脂联素对大鼠心肌缺血再灌注损伤的保护作用

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.

Protective effects of adiponectin on myocardial ischemia-reperfusion injury in rats

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.