肾上腺髓质素对新生大鼠缺氧缺血再灌注性脑损伤的保护作用

Neuroprotection effects of exogenous adrenomedullin against hypoxic-ischemia reperfusion brain damage in neonatal rats

目的:观察外源性肾上腺髓质素(ad-renomedullin,AM)对新生大鼠缺氧缺血再灌注性脑损伤(hypoxic-ischenmia reperfusion brain damage,HIRBD)的保护作用。方法:40只7日龄SD新生大鼠随机分为正常对照组、缺氧缺血再灌注(HIR)组、AM干预组(缺氧缺血后即刻0、6、12h分别给于AM腹腔注射,1.0mg/kg),每组8只,于术后48h处死。取耳间线前2mm水平做冠状位脑组织切片,观察脑组织病理学变化,同时检测脑组织匀浆一氧化氮合酶(NOS)、谷胱甘肽(GSH)、髓过氧化物酶(MPO)的含量。结果:HIR、AM12h干预组新生大鼠脑病理改变明显,AM0、6h干预组的脑病理改变明显减轻。AM0、6h干预组脑组织中结构型一氧化氮合酶(cNOS)、GSH的水平较HIR组显著增高,而诱导型一氧化氮合酶(iN-OS)、MPO的水平较HIR组显著降低。结论:缺氧缺血再灌注后0～6h予外源性AM干预对新生大鼠HIRBD有不同程度的保护作用,这种作用与其增加体内抗氧化物质GSH的活性、NO的释放及抑制中性粒细胞对脑组织的浸润有关。

AIM： To observe the neuroprotection effects exogenous adrenomedullin （ AM ） against hypoxic-ischemia reperfusion damage （HIRBD） in neonatal rat models. METHODS： Forty neonatal rats were randomly divided into Control Group （ n = 8, with sham operation ）, Hypoxic-ischemia Reperfusion （HIR） Group and Intervention Group （ n = 8, wth intraperitoneal AM injection 0, 6 and 12 h after making model）. All rats were decapitated at 48 hours after reperfusion, and the cerebral slices were made at the 2 mm level in front of the interaural line. The pathobiological changes of brain tissue were observed by themethod of HE dye in light microscope, and the levels of nitrogen monoxide synthase （NOS）, glutathion （GSH） and myeloperoxidase （MPO） in neonatal rats cerebral tissue were determined by using chromatometry. RESULTS： Hypoxic-ischemia reperfusion could induce obviously cerebral pathological change which could be improved by AM. The brain tissue levels of cNOS and GSH in AM 0 and 6 h Group were significantly higher than those of HIR Group （ P 〈 0.05）. The brain tissue levels of iNOS and MPO in AM 0,6 h Group were significantly lower than those of HIR Group （ P 〈 0.05）. CONCLUSION： The exogenous AM given 0 - 6 h after hypoxic-ischemia may protect the neonatal rats from HIRBD by enhancing GSH activities and the release of NO, checking the infiltration of neutrophile granulocyte into cerebral tissues.