肾上腺髓质素对骨骼肌缺血再灌注损伤的影响

Effect of adrenomedulin on skeletal muscle ischemia/reperfusion injury in rats

背景:作为一种新发现的内分泌激素,研究表明肾上腺髓质素能在多种重要器官的缺血再灌注损伤中起到保护作用,是否能对骨骼肌缺血再灌注有保护作用有待研究。目的:观察肾上腺髓质素对大鼠骨骼肌缺血再灌注损伤的影响。设计、时间及地点:随机对照动物实验,于2007-03/07在湖南师范大学医学院机能实验室、分子生物学实验室完成。材料:健康雄性SD大鼠30只,随机分为对照组,缺血再灌注组,0.1,0.5,1.0nmol/kg肾上腺髓质素处理组,每组6只。方法:无创动脉夹夹闭右侧股动脉4h,再灌注3h,建立后肢骨骼肌缺血再灌注损伤模型。对照组仅暴露出股动静脉,不做血管夹闭和环扎。肢体再灌注前肾上腺髓质素处理组分别自尾静脉注射0.1,0.5,1.0nmol/kg肾上腺髓质素生理盐水溶液,对照组及缺血再灌注组注射等量生理盐水。主要观察指标:测定各组血清肌酸激酶、乳酸脱氢酶活性;取术侧腓肠肌,测定组织中超氧化物歧化酶、髓过氧化物酶的活性、丙二醛水平并观察骨骼肌组织形态学变化。结果:30只大鼠均进入结果分析。①与对照组比较,缺血再灌注组肌酸激酶、乳酸脱氢酶、丙二醛、髓过氧化物酶值增高(P<0.01),超氧化物歧化酶值降低(P<0.01);腓肠肌超微结构损伤明显加重。②与缺血再灌注组比较,肾上腺髓质素处理组肌酸激酶、乳酸脱氢酶、丙二醛、髓过氧化物酶值减低,超氧化物歧化酶值增高。0.1nmol/kg肾上腺髓质素处理组与缺血再灌注组比较,肌酸激酶、丙二醛的变化无统计学意义(P>0.05),其他均有统计学意义(P<0.05～0.01)。③0.5nmol/kg肾上腺髓质素处理组肌酸激酶、髓过氧化物酶、丙二醛值低于0.1nmol/kg肾上腺髓质素处理组(P<0.05),1.0nmol/kg肾上腺髓质素处理组肌酸激酶值低于0.1nmol/kg肾上腺髓质素处理组(P<0.05)。0.1nmol/kg肾上腺髓质素处理组腓肠肌超微结构损伤相对加重。结论:肾上腺髓质素可减轻缺血再灌注对骨骼肌造成的损伤,对缺血再灌注骨骼肌具有保护作用。

BACKGROUND： Previous studies have showed that adrenomedullin （ADM） plays a protective role in tissue ischemia/reperfusion （IR）. However, whether ADM can protect skeletal muscle ischemia/reperfusion injury needs to further explore. OBJECTIVE： To investigate the effect of ADM on skeletal muscle IR injury. DESIGN, TIME AND SETTING： The experiment was carried out in the Laboratory of Functional Sciences and the Laboratory of Molecular Biology at Medical College of Hunan Nomal Univercity from March 2007 to July 2007. MATERIALS： A total of 30 healthy, male, Sprague Dawley rats were randomly divided into the control, IR, ADM treatment groups of dose of 0.1, 0.5, 1.0 nmol/kg, with 6 animals in each group. METHODS： The rats in each group were subjected to 4 hours occlusion of right femoral artery followed by 3 hours reperfusion, except the animal in the control group. Animal in the ADM treatment were accepted intravenous injection 0.1,0.5, 1.0nmol/kg ADM respectively. The equivalent normal saline was injected into rats in control group and IR group. MAIN OUTCOME MEASURES： The activity of serum creatine kinase （CK）, lactic dehydrogenase （LDH）, superoxide dismutase （SOD）, myeloperoxidase （MPO） and malondialdehyde （MDA） were detected. The histomorphological changes of skeletal muscles were observed. RESULTS： A total of 30 animals were included in the final analysis. （1）The contents of LDH, CK, MDA, MPO in IR group were dramatically higher than （P 〈 0.01）, and the content of SOD was decreased than of the control group （P 〈 0.01）, the ultrastructure of skeletal muscle was significantly serious. （2）Compared with the IR group, the contents of LDH, CK, MDA, and MPO in the ADM groups were obvious decreased than the IR group, but the SOD was higher. There were significantly differences between the 0.1 nmol/kg treatment group and the IR group except the content of CK and MDA （P〈 0.05-0,01）. The ultrastructure of skeletal muscle in the ADM group was significantly improved compared with IR group. （3）The contents of CK, MPO, MDA in the 0.5 nmol/kg ADM treatment group were lower in than that of 0.1 nmol/kg ADM treatment group （P 〈 0.05）, while the content of CK in the 1.0 nmol/kg ADM treatment group were dramatically lower than the 0.1 nmol/kg ADM treatment group, the injury of skeletal muscle ultrastructure in the 0.5 nmol/kg ADM treatment group was relative serious. CONCLUSION： ADM has a protective effect on ischemia/reperfusion injury in skeletal muscle.