脓毒症时各型一氧化氮合酶在大鼠心脏中的表达及其可能机制

Expression pattern of nitric oxide synthases in heart of septic rat and its mechanism

摘要:

目的研究脓毒症时各型一氧化氮合酶(NOS)在心脏中的损伤作用及其机制。方法成年雄性Wistar大鼠腹腔注射脂多糖(LPS)制备脓毒症模型。应用多导生理仪监测大鼠心功能变化;用分光光度计法测定大鼠心肌组织NOS的活性;用RT-PCR和Western blot对大鼠心肌组织各型NOS的表达进行半定量分析。结果给予LPS后6h大鼠心肌收缩和舒张功能受损下降,心肌中iNOS的活性明显升高,eNOS和nNOS(合称cNOS)活性减弱;RT-PCR和Western blot结果显示,给予LPS后cNOS的表达减少,给予LPS后iNOS表达量明显增加。结论脓毒症时,iNOS、nNOS和eNOS的表达和活性发生改变;心肌细胞上iNOS表达及活性升高,这些变化可能在心功能降低中发挥作用。

Abstract:

Objective To define the roles of three types of nitric oxide synthases (NOS) in heart injury of septic rat and its relevant mechanism.Methods Male Wistar rats received intraperitoneal injection of lipopolysaccharide(LPS) to prepare septic rat models.Cardiac function was recorded on a computer with an analogic/digital transducer.The activities of NOS were analyzed by spectrophotometer.The expressions of three types of NOS in rat hearts were assessed by semi-quantitative RT-PCR and Western blot.Results At 6 hours after LPS injection,the cardiac systolic and diastolic function were impaired;the activities of inducible NOS (iNOS) were increased;the activities of constitutive NOS (cNOS) endothelial NOS (eNOS) and neuronal NOS (nNOS) were decreased;RT-PCR and Western blot showed that expressions of including cNOS were markedly down-regulated,but iNOS expressions were increased significantly after LPS administration.Conclusion The expressions and activities of iNOS,nNOS,and eNOS change in case of sepsis.Increase in iNOS expression and activity in cardiomyocytes may contribute to the progression of heart failure after LPS injection.?更多