硫化氢抑制大鼠急性心肌缺血引起的细胞炎症反应  

Hydrogen sulfide inhibits inflammatory responses induced by acute myocardial ischemia in isolated rat hearts

作　　者：谢英花[1] 马燕山[2] 张楠[3] 张建新[3] 

机构地区：[1]河北科技大学药学系,河北石家庄050018 [2]石家庄市中医院放射科,河北石家庄050051 [3]河北省医学科学院,河北石家庄050021

出　　处：《中国病理生理杂志》2014年第9期1698-1702,共5页Chinese Journal of Pathophysiology

基　　金：河北省自然科学基金资助项目(No.C2009001458);河北省应用基础研究计划重点基础研究项目(No.13967602D)

摘　　要：目的:探讨硫化氢(H2S)能否抑制大鼠急性心肌缺血引起的细胞炎症反应。方法:结扎大鼠左冠状动脉前降支4 h,引起心肌缺血损伤。健康雄性SD大鼠随机分为假手术组(sham)、缺血组(ischemia)以及硫氢化钠(NaHS)5μmol/L、10μmol/L和20μmol/L组。NaHS组分别于心肌急性缺血2 h时更换为5μmol/L、10μmol/L和20μmol/L NaHS灌流液。缺血后4 h记录心功能变化。实时荧光定量PCR检测离体心肌组织中TNF-α、IL-1β、IL-6、IL-10和ICAM-1 mRNA表达;Western blotting检测离体心肌组织中NF-κB的表达。结果:Ischemia组离体心肌功能下降(与sham组相比P<0.01),NaHS组离体心肌功能比ischemia组明显改善(P<0.05或P<0.01)。Ischemia组离体心肌组织中TNF-α、IL-1β、IL-6和ICAM-1 mRNA表达显著增强,IL-10 mRNA表达显著降低(与sham组相比P<0.01);NaHS组离体心肌组织中TNF-α、IL-1β、IL-6和ICAM-1 mRNA表达比ischemia组明显降低,NaHS 10μmol/L,20μmol/L组离体心肌组织中IL-10 mRNA表达比ischemia组明显升高(P<0.05或P<0.01)。与sham组相比,ischemia组NF-κB表达显著增加(P<0.01),而NaHS 10μmol/L和20μmol/L组NF-κB的表达明显低于ischemia组(P<0.05或P<0.01)。结论:H2S可通过阻断NF-κB相关信号通路的转导,抑制炎症反应,明显改善大鼠急性心肌缺血损伤。AIM： To investigate whether hydrogen sulfide（ H2S） protects the hearts against inflammatory responses induced by acute myocardial ischemia in isolated rat hearts. METHODS： Rat acute myocardial ischemia injury was induced by ligation of the left anterior descending coronary artery for 4 h,and the normal perfusate was replaced with NaHS（ 5 μmol /L,10 μmol /L and 20 μmol /L） perfusate accordingly in NaHS groups 2 h after ischemia. The changes of cardiac function in the myocardial ischemic injury rats were observed. The mRNA expression of TNF-α,IL-1β,IL-6,IL-10 and ICAM-1 was detected by real-time PCR. The protein level of nuclear factor-κB（ NF-κB） in the myocardial tissues was detected by Western blotting. RESULTS： The cardiac function in ischemia group was lower than that in sham group（ P〈 0.01）. Compared with ischemia group,perfusion of NaHS resulted in the improvement of the cardiac function（ P 〈0. 05 or P〈 0. 01）. Compared with sham group,the mRNA expression of TNF-α,IL-1β,IL-6 and ICAM-1 in the cardiac tissues was significantly increased,and the mRNA expression of IL-10 in the cardiac tissues was significantly decreased in ischemia group（ P〈 0. 01）. Compared with ischemia group,the perfusion of NaHS significantly decreased the mRNA expression of TNF-α,IL-1β,IL-6 and ICAM-1（ P 〈0. 05 or P 〈0. 01）. The perfusion of NaHS at concentrations of 10μmol/L and 20 μmol/L significantly increased the mRNA expression of IL-10（ P 〈0. 01）. The protein level of NF-κB in ischemia group was markedly higher than that in sham group（ P〈 0. 01）. Compared with ischemia group,the perfusion of NaHS at concentrations of 10 μmol /L and 20 μmol /L significantly decreased the expression of NF-κB（ P〈 0. 05 or P 〈0. 01）. CONCLUSION： H2 S protects the hearts against acute ischemia injury through inhibition of NF-κB activation and subsequent down-regulation of NF-κB-dependent inflammatory gene expression.

关 键 词：硫化氢 急性心肌缺血 大鼠 心脏 NF-ΚB 炎症 

分 类 号：R363[医药卫生—病理学]