P2 Y12受体拮抗剂对脓毒症大鼠血小板功能和急性肾损伤影响的实验研究

目的：观察血小板P2Y12受体拮抗剂氯吡格雷对脓毒症大鼠血小板功能和急性肾损伤（AKI）的影响。方法36只雄性Wistar大鼠随机分为正常对照组（NC组）、急性肾损伤组（AKI组）、氯吡格雷组（CL组），每组12只。AKI组、CL组分别腹腔注射内毒素（LPS）10 mg·kg－1建模；CL组在LPS注射后立即给予氯吡格雷800 mg·kg－1灌胃；建模后3 h，测定各组血小板CD62P的阳性表达水平及血小板聚集率，并检测血肌酐、尿素氮、TNF-α和IL-6的水平，取肾组织HE染色进行病理组织学观察。结果 AKI组血小板CD62P的表达水平明显高于NC组（P＜0．05），而CL组则明显低于AKI组（P＜0．05）。AKI组血小板聚集率明显高于NC组，CL组血小板聚集率较AKI组明显降低且低于NC组（P＜0．05）。AKI组、CL组大鼠血清TNF-α和IL-6、血肌酐、尿素氮水平均高于NC组（P＜0．05），而CL组上述指标均明显低于AKI组（P＜0．05）。AKI组大鼠肾组织病理损伤显著，CL组肾损伤程度较AKI组明显减轻。结论血小板参与AKI的发病机制，血小板P2Y12受体拮抗剂氯吡格雷可减轻内毒素诱导的肾组织的损伤，改善肾功能，其机制可能与抑制脓毒症大鼠血小板的过度活化和聚集，下调炎症因子的表达有关。

Effects of P2 Y12 receptor antagonist on platelet function in sepsis and acute kidney injury

Objective To observe the effects of P2Y12 receptor antagonist of clopidogrel on platelet function in sepsis and inflammato-ry reaction of kidney tissues in acute kidney injury.Methods Thirty-six male Wistar rats were randomized into 3 groups:normal con-trol group (NC),acute kidney injury group(AKI),clopidogrel group (CL),12 rats in each group.The rats in group AKI received LPS 10 mg·kg-1 by intra-peritoneal injection to establish sepsis-AKI model;The rats in group CL were orally administered with clopidogrel at the dose of 800 mg·kg-1 immediately after injection of LPS 10 mg·kg-1 .In the 3rd hour after LPS injection ,the expression level of platelet CD62P,platelet aggregation Scr,BUN,IL-6 and TNF-αwere measured.Kidney tissues were kept for histological examina-tion.Results The expressions of platelet CD62P in AKI group and CL group were higher than that in NC group (P<0.05);The ex-pression of platelet CD62P in CL group was significantly lower than that in AKI group (P<0.05).The ratio of platelet aggregation in CL group was significantly lower than that in NC group or AKI group (P<0.05).Compared with NC group,the level of serum TNF-α, IL-6,BUN and Scr were significantly higher in AKI group and CL group (P<0.05),but those in CL group were significantly lower than that in AKI group.The obvious inflammatory reaction of kidney tissue was observed in the rats of AKI group while the less inflam-matory reaction of kidney tissue was observed in CL group.Conclusions Platelets are involved in the pathogenesis of AKI.Platelet P2Y12 receptor antagonist clopidogrel could reduce LPS-induced acute kidney injury and improve kidney function.The mechanism may be associated with inhibiting the excessive platelet activation and aggregation and downregulating the expression of inflammatory cyto-kines.