Therapeutic Effect Of Complement C5 Inhibitor On Renal Injury In Experimental Acute Hemorrhagic Necrotizing Pancreatitis In Rats

Objective:To assess the therapeutic effect of complement C5 inhibitor on renal injury in experimental acute pancreatitis hemorrhagic necrotizing pancreatitis(AHNP) in rats.Methods:Forty two Wistar rats were randomly divided into three groups : healthy controls (HC , n = 6) ; AP group ( n =18) ; AP-C5-I group ( n = 18) . AP was induced by retrograde infusion of 5 % sodium taurocholate into the bili-pancreatic duct in Wistar rats;AP-C5-I was injected with complemet C5 inhibitor(2.0 mg/kg) into caval vein rightly after induction of acutepancreatitis ;HC rats underwent identical surgical procedures and duct cannulation without sodium taurocholate.Both AP and AP-C5-I group were sacrificed at 6h, 12h and 18h after the operation and either group was 6 rats at each time.The serum levels of BUN, Cr,IL-1βand C5a of each group were tested.The myeloperoxidase (MPO) of kidney tissue were evaluated. The expression of C5,IL-1β,TNF-αand IL-10mRNA in kidney was measured with realtime reverse transcription-polymerase chain reaction technique. The pathological changes of kidney were observed and the pancreatic pathomor -phological score was also determined.Results:The serum levels of BUN , creatinine, IL-1βand C5a in AP group increased significantly ( P < 0. 01 vs HC) , which decreased significantly in AP-C5-I group ( P < 0. 01 vs AP) .Intrarenal expressions of C5,IL-1β,TNF-αand IL-10mRNA could be observed in HC ,but C5 and IL-1βmRNA expression were weak in HC .the Intrarenal expressions of MPO of kidney tissue, the level of IL-1β,TNF-αmRNA in kidney and the pancreas and kidney pathomorphological score were elevated after operation. Such parameters of AP group were higher than those of HC group at any observed time significantly (p 0.05), and such parameters of AP-C5-I group were higher than those of HC group, but still low compared with those of AP group significantly (p 0.05), whereas C5 mRNA expression had no significant differences between AP group and AP-C5-I group ( P > 0. 05) . C5 inhibition had no effect on the severity of renal tissue damage.The levels of IL-10 mRNA in kidney tissue increase firstly and decrese lately after operation, and the levels of AP group and AP-C5-I group were higher than those of HC group (p 0.05),and which at 6h and 12h after operation of AP-C5-I group were higher than of AP group significantily (p 0.05).Conclusion:(1)The model of retrograde injected 5% sodium taueocholate into choledochopancreatic duct to induce AHNP with renal injury experimental was valuable and simplified duplicated. (2)The elevated serum IL-10 and abnormal expression of IL-1β,TNF-αand IL-10 mRNA could make the inflammation incontrollable, and they were involved in the initiation and development of renal injury associated with AHNP in rats. (3)In AHNP-induced renal injury in rats, the balance of proinflammatory and anti-inflammatory cytokines was disturbed, which could cause uncontrolled inflammation .(4)The abnormal activation of the complement system could play a pivotal role in the the imbalance of proinflammatory and anti-inflammatory cytokines ,which contributed to the renal injury in AHNP.(5)Complement C5 Inhibitor could block the activation of complement system and partly attenuate renal injury in AHNP and the regulated effects of Complement C5 Inhibitor on inflammatory mediators could improve renal functions effectively.