硫化氢对离体大鼠心脏缺血/再灌注损伤的影响及机制初探  

Effect of hydrogen sulfide on myocardial ischemia/reperfusion injuryin isolated hearts of rats

作　　者：王晓燕[1] 曾翔俊[1] 郑少鹏[1] 马立权[1] 邱笑违[1] 芦玲巧[1] 王红霞[1] 张立克[1] 唐朝枢[1] 郝刚[1] 

机构地区：[1]首都医科大学病理生理学教研室,北京100069

出　　处：《中国药理学通报》2006年第12期1447-1451,共5页Chinese Pharmacological Bulletin

基　　金：北京市教育委员会基金资助项目(NoKM200510025009);北京自然科学基金资助项目(No7062007)

摘　　要：目的观察内源性CSE/H2S通路的改变以及给予H2S供体对缺血/再灌注心脏的影响,探讨该通路与心脏缺血/再灌注损伤的关系及作用机制。方法采用Langendorff离体灌流装置、通过停灌30min/复灌30min方式造成Wistar大鼠心肌缺血/再灌注损伤模型;采用外源性NaHS(40μmol.L-1)分别在停灌30min前(SIR)与停灌30min后处理(IRS)对缺血/再灌注心脏的影响。记录心脏收缩期左心室内压上升的最大变化速率(+dp/dtmax)、舒张期左心室内压下降的最大变化速率(-dp/dtmax)及左室内压差(LVP=左室收缩压-左室舒张压)。采用比色法检测灌流液中乳酸脱氢酶(LDH)、心肌MDA及SOD;采用比色法检测心肌胱硫醚-γ-裂解酶(CSE)活性;采用RT-PCR方法测定心肌组织CSEmRNA表达。结果与缺血/再灌注组(I/R)30min相比,SIR组及IRS组±dp/dtmax、LVP均增高,LDH降低;I/R组MDA水平高于对照组(CON)、SIR组及IRS组(P<0.05,P<0.01);IR组SOD活性低于SIR组及IRS组(P<0.05),但与CON组差别无显著性;I/R组大鼠心肌CSE活性低于CON组(P<0.05);而大鼠心肌CSEmRNA的表达与CON组差异无显著性。结论在缺血前后给予外源性NaHS均可改善因再灌注损伤引起的心肌收缩及舒张功能障碍;其作用机制可能是通过提高心肌SOD活性,增加氧自由基清除而拮抗缺血/再灌注引起的心功能及细胞膜损伤;心肌缺血/再灌注时内源性CSE活性抑制可能与心功能障碍及细胞损伤有关。Aim To observe changes of endogenous cystathionine-γ-lyase/Hydrogen sulfide pathway on ischemia/reperfusion injury in isolated rat hearts and to explore the relationship between this pathway and ischemia/reperfusion injury. Methods Isolated rat hearts were subjected to ischemia by stopping perfusion for 30 min followed by reperfusion for 30 min in Langendorff perfusion system. Using exogenous hydrogen sulfide, hearts were preconditioned 20 min before stopping perfusion and postconditioned 30 min after reperfusion respectively. Hearts were divided into four groups： Group CON, persistently perfused with KH fluid without myocardial ischemia/reperfusion; group IR, treated as above ischemia/reperfusion method; group SIR, preconditioned with NariS; group IRS, postconditioned with NariS. The computer-based electrophysiological recorder system was used to measure changes of maximal rate of the pressure increase in contract phase （ ＋ dp/dtmax ）, maximal rate of the pressure decrease in diastole phase of heart （ -dp/ dtamax ） and difference of left ventricular pressure （LVP）. Colorimetry method was used to assay the lactate dehydrogenase （LDH） in effluent, cystathionine-β-synthase （ CSE ）, malondialdehyde （ MDA ） and superoxide dismutase （SOD） activities of myocardial tissues. RT-PCR method was used to test CSE mRNA expression in myocardial tissues. Results Compared with group I/R, values of ± dp/dtmax and LVP were increased, and LDH content was decreased in groups SIR and IRS in reperfusion for 30 min. The content of MDA in group I/R was higher than that in group SIR and IRS. The activity of SOD in group IR was lower than that in group SIR and IRS （ P 〈 0. 01 ）, but there was no significant difference between group IR and CON. The activity of myocardial CSE in group IR was lower than that in group CON （ P 〈 0. 05 ） There was no significant difference of the CSE mRNA expression in myocardial tissues between group CON and IR. Conclusion The dysfunction of myocardial contraction

关 键 词：硫化氢 缺血/再灌注损伤 大鼠 胱硫醚-Γ-裂解酶 

分 类 号：R-332[医药卫生] R322.11