The Effects Of Dual Antiplatelet On Platelet Function In Sepsis Rats And Acute Kidney Injury

Objective:To observe the effects of aspirin and clopidogrel dual antiplatelet on platelet function in sepsis rats and acute kedney injury.Methods:In a modeal of rats in which LPS was injected intraperitoneallly,40 male Wistar rats were randomly divided into five groups (8 rats in each group) control group (group N), endotoxin group (group LPS), aspirin group (group A), clopidogrel group (group C), aspirin plus clopidogrel group (group; A+C). The rats in N group, LPS group, were respectively treated with normal saline 1ml while A group, C group, A+C group, were respectively given aspirin (100mg/kg), clopiogrel (200mg/kg), aspirin (100mg/kg)+clopiogrel (200mg/kg) pretreatment by gavage for three days. Then normal saline was injected in control group (10ml/kg) by intrapertoneal, rats in all the tested groups were administered with LPS (10mg/kg) by the same way. At 6h after septic rats had been induced, each groups were executed and their renal tissue and serum were collected respectively to detect Cys C, blood urea nitrogen, serum creatinine. The expression level of platelet CD62P and TLR4 were measured by flow cytometry instrument, the concentration of TNF-a and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA), platelet aggregation was assayed by the whole blood electrical impedance aggregometry, the change of renal pathology was scored by light microscope.Results:1. The pathological changes in renal tissue observed by light microscope: The structure of renal glomerulus and the renal tubule were normal in N group. In LPS group, the renal glomerulus were shrinked obviously. The renal tubule epithelial cells degeneration, necrosis ablate could be found. The blood stasis of capillary, tube formation, and severely inflammatory cell infiltrated in renal interstitium. Compared with LPS group, the changes of renal glomerulus and renal tubule were smaller in A group, C group and A+C group. And the lightest pathological change was occurred in A+C group.2.The general state of rats in this experiment:There were no significantly changes in the N group. After LPS (1mg/kg) was injected into experimental animal (LPS group) through the vein, fever, tachypnea and tachycardia emerged. Rats in LPS group loss of appetite, listlessness, stimulate poor response. Compared with LPS group, the symptoms has relieved significantly in A group, C group and A+C group.3.The levels of Cys C, SCr, BUN and kidney W/D in each group: Compared with N group, the serum content of Cys C, SCr, BUN and kidney W/D were markedly elevated in LPS group at 6 hours points (P<0.05), which were significantly lower in A group, C group and A+C group contrast with that in LPS group (P<0.05).4.The changes of platelet aggregation, CD62p, TLR4 and the levels of TNF-a and IL-6:Results compared with those in N group, The expression of platelet aggregation, CD62p, TLR4 and the levels of TNF-a and IL-6 in LPS group were markedly increased (P<0.05), which were significantly lower in A group, C group and A+C group contrast with that in LPS group (P<0.05).The most obvious change was occurred in A+C group.Conclusion:Aspirin and clopidogrel can block the platelet activation pathway and inhibit the levels of TNF-a and IL-6 in serum, thus modify the inflammatory response and provide synergetic effects against acute kidney injury induced by sepsis.