疲劳应激对血管内皮功能障碍大鼠脂蛋白相关磷脂酶A2含量和4型G蛋白耦联受体表达的影响及通络干预的作用  

The expressions of lp-PLA2 and GPR4 in vessel endothelial dysfunction rats induced by fatigue stress and the effect of Tongluo intervention

作　　者：韩建科[1,2,3] 魏聪[1,2,3] 贾振华[1,2,4,3] 常丽萍[1,3] 王宏涛 张彦芬 

机构地区：[1]河北以岭医药研究院,河北石家庄050035 [2]国家中医药管理局重点研究室 [3]河北医科大学附属以岭医院 [4]河北省络病重点实验室

出　　处：《中国老年学杂志》2012年第11期2294-2297,共4页Chinese Journal of Gerontology

基　　金：国家重点基础研究发展计划(973计划)项目(No.2005CB523301);国家十一五"重大新药创制项目":(No.2009ZX09313-003)

摘　　要：目的方法探讨通络干预对疲劳应激致内皮功能障碍大鼠血清脂蛋白相关磷脂酶A2(lp-PLA2)水平和主动脉4型G蛋白耦联受体(GPR4)表达的影响。方法将60只雄性Wistar大鼠随机分为正常对照组、疲劳应激组、人参组和通心络组。采用"基础饮食+负重力竭游泳"方法建立疲劳应激模型。通过游泳时间、爬杆时间评价模型建立,扫描电镜观察血管内皮形态,并检测一氧化氮(NO)、内皮素(ET)评价内皮功能;应用ELISA方法检测血清lp-PLA2水平,应用Real Time PCR和Western印迹分析检测主动脉GPR4 mRNA、蛋白表达水平。结果疲劳应激组血管内皮结构损伤,内皮分泌NO明显减少,ET明显增加(均P<0.05)。疲劳应激组血清lp-PLA2水平显著升高(P<0.01),主动脉GPR4 mRNA和蛋白表达水平明显高于正常对照组(P<0.05)。人参、通心络干预后,血清NO水平明显增加,血浆ET含量明显降低(均P<0.01);血清lp-PLA2水平明显下降(均P<0.01),主动脉GPR4表达水平显著下降(均P<0.05)。结论疲劳应激模型大鼠血管内皮出现明显损伤,血清lp-PLA2含量明显增加,主动脉GPR4 mRNA和蛋白表达水平明显升高。通络治疗能显著降低疲劳应激大鼠血清lp-PLA2水平,抑制主动脉GPR4 mRNA和蛋白表达,因此通络治疗可有效抑制ox-LDL对血管内皮的损伤。Objective To observe the expressions of lp-PLA2 and G protein-coupled receptor 4 （GPR4） in vessel endothelial dysfunction rats induced by fatigue stress and to discuss the effect of Tongluo intervention. Methods 60 male Wistar rats were randomly divid- ed into normal control, fatigue stress, Renshen and tongxinluo groups. Fatigue stress rats models was established by basic diet ＋ weight- bearing and exhaustive swimming method. Swimming time, climbing pole time were used to evaluate model, scaning electron microscopy was used to observe the shape of vascular endothelial cells, and of the expressions of NO, ET were tested, the serum level of lp-PLA2 was detec- ted by ELISA, GPR4 mRNA and protein expressions were measured by Real Time PCR and Western blot. Results In model group, vascu- lar endothelial smlctural was damaged, the expression of NO was decreased, the expression of ET was increased significantly （all P 〈 0. 05 ）. In fatigue stress group, the serum level of lp-PLA2 was significantly higher （P 〈0. 01 ） ; GPR4 mRNA and protein levels in aortic were sig- nificantly higher than those of normal control group （ P 〈 0. 05 ） , in Renshen and Tongxinluo group, the levels of plasma NO were significant- ly increased, the levels of plasma ET were decreased significantly （all P 〈 0. 01 ） ; the levels of serum Ip-PLA2 were significantly decreased （ all P 〈 0. 01 ）, the expressions of GPR4 in aortic were significantly decreased （ all P 〈 0. 05 ）. Conclusions Tongluo treatment can signifi- cantly reduce the level of serum lp-PLA2 of fatigue stress rats, inhibit GPR4 mRNA and protein expressions. For this reason, Tongluo treat- ment can effectively inhibit ox-LDL on vascular endothelial damage.

关 键 词：疲劳应激 人参 通心络 lp-PLA2、GPR4 

分 类 号：R28[医药卫生—中药学]