PI3K-Akt信号通路及β_2-AR蛋白在外源性硫化氢后处理减轻大鼠离体心肌缺血再灌注损伤中的作用  

Exogenous hydrogen sulfide postconditioning attenuates myocardial injury in isolated rat hearts after ischemia/reperfusion via PI3K-Akt signaling pathway and modulation of β_2-AR protein

作　　者：李艳[1] 陈震[1] 

机构地区：[1]江苏省连云港市第一人民医院心功能室,222002

出　　处：《中国现代医药杂志》2014年第9期1-5,共5页Modern Medicine Journal of China

基　　金：江苏省连云港市第一人民医院青年英才豪森基金项目(编号:QN122002)

摘　　要：目的探讨外源性硫化氢后处理是否激活β2-AR受体减轻大鼠离体心肌缺血再灌注损伤。方法 70只雄性Sprague Dawley(SD)大鼠随机分为5组(n=14):缺血/再灌注组(I/R)、硫化氢后处理组(N)、溶媒组(D)、LY294002组(L)、硫化氢后处理+LY294002组(N+L)。采用离体心脏Langendorff灌注模型,各组平衡灌注20min后,停灌40min,复灌60min。记录平衡末及灌注结束时的心率(HR)、左室内压上升最大速率(+dp/dtmax)、左室内压下降最大速率(-dp/dtmax)、左室发展压(LVDP)、左室舒张末期压(LVEDP)、冠脉流量(CF);灌注结束时,心肌HE染色观察心肌组织形态;Western blot测定β2-AR、Caspase-3、p-Akt和p-ERK的表达水平。结果平衡末各组间心功能指标(基础值)差异无统计学意义(P>0.05)。复灌60min时,与I/R组相比,N组能明显改善心功能各项指标(P<0.05),使心肌组织形态有改善,β2-AR、p-Akt和p-ERK表达水平升高,而活化的Caspase-3表达水平降低(P<0.05)。LY294002逆转了硫化氢后处理改善心功能指标及升高p-Akt、pERK、β2-AR和降低Caspase-3表达水平的作用。结论外源性硫化氢后处理通过激活PI3K-Akt信号通路和调节β2-AR受体蛋白的表达,参与离体大鼠心肌缺血再灌注损伤的保护作用。Objective To investigate whether the PI3K-Akt signaling pathway and β2-AR receptor protein participate in the hydrogen sulfide postconditioning against ischemia/reperfusion injury in the isolated rat hearts. Methods 70 male Sprague Dawley （SD） rats were randomly divided into 5 groups （I/R, N, D,L,N＋L,n=14）. Hearts isolated from SD rats were mounted on a Langendorff apparatus for 20 minutes equilibration and 40 minutes global ischemia, 60min reperfusion. The heart rate （HR）, left ventricular pressure maximum increase rate （＋dp/dtmax）, left ventricular pressure drop maximum rate （-dp/dtmax）, left ventricular developed pressure （LVDP）, left ventricular end diastolic pressure （LVEDP）, coronary flow （CF） were persistently measured at the end of equilibration and perfusion. Myocardial HE staining was used to observe the morphology of myocardial tissue ; Western blot analysis was used to derermine the contents of J32-AR, Caspase-3, p-Akt and p-ERK. Results LVDP, ±dp/dtmax,,HR,LVEDP had no significant difference in group I/R,group N,group D,group L and group N＋L at the end of equili- bration （P〉0.05）, but they significantly improved in group N compared with I/R group after 60rain reperfusion （P〈0.05）. Meanwhile, the morphology of myocardial tissue was better. Compared with I/R group, N group had better hemodynamics, and the expression of p-Akt, p-ERK and J32-AR significantly increased,the expression of Caspase-3 decreased. However, LY294002 given during early reperfusion blocked the beneficial effect on hemodyamics, compared with N group, N＋L group also markedly decreased the expression of p-Akt, p-ERK and β2-AR, and increased the expression of Caspase-3 （P〈0.05）. Conclusion Exogenous hydrogen sulfide postconditioning effectively protects against ischemia/reperfusion injury on isolated rat hearts by activating PI3K-Akt signaling pathway and modulating β2-AR protein.

关 键 词：硫化氢 后处理 缺血再灌注损伤 Β-肾上腺素受体 

分 类 号：R363[医药卫生—病理学]