α-黑素细胞刺激素对大鼠局灶脑缺血再灌注后炎症反应的影响(英文)

Effect of alpha-melanophore-stimulating hormone on inflammatory reaction following focal cerebral ischemia-reperfusion in rats

背景:研究表明,神经免疫调节肽α-黑素细胞刺激素(α-melanophore-stimulatinghormone,α-MSH)可通过抑制促炎因子释放、改善淋巴细胞活力等途径发挥其抗炎、抗菌、退热和免疫调节作用,在防治全身炎性反应综合征中可能有良好的应用前景。目的:研究α-MSH对缺血-再灌注后脑组织炎性细胞浸润及黏附分子(intercellularadhesionmolecule,ICAM-1)表达的影响。设计:随机双盲对照实验。单位:解放军第三军医大学西南医院急救部。材料:健康雄性Wistar大鼠60只,由第三军医大学实验动物中心提供。实验分3组,即假手术组、缺血组和α-MSH治疗组,每组根据缺血2h后再灌注6,12,24,48,72h5个时相点分为5组,每组各时相点4只。干预:制备大脑中动脉闭塞模型,在每个时间点取2只动物用免疫组织化学方法检测ICAM-1的表达情况。各时间点取2只动物用于检测髓过氧化物酶(myeloperoxidase,MPO)活性。在透射电镜下观察脑组织细胞超微结构。主要观察指标:ICAM-1阳性表达,MPO活性,细胞超微结构。结果:缺血再灌注后高倍镜下(×200)每平方毫米大鼠脑组织切片的I-CAM-1阳性细胞数在假手术组中稳定于(1.02±0.14)～(1.15±0.16)个/mm2;缺血组6h后ICAM-1开始上升,于12h达高峰,由(2.82±0.07)个/mm2增至(7.08±0.09)个/mm2。

BACKGROUND:It has been indicated that neuro immuno modulation peptide,α melanophore stimulating hormone(α MSH),can play an effective role in anti inflammation,antibiosis,defervescence and immunological regulation through inhibiting the release of proinflammatory factor,improving the vigor of lymphocyte and other ways,so that it has a good prospect in the prevention and treatment of systemic inflammatory response syndrome. OBJECTIVE:To study the influence of α MSH on the infiltration of cerebral inflammatory cell and the expression of intercellular adhesion molecule(ICAM 1) following ischemia reperfusion. DESIGN:Randomly double blind and control experiment. SETTING:Emergency Department of Southwest Hospital of the Third Military Medical University of Chinese PLA. MATERIALS:Sixty healthy male Wistar rats provided by Animal Center of the Third Military Medical University of Chinese PLA, were divided into three groups including sham operated group, ischemia group and α MSH treated group, and each group was divided into five subgroups according to reperfusion for 6,12,24,48,72 hours after ischemia of 2 hours with 4 rats per phase in each group. INTERVENTIONS:Models of middle cerebral artery occlusion were prepared.Two rats were detected for the expression of ICAM 1 in each phase with immunohistochemical method.And two rats were detected for the activity of myeloperoxidase(MPO) in each phase. Ultrastructures of brain tissue cells were observed with transmission electron microscope. MAIN OUTCOME MEARSURES:Positive expression of ICAM 1, MPO activity and cellular ultrastructure. RESULTS:Positive expression cell population of ICAM 1 per square millimeter in brain tissue slice of rats under high power lens(×200) after ischemia reperfusion was stable at(1.02±0.14)-(1.15±0.16)/mm2 in sham operated group,which began to increase after 6 hours in ischemia higher than that of the sham operated group while ICAM 1 expression was significantly down regulated in α MSH treatment group form(4.51±0.11)/mm2 to(2.97±0.09)/mm2.MPO activity in brain was stable at(3.17±0.27)-(3.67±0.23) nkat in sham operated group, which began to increase at 12 hours in ischemia group,and reached peak level at 24 hours from(5.83 ±0.15) nkat to(9.00±0.25) nkat,then continued to rise at 72 hours while MPO activity was reduced much more in α MSH treatment group than in ischemia group, and was(6.63±0.27) nkat at 24 hours.Ultrastructure observation showed that neuron was integrated in sham operated group,while nerve cellular membrane,colloid cellular membrane,and karyotheca reperfusion were damaged,mitochondrion was swollen,and ultrastructure changes reached the peak level at 12 hours in ischemia group.This was similar in the treatment group of the early stage but did not aggravated following the phase after 12 hours. CONCLUSION:α MSH can lessen the infiltration of cerebral inflammatory cell and ICAM 1 expression following ischemia reperfusion and has protective effects on cerebral ischemia reperfusion damage.