磷脂酶A_2抑制剂对家兔内毒素休克血中血小板活化因子活性的调节作用观察

Effects of phospholipase A_2 inhibitors on the activity of platelet-activa ting factor in rabbits with endotoxic shock

通过家兔内毒素休克模型重点观察了磷脂酶Ａ２（ＰＬＡ２）抑制剂磷酸氯喹和地塞米松对血中ＰＬＡ２及其相关脂介质的影响。实验分成４组：（１）假手术组（ＳＯ）；（２）内毒素休克组（ＥＳ）；（３）磷酸氯喹预处理组（ＣＱ）；（４）地塞米松预处理组（ＤＸＭ）．分别于给药前、内毒素或生理盐水注射后５、３０ｍｉｎ，１、３、５、８ｈ取血测ＰＬＡ２血小板活化因子（ＰＡＦ）、ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１ａ，同时连续监测平均动脉压（ＭＡＰ）、心率和呼吸，观察动物８ｈ存活率、ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１ａ浓度均明显升高，ＰＬＡ２抑制剂能显著抑制ＰＬＡ２及ＰＡＦ活性，其中磷酸氯喹对ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１ａ的抑制最为显著。此外，ＰＬＡ２抑制剂可使家兔８ｈ存活率由４８％提高到７５％（ＣＱ组）和７０％（ＤＸＭ组）。提示，用ＰＬＡ２的抑制剂磷酸氯喹和地塞米松均能显著抑制内毒素休克时ＰＬＡ_２的活性及相关脂介质如ＰＡＦ、ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１ａ的升高，提高动物存活率，有效地改善休克动物的预后。

The effects of chloroquine and dexamethasone,inhibitors to phospholipase A2(PLA2),on the activity of blood PLA2 and its related lipid mediators were observed in rabbits with endotoxic shock.The rabbits were randomized into control group with sham operation(So,n=12),endotoxic shock group(ES,n=31),chloroquine(3mg/kg)-pretreated group(CQ,n=16)and dexamethasone(5mg/kg)pretreated group(DXM,n=10).Blood samples were obtained before and 5 min,30 min,1h,3h.5h and 8 h after the initiation of endotoxic shock and PLA2, platelet-activating factor (PAF),TXB2/6-keto-PGF(1a)were determined and changes of mean arterial pressure(MAP)and respiratory rate(RR)were recorded.It was found that the activity of PLA2,PAF and TXB2/6-keto-PGF1a were markedly increased after the inusion of endotoxin and CQ and DXM markedly inhibited the activities of PLA2 and PAF.The inhibitory effects of CQ on TXB2/6-keto-PGF1a seemed to be more efficient.In addition,the survival time was increased to 75%in CQ group and to 70% in DXM group.The findings suggest that CQ and DXM,inhibitors to PLA2,can significantly suppress the activity of PLA2 and decrease the elevation of the related lipid mediators such as PAF and TXB2/6-keto PGF1a.Consequentl the prognosis of the animals with endotoxic shock is improved and the survival rate increased.