Protective effects and mechanism of aspirin combined with clopidogrel on acute kidney injury induced by sepsis

doi:10.3969/j.issn.1002-1949.2015.11.002

Abstract：Objective To investigate the possible protective effects of aspirin combined clopidogrel on acute kidney injury in rats with sepsis , and its possible mechanism .Methods Forty male Wistar rats were randomly divided into five groups: control group ( group N) , endotoxin group ( group LPS ) , aspirin group ( group A ) , clopidogrel group ( group C ) , aspirin plus clopidogrel group ( group A+C) , with 8 rats in each group .The rats in group N and group LPS were respectively treated with 1 mL normal saline, while the rats in groups A, C and A+Cwere respectively given aspirin (100 mg/kg), clopiogrel (200 mg/kg), aspirin (100 mg/kg) +clopidogrel (200 mg/kg) pretreatment by gavage for three days.Then normal saline was injected in control group (10 mL/kg) by intrapertoneal, rats in all the tested groups were administered with LPS (10 mg/kg) by the same way.The blood Cr, BUN, Cys C, TNF -α, IL-6 and the expression level of platelet CD 62p, TLR4, rate of platelet aggregation 6 h after LPS or saline injection were determined .At last, kidney wet/dry weight ratio ( W/D), pathological changes in the kidney were observed by hematoxylin eosin (HE) staining.Results Compared with LPS model group , renal function , the level of Cys C , TNF-αand IL-6 in serum, the expression of platelet aggregation , platelet CD62p, TLR4 and kidney W/D ratio, significantly decreased in drug intervention groups .The histological changes also lessened , especially in drug combination group.Conclusion Aspirin and clopidogrel can block the platelet activation pathway and inhibit the levels of TNF-αand IL-6 in serum, thus modify the inflammatory response and provide synergetic effects against acute kidney injury induced by sepsis .