中华心血管病杂志
中華心血管病雜誌
중화심혈관병잡지
Chinese Journal of Cardiology
2010年
3期
252-258
,共7页
汪俊%邵名亮%曹蘅%柯永胜
汪俊%邵名亮%曹蘅%柯永勝
왕준%소명량%조형%가영성
心肌再灌注损伤%脂联素%细胞凋亡
心肌再灌註損傷%脂聯素%細胞凋亡
심기재관주손상%지련소%세포조망
Myocardial reperfusion injury%Adiponectin%Apoptosis
目的 观察脂联素对大鼠心肌缺血再灌注损伤的保护作用并探讨其机制.方法 32只8周龄雄性大鼠随机分为假手术组、缺血再灌注组、地尔硫革组和脂联素组,每组8只.(1)假手术组:只穿线,旷置90 min.(2)缺血再灌注组:先阻断血流30 min,再灌注60 min.(3)地尔硫(革)组和脂联素组:先阻断血流30 min,于再灌注开始时,从鼠尾静脉分别注射地尔硫(革)(3.5 μg·g~(-1)min~(-1))或脂联素(60 ng·g~(-1)·min~(-1)),注射2 min,再灌注60 min.各模型组于再灌注60 min后处死大鼠.测定心肌组织一氧化氮(NO),心肌组织半胱氨酸蛋白酶3(Caspase 3)活性,心肌组织腺苷酸活化蛋白激酶(AMPK)活性,过氧化物酶体增殖物激活受体γ(PPARγ)的含量,同时用透射电镜观察大鼠心肌线粒体结构.结果 (1)缺血再灌注组心肌组织中Caspase 3活性显著高于假手术组[(168.50±30.08)μmol/L比(53.25±11.41)μmol/L,P<0.01],AMPK活性、PPARγ含量均显著低于假手术组[(0.74±0.59)IU/ml比(25.63±4.61)IU/ml,P<0.01;0.1894比0.7949,P<0.01],心肌组织中NO含量显著低于假手术组[(6.359±1.355)μmol/L比(10.396±1.901)μmol.L,P<0.01].(2)脂联素组心肌组织中Caspase 3活性显著低于缺血再灌注组[(88.75±6.92)μmol/L比(168.50±30.08)μmol/L,P<0.01],AMPK活性、PPARγ含量均显著高于缺血再灌注组[(27.22 ±4.76)IU/ml比(0.74±0.59)IU/ml,P<0.01;0.8613比0.1894,P<0.01],心肌组织中NO含量显著高于缺血再灌注组[(15.755±1.045)μmol/L比(6.359±1.355)μmol/L,P<0.01].脂联素可保护急性心肌缺血再灌注过程中大鼠心肌细胞线粒体结构的完整性,上述作用优于地尔硫(革).结论 脂联素对缺血再灌注造成的心肌损伤有一定的保护作用,机制可能与其增加心肌细胞AMPK、PPARγ表达,以及抗心肌细胞凋亡作用有关.
目的 觀察脂聯素對大鼠心肌缺血再灌註損傷的保護作用併探討其機製.方法 32隻8週齡雄性大鼠隨機分為假手術組、缺血再灌註組、地爾硫革組和脂聯素組,每組8隻.(1)假手術組:隻穿線,曠置90 min.(2)缺血再灌註組:先阻斷血流30 min,再灌註60 min.(3)地爾硫(革)組和脂聯素組:先阻斷血流30 min,于再灌註開始時,從鼠尾靜脈分彆註射地爾硫(革)(3.5 μg·g~(-1)min~(-1))或脂聯素(60 ng·g~(-1)·min~(-1)),註射2 min,再灌註60 min.各模型組于再灌註60 min後處死大鼠.測定心肌組織一氧化氮(NO),心肌組織半胱氨痠蛋白酶3(Caspase 3)活性,心肌組織腺苷痠活化蛋白激酶(AMPK)活性,過氧化物酶體增殖物激活受體γ(PPARγ)的含量,同時用透射電鏡觀察大鼠心肌線粒體結構.結果 (1)缺血再灌註組心肌組織中Caspase 3活性顯著高于假手術組[(168.50±30.08)μmol/L比(53.25±11.41)μmol/L,P<0.01],AMPK活性、PPARγ含量均顯著低于假手術組[(0.74±0.59)IU/ml比(25.63±4.61)IU/ml,P<0.01;0.1894比0.7949,P<0.01],心肌組織中NO含量顯著低于假手術組[(6.359±1.355)μmol/L比(10.396±1.901)μmol.L,P<0.01].(2)脂聯素組心肌組織中Caspase 3活性顯著低于缺血再灌註組[(88.75±6.92)μmol/L比(168.50±30.08)μmol/L,P<0.01],AMPK活性、PPARγ含量均顯著高于缺血再灌註組[(27.22 ±4.76)IU/ml比(0.74±0.59)IU/ml,P<0.01;0.8613比0.1894,P<0.01],心肌組織中NO含量顯著高于缺血再灌註組[(15.755±1.045)μmol/L比(6.359±1.355)μmol/L,P<0.01].脂聯素可保護急性心肌缺血再灌註過程中大鼠心肌細胞線粒體結構的完整性,上述作用優于地爾硫(革).結論 脂聯素對缺血再灌註造成的心肌損傷有一定的保護作用,機製可能與其增加心肌細胞AMPK、PPARγ錶達,以及抗心肌細胞凋亡作用有關.
목적 관찰지련소대대서심기결혈재관주손상적보호작용병탐토기궤제.방법 32지8주령웅성대서수궤분위가수술조、결혈재관주조、지이류혁조화지련소조,매조8지.(1)가수술조:지천선,광치90 min.(2)결혈재관주조:선조단혈류30 min,재관주60 min.(3)지이류(혁)조화지련소조:선조단혈류30 min,우재관주개시시,종서미정맥분별주사지이류(혁)(3.5 μg·g~(-1)min~(-1))혹지련소(60 ng·g~(-1)·min~(-1)),주사2 min,재관주60 min.각모형조우재관주60 min후처사대서.측정심기조직일양화담(NO),심기조직반광안산단백매3(Caspase 3)활성,심기조직선감산활화단백격매(AMPK)활성,과양화물매체증식물격활수체γ(PPARγ)적함량,동시용투사전경관찰대서심기선립체결구.결과 (1)결혈재관주조심기조직중Caspase 3활성현저고우가수술조[(168.50±30.08)μmol/L비(53.25±11.41)μmol/L,P<0.01],AMPK활성、PPARγ함량균현저저우가수술조[(0.74±0.59)IU/ml비(25.63±4.61)IU/ml,P<0.01;0.1894비0.7949,P<0.01],심기조직중NO함량현저저우가수술조[(6.359±1.355)μmol/L비(10.396±1.901)μmol.L,P<0.01].(2)지련소조심기조직중Caspase 3활성현저저우결혈재관주조[(88.75±6.92)μmol/L비(168.50±30.08)μmol/L,P<0.01],AMPK활성、PPARγ함량균현저고우결혈재관주조[(27.22 ±4.76)IU/ml비(0.74±0.59)IU/ml,P<0.01;0.8613비0.1894,P<0.01],심기조직중NO함량현저고우결혈재관주조[(15.755±1.045)μmol/L비(6.359±1.355)μmol/L,P<0.01].지련소가보호급성심기결혈재관주과정중대서심기세포선립체결구적완정성,상술작용우우지이류(혁).결론 지련소대결혈재관주조성적심기손상유일정적보호작용,궤제가능여기증가심기세포AMPK、PPARγ표체,이급항심기세포조망작용유관.
Objective To investigate the protective effects of ediponectin on myocardial ischemiareperfusion injury and the potential mechanisms in rats. Methods Thirty-two male rats aged 8 weeks were randomly assigned to sham operation (sham), myocardial ischemia-reperfusion (MIR), diltiazem treatment (diltiazem) or adiponectin administration (APN) groups ( n=8 each). MIR rats underwent left anterior descending artery(LAD) occlusion for 30 min followed by 60 min reperfusion. Diltiazem (7 μg/g) and APN ( 120 ng/g) were given by caudal intravenous injection at the end of 30 min ischemia and the beginning of reperfusion for rats in dihiazem or APN groups. Animals were sacrificed after 60 mim reperfusion for determining the myocardial nitric oxide (NO), Caspase 3, activity of AMP-activated protein kinase(AMPK) and concentration of peroxisome proliferators-activaated receptor γ (PPARγ). Apoptotic cells were stained by Caspase 3 Activity Assay Kit and mitochondria in myocardial cells were observed by transmission electron microscope (TEM). Results The myocardial Caspase 3 level was significantly increased [ (168.50±30. 08) μmol/L vs. (53. 25±11.41 )μmol/L,P <0. 01 ], AMPK activity, PPARγ and NO concentrations were significantly reduced in MIR group compared with those in sham group (all P <0. 05) [ (0. 74±0. 59)IU/ml vs. (25.63±4. 61) IU/ml, P < 0. 01 ; 0. 1894 vs. 0. 7949, P < 0. 01 ; (6. 359±1. 355 )μmol/L vs.( 10. 396±1. 901 ) μmol/L,P <0. 01 ], these effects could be significantly reversed by APN. In comparison with MIR group, the levds of Caspase 3 in cardiac muscles were significantly lowered in Adiponectin group [ (88. 75±6. 92 ) μmol/L vs. ( 168.50±30. 08 ) μmol/L, P < 0. 01 ], whereas the level of AMPK and PPARγ, NO concentration in the cardiac muscle was remarkably increased [ ( 27.22±4. 76 ) IU/ml vs.(0. 74±0. 59 ) IU/ml, P < 0. 01 ; 0. 8613 vs. 0. 1894, P < 0. 01 ; ( 15. 755±1. 045 ) μmol/L vs. ( 6. 359±1. 355) μmol/L, P < 0. 01 ]. APN also preserved the function and structure of mitochondria in rats post ischemia/reperfusion injury. The protective pharmacologic actions of APN were superior to that of diltiazerm. Conclusion Adiponectin could protect myocardial tissues from myocardial ischemia-reperfusion injury in rats, possibly by upregulating myocardial AMPK and PPARγ expressions and preventing myocardial cells from apoptosis.
