中国病理生理杂志
中國病理生理雜誌
중국병리생리잡지
CHINESE JOURNAL OF PATHOPHYSIOLOGY
2014年
10期
1760-1764
,共5页
促红细胞生成素%压力超负荷%NADPH氧化酶
促紅細胞生成素%壓力超負荷%NADPH氧化酶
촉홍세포생성소%압력초부하%NADPH양화매
Erythropoietin%Pressure overload%NADPH oxidase
目的:探讨促红细胞生成素( EPO)对压力超负荷大鼠心肌NADPH氧化酶的影响。方法:36只SD雄性大鼠,腹主动脉结扎复制压力超负荷心肌肥大模型。动物随机分成3组:模型组;假手术组:除不缩窄腹主动脉外,其余操作同腹主动脉缩窄组;重组人促红细胞生成素( rhEPO)治疗组( EPO治疗组):术后给予rhEPO,腹腔注射4000 U/kg,每周2次。8周后采用心动超声和血流动力学评价心功能;Masson染色观察心肌纤维化程度;实时定量PCR法和Western blotting法检测NADPH氧化酶2( Nox2)和Nox4 mRNA及蛋白表达的变化;Western blotting法观察心肌炎症因子CD45、F4/80和转化生长因子β( TGF-β)的表达变化。结果:与模型组比较,EPO治疗组左室射血分数(LVEF)、左室短轴缩短率(LVFS)、左室收缩末压(LVESP)及左室内压最大上升和下降速率(±dp/dtmax)明显升高( P<0.01),左室收缩末内径(LVESD)、舒张末内径(LVEDD)及左室舒张末压(LVEDP)下降(P<0.01);同时,EPO可降低压力超负荷所致的心肌纤维化程度(P<0.01),降低心室肌中 Nox2、Nox4 mRNA和蛋白的表达(P<0.05或P<0.01)及心肌炎症因子CD45、F4/80、TGF-β蛋白的表达。结论: EPO可抑制压力超负荷所致大鼠的心肌纤维化,改善心功能,其机制可能与降低NADPH氧化酶活性,抑制心肌氧化应激水平,减少心肌炎症反应有关。
目的:探討促紅細胞生成素( EPO)對壓力超負荷大鼠心肌NADPH氧化酶的影響。方法:36隻SD雄性大鼠,腹主動脈結扎複製壓力超負荷心肌肥大模型。動物隨機分成3組:模型組;假手術組:除不縮窄腹主動脈外,其餘操作同腹主動脈縮窄組;重組人促紅細胞生成素( rhEPO)治療組( EPO治療組):術後給予rhEPO,腹腔註射4000 U/kg,每週2次。8週後採用心動超聲和血流動力學評價心功能;Masson染色觀察心肌纖維化程度;實時定量PCR法和Western blotting法檢測NADPH氧化酶2( Nox2)和Nox4 mRNA及蛋白錶達的變化;Western blotting法觀察心肌炎癥因子CD45、F4/80和轉化生長因子β( TGF-β)的錶達變化。結果:與模型組比較,EPO治療組左室射血分數(LVEF)、左室短軸縮短率(LVFS)、左室收縮末壓(LVESP)及左室內壓最大上升和下降速率(±dp/dtmax)明顯升高( P<0.01),左室收縮末內徑(LVESD)、舒張末內徑(LVEDD)及左室舒張末壓(LVEDP)下降(P<0.01);同時,EPO可降低壓力超負荷所緻的心肌纖維化程度(P<0.01),降低心室肌中 Nox2、Nox4 mRNA和蛋白的錶達(P<0.05或P<0.01)及心肌炎癥因子CD45、F4/80、TGF-β蛋白的錶達。結論: EPO可抑製壓力超負荷所緻大鼠的心肌纖維化,改善心功能,其機製可能與降低NADPH氧化酶活性,抑製心肌氧化應激水平,減少心肌炎癥反應有關。
목적:탐토촉홍세포생성소( EPO)대압력초부하대서심기NADPH양화매적영향。방법:36지SD웅성대서,복주동맥결찰복제압력초부하심기비대모형。동물수궤분성3조:모형조;가수술조:제불축착복주동맥외,기여조작동복주동맥축착조;중조인촉홍세포생성소( rhEPO)치료조( EPO치료조):술후급여rhEPO,복강주사4000 U/kg,매주2차。8주후채용심동초성화혈류동역학평개심공능;Masson염색관찰심기섬유화정도;실시정량PCR법화Western blotting법검측NADPH양화매2( Nox2)화Nox4 mRNA급단백표체적변화;Western blotting법관찰심기염증인자CD45、F4/80화전화생장인자β( TGF-β)적표체변화。결과:여모형조비교,EPO치료조좌실사혈분수(LVEF)、좌실단축축단솔(LVFS)、좌실수축말압(LVESP)급좌실내압최대상승화하강속솔(±dp/dtmax)명현승고( P<0.01),좌실수축말내경(LVESD)、서장말내경(LVEDD)급좌실서장말압(LVEDP)하강(P<0.01);동시,EPO가강저압력초부하소치적심기섬유화정도(P<0.01),강저심실기중 Nox2、Nox4 mRNA화단백적표체(P<0.05혹P<0.01)급심기염증인자CD45、F4/80、TGF-β단백적표체。결론: EPO가억제압력초부하소치대서적심기섬유화,개선심공능,기궤제가능여강저NADPH양화매활성,억제심기양화응격수평,감소심기염증반응유관。
AIM:To explore the effect of erythropoietin ( EPO) on the expression of myocardial NADPH oxi-dase (Nox) in the pressure overload rats.METHODS:Male SD rats (n=36) were used to establish a pressure overload myocardial hypertrophy model by abdominal aorta ligation.The animals were divided into model group, control group ( sham, without narrowing abdominal aorta, the rest of the operation was the same as the model) and recombinant human erythropoietin ( rhEPO) treatment group ( intraperitoneal injection of rhEPO postoperatively, 4 000 U/kg, twice a week) . After 8 weeks, the cardiac ultrasound imaging and hemodynamic evaluation were conducted to determine the cardiac func-tions.Masson staining was used to observe the degree of myocardial fibrosis.The expression of Nox2 and Nox4 at mRNA and protein levels was detected by real-time quantitative PCR and Western blotting.The protein levels of myocardial inflam-matory factors CD45, F4/80 and TGF-βwere determined by Western blotting.RESULTS:Compared with model group, the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-systolic pressure (LVESP) and left ventricular pressure maximum rising and falling rates ( ±dp/dtmax) increased significantly in EPO treatment group (P<0.01).At the same time, left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter ( LVEDD) and left ventricular end-diastolic pressure ( LVEDP) were decreased in EPO treatment group (P<0.01).EPO reduced the degree of myocardial fibrosis caused by pressure overload (P<0.01) and decreased the ex-pression of Nox2 and Nox4 at mRNA and protein levels in the myocardium (P<0.05 or P<0.01), and reduced the pro-tein expression of myocardial inflammatory factors CD45, F4/80 and TGF-β.CONCLUSION: EPO inhibits rat myocar-dial fibrosis induced by pressure overload, improves heart functions by decreasing NADPH oxidase activity and inhibiting myocardial oxidative stress levels and myocardial inflammatory reaction.