辛伐他汀对脓毒性休克大鼠中性粒细胞uPA/PAI-1表达的影响  

Effects of simvastatin on expressions of uPA/PAI-1 in neutrophils in rats with septic shock

作　　者：武晓灵[1] 喻莉[1] 龙鼎[1] 达兴文 明章银[2] 

机构地区：[1]武汉市中心医院重症医学科,430014 [2]华中科技大学同济医学院基础医学院药理学院,430000

出　　处：《实用医学杂志》2016年第4期519-522,共4页The Journal of Practical Medicine

基　　金：湖北省武汉市科技局关键技术攻关计划项目(编号:2013060602010252)

摘　　要：目的:探讨辛伐他汀对脓毒性休克大鼠中性粒细胞uPA/PAI-1表达的影响。方法:SD大鼠随机分为正常对照组、内毒素组、辛伐他汀组,记录整个过程中左心室压力的变化。注射内毒素90min后,从下腔静脉收集全血,并分离出中性粒细胞,以检测尿激酶型纤溶酶原激活物(uPA)和纤溶酶原激活物抑制剂-1(PAI-1)的水平。结果:注入内毒素后,左心室收缩压(LVSP)、左室压力最大上升速率(+dp/dtmax)和心率均显著降低。而辛伐他汀则可以阻止LVSP、+dp/dtmax和心率的下降,但不影响左心室舒张末压(LVEDP)。内毒素可引起中性粒细胞uPA含量的显著下降和PAI-1含量的上升,而辛伐他汀可减弱内毒素对中性粒细胞的上述影响。结论:辛伐他汀对于内毒素诱导的脓毒性休克的心脏功能具有保护作用,并且可以调控中性粒细胞uPA和PAI-1的表达。Objective To explore the effects of simvastatin on the protein expressions of urokinase- typeplasminogen activator （uPA） and plasminogen activator inhibitor-1 （PAI-1）. Methods Male Sprague - Dawley rats were divided into saline group, LPS group and LPS plus simvastatin group, and were then pretreated with simvastatin （1 mg/kg） for 30 minutes before addition of LPS （8 mg/kg）. Changes in left ventricular pressure were recorded. Ninety minutes after LPS injection, whole blood was collected from the inferior vena cava, and neutrophils were separated. The neutrophils were then lysed to detect levels of uPA and PAI-1. Results Left ventricular systolic pressure （LVSP： mmHg）, maximal differential of left ventricular pressure （＋dp/dtmax：mmHg/s）, and heart rate （beats/min） were markedly decreased at different time points after administration of LPS, and maximal differential of left ventricular pressure increased in the rats receiving LPS as compared with those receiving saline, although the differences between the control and LPS groups were not statistically significant. LPS caused a great decline in uPA content and an elevation in PAI-1 content in neutrophils, but simvastatin diminished the impact of LPS on neutrophils. Conclusion Simvastatin plays a role in protection of cardiac function in rats with LPS-induced septic shock, and controls expressions of uPA and PAI- 1 in neutrophils.

关 键 词：辛伐他汀 脓毒性休克 UPA PAI-1 

分 类 号：R459.7[医药卫生—急诊医学]