Intermedin在大鼠急性心肌缺血再灌注损伤中的作用  

Effects and mechanism of intermedin on ischemia/reperfusion injury in rats heart

作　　者：杜秋香[1] 牛艳麟[2] 岳维[3] 刘佳佳[1] 王英元[1] 

机构地区：[1]山西医科大学法医学院法医病理学教研室,山西太原030001 [2]太原市公安局晋源分局,山西太原030025 [3]山西医科大学第二附属医院麻醉实验室,山西太原030001

出　　处：《中国法医学杂志》2011年第3期197-200,262,共5页Chinese Journal of Forensic Medicine

摘　　要：目的探讨Intermedin(IMD)对大鼠急性心肌缺血再灌注损伤的作用。方法 72只健康雄性SD大鼠随机分为3组:对照组;缺血再灌注组(缺血1h再灌30min);IMD预处理组(缺血再灌注前30min静脉注射10-7mol/L IMD)。检测血清中LDH、心肌中MDA和SOD活性;半定量实时荧光PCR法检测心肌降钙素受体样受体(calcitonin receptor likereceptor,CRLR)、受体活性修饰蛋白(receptor activity modifying protein,RAMP)1/2/3的mRNA表达水平;酶联免疫吸附法(ELISA)测定心肌cAMP含量,SABC法检测Bcl-2/Bax蛋白表达及比值。结果与对照组比较,缺血再灌注组大鼠LDH、MDA分别升高87%和189%,SOD活性下降84%,IMD预处理组LDH、MDA均降低41%,SOD活性升高38%(均P<0.01);实验组心肌CRLR、RAMP1/2/3的mRNA水平均明显上调(P<0.05或P<0.01),与对照组心肌cAMP相比,缺血再灌注组和IMD预处理组分别升高1.36、2.90倍(P<0.05)。Bcl-2/Bax表达比值,缺血再灌注组较对照组降低,IMD预处理组亦低于对照组但高于缺血再灌注组2.225倍。结论 IMD对大鼠急性缺血再灌注损伤的心肌有一定保护作用,减少缺血再灌所致的氧化应激,抑制心肌细胞凋亡可能是其作用机制之一。Objective To study the effects of intermedin on acute heart ischemia-reperfusion （I/R）injury. Methods Seventy two healthy male Sprague-Dawley rats weighing 250 - 300g were divided into 3 groups ： control group; I/R group in which therats heart were subjected to ischemic for lh followed by 30 min reperfusion ;the intermedin-treated group which the rats was treated by venous injection （iv） of 10^-7 mol/Lintermedin 30 min prior to the I/R treatment. Myocardial injury was determined by measurement of lactate dehydrogenase （LDH） leakage, MDA creation and superoxide dismutase （SOD） activity. The mRNA changes of calcitonin receptor like receptor（CRLR） and receptor activity modifying protein （RAMP）1/2/3 in left ventrieular were measured by reahime PCR analysis. Myocardial cAMP content was determined by enzyme linked immunosorbent assay（ELISA）. Expression of apoptosis related factors Bcl-2 and Bax were detected by Immunohistochemistry. Results LDH leakage and MDA of I/R group increased by 87% and 189% compared with the control group,while the SOD activity decrease by 84% ,administration with IMD attenuated the LDH leakage and MDA both by 41% ,and SOD activity increase by 38% （P 〈0.01 ）compared with the I/R group. （RAMP）1/2/3 in ventricular mRNA expression elevated in both two experiment groups （P 〈 0. 05 or P 〈 0. 01 ）. The concentration of cyclic adenosine monophosphate（cAMP） was increased by 1.36times and 2. 90 times in the I/R group and IMD-treated group, respectively （both P 〈0.05）. Immunohistochemistry staining showed the significant decrease of ratio of BCL-2/BAX in I/R group ,while an increasement of 2.225 times of the I/R group was observed in the IMD-treated groups （bothP 〈 0.01 ）. Conclusion Our results suggest that the protective effect of IMD against myocardial I/R injury is due to the inhibition of myocardial apoptosis.

关 键 词：法医病理学 INTERMEDIN 心肌缺血再灌注损伤 凋亡 

分 类 号：D919[医药卫生—法医学]