Intermedin在大鼠急性心肌缺血再灌注损伤中的作用

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／LIMD）。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（ealcitonin receptor like receptor，CRLR）、受体活性修饰蛋白（receptor activity modiying 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、RAMPl／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。

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

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 1h followed by 30 min reperfusion;the intermedin-treated group which the rats was treated by venous injection(iv) of 10-7mol/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 ventricular were measured by realtime 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(both P< 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.