蛋白酶激活受体-1拮抗剂降低心脏骤停后综合征兔血清炎性细胞因子的水平

Protease-activated receptor-1 antagonist reduces the serum levels of inflammatory cytokines in post-cardiac arrest syndrome in rabbits

目的：观察蛋白酶激活受体-1（PAR-1）拮抗剂对心脏骤停后综合征（PCAS）兔血清TNF-α、MCP-1和IL-8的影响。方法大耳白兔30只，随机分为假手术组、PCAS组、PAR-1拮抗剂组。采用窒息性心脏骤停制备兔PCAS模型。 PAR-1拮抗剂组在自主循环恢复后15 min给予PAR-1拮抗剂SCH79797（25μg／kg）静脉滴注，每天一次，其余各组给予等量生理盐水。48 h取股静脉血测定血清 ALT、cTnT、Cys -C 及 NSE，以监测器官功能的变化。采用ELISA测定血清TNF-α、MCP-1及IL-8水平。结果 PAR-1拮抗剂SCH79797可明显减轻心、脑、肝、肾功能障碍。 PCAS组血清TNF-α、MCP-1和IL-8水平均明显高于假手术组（ P＜0．01）。 PAR-1拮抗剂组TNF-α、MCP-1和IL-8水平均明显低于PCAS模型组（ P＜0．05）。结论 PAR-1拮抗剂SCH79797可降低PCAS兔血清TNF-α、MCP-1和IL-8水平，改善心肺复苏后多器官功能障碍。

Objective To observe the effect of protease -activated receptor -1 （ PAR -1 ） antagonist SCH79797 on the serum level of TNF -α, MCP -1 and IL -8 in post -cardiac arrest syndrome （ PCAS ） .Methods Thirty healthy male Japanese rabbits were divided into three groups randomly.They were the sham -operation group, PCAS group and PAR -1 antagonist group.The model of PCAS was established by asphyxia -induced cardiac arrest .Fifteen minutes after return of spontaneous circulation （ROSC）, SCH79797 （25 μg/kg, iv drop, q.d.） was administrated in PAR-1 antagonist group .The indicators of organ function were evaluated at 48 hours after cardiac arrest .The serum levels of TNF-α, MCP-1 and IL-8 were determined by enzyme-linked immunosorbent assay （ELISA）.Results SCH79797 alleviated the dysfunction significantly in heart , brain, liver and kidney .Compared with the sham -operation group , the serum levels of TNF-α, MCP-1 and IL-8 were increased significantly in PCAS group （P〈0.01）.Compared with the PCAS group, the serum levels of TNF-α, MCP -1 and IL -8 were decreased significantly in PCAS group （ P 〈0.05 ）. Conclusion SCH79797 can reduce the serum levels of TNF -α, MCP-1 and IL-8 in post-cardiac arrest syndrome in rabbits , and attenuate multiple organ dysfunction after cardiopulmonary resuscitation .