中华心血管病杂志
中華心血管病雜誌
중화심혈관병잡지
Chinese Journal of Cardiology
2012年
12期
991-996
,共6页
罗秀菊%吉绍葵%刘斌%张洪峰%杨中保%马琦琳
囉秀菊%吉紹葵%劉斌%張洪峰%楊中保%馬琦琳
라수국%길소규%류빈%장홍봉%양중보%마기림
心肌再灌注损伤%NADPH氧化酶%过氧化物酶类
心肌再灌註損傷%NADPH氧化酶%過氧化物酶類
심기재관주손상%NADPH양화매%과양화물매류
Myocardial reperfusion injury%NADPH oxidase%Peroxidases
目的 研究还原型辅酶Ⅱ(NADPH)氧化酶/血管过氧化酶(NOX/VPO)途径在心肌缺血再灌注(I/R)氧化损伤中的作用和机制.方法 雄性SD大鼠分为正常对照组,假手术组,缺血再灌注组(I/R组,大鼠心肌缺血1h,再灌注3h),夹竹桃麻素(apocynin)处理组(I/R+ apocynin组,再灌注开始前30 min腹腔注射NOX特异性抑制剂apocynin)和溶媒对照组(I/R+ vehicle组,再灌注开始前30 min腹腔注射等体积apocynin溶媒).每组动物数为7～8只.再灌注结束后测定心肌梗死面积、血清肌酸激酶(CK)活性、心肌组织细胞凋亡率和心肌组织细胞凋亡蛋白酶(caspase-3)含量及活性、NOX活性、NOX2和VPO1 mRNA和蛋白表达水平.结果 I/R组VPO1、NOX2mRNA和蛋白表达水平、NOX2酶活性水平、CK水平、心肌梗死面积、心肌细胞凋亡率均显著高于假手术组[两组上述指标分别为2.01 ±0.20比1.01 ±0.10,0.02 ±0.39比1.12 ±0.08,1.15±0.14比0.52 ±0.08,0.82±0.08比0.53 ±0.07,(14.1 ±1.2)比(9.1±1.2) μmol· L-1· min-1· g-1,(2838.5 ±315.2)比(715.1±121.2) U/L,(52.1±2.1)％比(0.9±0.1)％和(23.5±3.5)％比(1.8±0.5)％,P均＜0.01].I/R+ apocynin组VPO1、NOX2mRNA和蛋白表达水平、NOX2酶活性水平、CK水平、心肌梗死面积、心肌细胞凋亡率[分别为1.51 ±0.20,0.76 ±0.06,(12.1 ± 1.0)μmol·L-1·min-1·g-1,(1795.2 ±206.3)U/L,(21.5±2.2)％和(8.9±2.3)％]均显著低于I/R组(P均＜0.01).I/R+vehicle组上述指标与I/R组比较差异均无统计学意义.结论 NOX2/VPO1途径在I/R氧化损伤中起重要作用,VPO1与NOX2可能以H2O2为中介,共同促进了I/R造成的氧化损伤.
目的 研究還原型輔酶Ⅱ(NADPH)氧化酶/血管過氧化酶(NOX/VPO)途徑在心肌缺血再灌註(I/R)氧化損傷中的作用和機製.方法 雄性SD大鼠分為正常對照組,假手術組,缺血再灌註組(I/R組,大鼠心肌缺血1h,再灌註3h),夾竹桃痳素(apocynin)處理組(I/R+ apocynin組,再灌註開始前30 min腹腔註射NOX特異性抑製劑apocynin)和溶媒對照組(I/R+ vehicle組,再灌註開始前30 min腹腔註射等體積apocynin溶媒).每組動物數為7～8隻.再灌註結束後測定心肌梗死麵積、血清肌痠激酶(CK)活性、心肌組織細胞凋亡率和心肌組織細胞凋亡蛋白酶(caspase-3)含量及活性、NOX活性、NOX2和VPO1 mRNA和蛋白錶達水平.結果 I/R組VPO1、NOX2mRNA和蛋白錶達水平、NOX2酶活性水平、CK水平、心肌梗死麵積、心肌細胞凋亡率均顯著高于假手術組[兩組上述指標分彆為2.01 ±0.20比1.01 ±0.10,0.02 ±0.39比1.12 ±0.08,1.15±0.14比0.52 ±0.08,0.82±0.08比0.53 ±0.07,(14.1 ±1.2)比(9.1±1.2) μmol· L-1· min-1· g-1,(2838.5 ±315.2)比(715.1±121.2) U/L,(52.1±2.1)％比(0.9±0.1)％和(23.5±3.5)％比(1.8±0.5)％,P均＜0.01].I/R+ apocynin組VPO1、NOX2mRNA和蛋白錶達水平、NOX2酶活性水平、CK水平、心肌梗死麵積、心肌細胞凋亡率[分彆為1.51 ±0.20,0.76 ±0.06,(12.1 ± 1.0)μmol·L-1·min-1·g-1,(1795.2 ±206.3)U/L,(21.5±2.2)％和(8.9±2.3)％]均顯著低于I/R組(P均＜0.01).I/R+vehicle組上述指標與I/R組比較差異均無統計學意義.結論 NOX2/VPO1途徑在I/R氧化損傷中起重要作用,VPO1與NOX2可能以H2O2為中介,共同促進瞭I/R造成的氧化損傷.
목적 연구환원형보매Ⅱ(NADPH)양화매/혈관과양화매(NOX/VPO)도경재심기결혈재관주(I/R)양화손상중적작용화궤제.방법 웅성SD대서분위정상대조조,가수술조,결혈재관주조(I/R조,대서심기결혈1h,재관주3h),협죽도마소(apocynin)처리조(I/R+ apocynin조,재관주개시전30 min복강주사NOX특이성억제제apocynin)화용매대조조(I/R+ vehicle조,재관주개시전30 min복강주사등체적apocynin용매).매조동물수위7～8지.재관주결속후측정심기경사면적、혈청기산격매(CK)활성、심기조직세포조망솔화심기조직세포조망단백매(caspase-3)함량급활성、NOX활성、NOX2화VPO1 mRNA화단백표체수평.결과 I/R조VPO1、NOX2mRNA화단백표체수평、NOX2매활성수평、CK수평、심기경사면적、심기세포조망솔균현저고우가수술조[량조상술지표분별위2.01 ±0.20비1.01 ±0.10,0.02 ±0.39비1.12 ±0.08,1.15±0.14비0.52 ±0.08,0.82±0.08비0.53 ±0.07,(14.1 ±1.2)비(9.1±1.2) μmol· L-1· min-1· g-1,(2838.5 ±315.2)비(715.1±121.2) U/L,(52.1±2.1)％비(0.9±0.1)％화(23.5±3.5)％비(1.8±0.5)％,P균＜0.01].I/R+ apocynin조VPO1、NOX2mRNA화단백표체수평、NOX2매활성수평、CK수평、심기경사면적、심기세포조망솔[분별위1.51 ±0.20,0.76 ±0.06,(12.1 ± 1.0)μmol·L-1·min-1·g-1,(1795.2 ±206.3)U/L,(21.5±2.2)％화(8.9±2.3)％]균현저저우I/R조(P균＜0.01).I/R+vehicle조상술지표여I/R조비교차이균무통계학의의.결론 NOX2/VPO1도경재I/R양화손상중기중요작용,VPO1여NOX2가능이H2O2위중개,공동촉진료I/R조성적양화손상.
Objective To explore the role of NADPH oxidase inhibitor apocynin on ischemia/reperfusion (I/R)-induced myocardial injury.Methods Male SD rat hearts were divided into the normal control group; sham group; I/R group (1 h ischemia followed by 3 h reperfusion) ; I/R + apocynin group (50 mg/kg,administrated at 30 min before reperfusion) and I/R + vehicle group (same volume vehicle administrated at 30 min before reperfusion).At the end of reperfusion,myocardial infarct size,apoptosis,plasma CK activity,myocardial NOX activity,myocardial caspase-3 expression and activity,myocardial mRNA and protein expressions of vascular peroxidase 1 (VPO1) and NOX2 were measured.Results Infarct size,ratio of cardiomyocyte apoptosis,mRNA and protein expression of VOP1 and NOX2,serum CK,myocardial NOX and caspase-3 activities in the I/R group were all significantly increased compared to those in the sham group (P ＜0.01).Above parameters were similar between I/R + vehicle group and I/R group (all P ＞ 0.05).Infarct size,ratio of cardiomyocyte apoptosis,myocardial mRNA and protein expression of VOP1 and NOX2,serum CK,myocardial NOX and caspase-3 activities were significantly lower in I/R + apocynin group compared to those in I/R group (all P ＜ 0.01).Conclusions NOX/VPO pathway plays an important role in mediating I/R-induced myocardial oxidative injury.NOX inhibition could reduce I/R-induced myocardial oxidative injury by attenuating myocardial apoptosis in this model.
