雌二醇对大鼠缺血再灌注心肌诱生型及内皮型一氧化氮合酶活性的影响  

Effect of 17β-estradiol on myocardial inducible NOS and endothelial NOS activities after ischemia-reperfusion in rat heart model

作　　者：王旭东[1] 王占明[2] 贾东林[3] 于彭[4] 

机构地区：[1]航天中心医院心胸外科,北京100049 [2]中国医科大学第二临床医院心外科 [3]北京大学第三医院麻醉科 [4]复旦大学附属中山医院血管外科

出　　处：《中华医学杂志》2007年第25期1789-1791,共3页National Medical Journal of China

摘　　要：目的研究17β-雌二醇(E_2)对缺血再灌注心肌诱生型一氧化氮合酶(iNOS)及内皮型一氧化氮合酶(eNOS)活性的影响,并探讨其心肌保护作用机制。方法采用 Langendorff 离体鼠心脏灌注模型,将40只卵巢切除(OVX)大鼠随机均分为心肌缺血前对照组(C 组):离体鼠心脏预灌注15 min;缺血再灌注组(I-R 组):灌注改良St.ThomasⅡ停搏液,完成心肌缺血再灌注全过程;溶剂对照组(D 组):停搏液中含0.1%的二甲基亚砜(DMSO),余同 I-R 组;E_2组(E 组):停搏液中含0.1%DMSO 及5 μmol/L 的 E_2,余同 I-R 组。检测缺血再灌注前后心肌 iNOS 和 eNOS 活性变化,测定冠状动脉流出液中肌酸磷酸激酶(CPK)、乳酸脱氢酶(LDH)、一氧化氮(NO)的含量以及心脏功能的变化,观察 E_2对心肌缺血再灌注损伤(MIRI)的影响。结果心肌缺血再灌注后 eNOS 活性下降(P<0.01),iNOS 活性升高[C 组(8.9±3.7)nmol·min^(-1)·g^(-1),I-R 组(15.8±2.4)nmol·min^(-1)·g^(-1),D组(17.6±3.2)nmol·min^(-1)·g^(-1),P<0.01],E 组 iNOS 活性升高更明显[(25.85±5.21)nmol·min^(-1)·g^(-1),P<0.01],I-R 组及 D 组 NO 生成减少(均 P<0.05),E 组 NO 增加[C 组(31±5)μmol/L,E 组(33±6)μmol/L,P<0.01],E 组 CPK 和 LDH 产生减少(均 P<0.05),E 组心脏功能恢复良好(P<0.05)。结论 E_2通过提高诱生型一氧化氮合酶活性,促进一氧化氮的产生,减轻心肌缺血再灌注损伤,促进心脏功能恢复。Objective To study the effect of 17βestradiol （E2） on myocardial inducible nitric oxide synthase （iNOS）and endothelial nitric oxide synthase （eNOS） activitivies of ischemia-reperfusion myocardium in rat model. Methods 40 Langendorff perfused hearts isolated from bilateral ovariectomy （OVX） rat were randomly divided into four groups： control group （Group C ）, in which hearts were reperfused ex vivo for 15 minutes before ischemia in rat; ischemia-reperfusion control （ Group I-R）, in which modified St. Thomas 11 cardiopiegic solution was perfused to perform the ischemia-reperfusion; dissolvent control group （Group D ）, in which 0. 1% dimethyl sulfoxide （DMSO） was dissolved in cardiopiegic solution ; E2 group （ Group E）, in which 0. 1% DMSO and 5 μmol of E2 were dissolved in cardiopiegic solution. Myocardial iNOS and eNOS activities were detected before and after reperfusion. Creatin phosphokinase（CPK）, lactec dehydrogenase（LDH） and nitric oxide （NO） of coronary flow were measured, and heart function was evaluated to observe the effect of E2 on myocardial ischemia-reperfusion injury （MIRI）. Results Myocardial eNOS activity declined （P 〈 0. 01 ）and iNOS activity increased after ischemia-reperfusion （8. 87 ± 3.74 nmol/min/g in Group C, 15.83± 2.42 nmol/min/g in Group I-R, 17. 60 ±5.21 nmol/min/g in Group E; P 〈0. 01 ） , moreover, iNOS activity was much higher in Group E （25.85 ±5.21 nmol/min/g , P 〈0. 01 ）. NO production was lower in Group I-R and Group D （P 〈0. 05）, and higher in Group E （30.96 ±4. 91 μmol/L in Group C, 33. 16 ±5.57 μmol/L in Group E; P 〈0. 01 ）. CPK and LDH were lower in Group E （ P 〈 0. 05 ）. Recovery of heart function was better in Group E （ P 〈 0. 05 ）. Conclusions E2 can relieve the injury of MIRI and promote heart function recovery by increasing iNOS activity and NO production.

关 键 词：雌二醇 一氧化氮合酶 内皮型一氧化氮合酶 心肌再灌注损伤 

分 类 号：R363[医药卫生—病理学]