thelevel of the apoptosis on B group is significantly lower than A group (P<0.05).Conclution:1.PKD1is highly expressed in experimental acute pancreatitis.The expressiontendence of PKD1is time depended in3h-12h time interval.2.CID755673can effetively decrease the pancreatitis pathologicalinjury,AMY,NF-KB,TNF-alpha and IL-6,and alleviate the Inflammatory activity.3.CID755673can effetively increase the Caspase-3and apoptosis level of pancrease.