肾上腺髓质素真核表达载体对皮瓣缺血再灌注损伤的影响

Effects of adrenomedullin eukaryotic expression vector on skin flap ischemia reperfusion injury

背景:肾上腺髓质素可在心、脑、肾、肝等器官的缺血再灌注过程中起保护作用。目的:观察肾上腺髓质素真核表达载体对大鼠腹部皮瓣缺血再灌注损伤的影响及其作用机制。方法:构建大鼠肾上腺髓质素真核表达载体,将SD大鼠随机分假手术组、模型组、维拉帕米组、重组质粒组。重组质粒组腹部皮内注射肾上腺髓质素真核表达载体,其余各组注射等量生理盐水,各组注射4次后建立缺血再灌注模型,维拉帕米组于皮瓣内注射维拉帕米。结果与结论:与模型组相比,重组质粒组皮瓣组织中丙二醛、血管内皮素1的含量分别降低了38.50%(P<0.01),54.73%(P<0.01),超氧化物歧化酶的含量增加了50.67%(P<0.05)。皮瓣组织学检查结果显示重组质粒组皮瓣炎性细胞浸润与水肿程度也较模型组明显减轻。结果证实肾上腺髓质素真核表达载体对大鼠皮瓣缺血再灌注损伤具有保护作用,其机制与减轻脂质过氧化及减少炎症细胞浸润有关。

BACKGROUND：Adrenomedullin plays protective effects on ischemia and reperfusion injury of the heart, brain, kidney and liver. OBJECTIVE：To explore the effects of adrenomedullin eukaryotic expression vector pVAX1-ADM on ischemia reperfusion injury in rat abdominal flaps and the possible mechanism of action. METHODS：Rat adrenomedullin eukaryotic expression vector pVAX1-ADM was reconstructed. Rats were randomly divided into four groups：sham-operated, model, Verapamil, and pVAX1-ADM. Rats in the pVAX1-ADM group were injected with recombinant plasmid （600 μg） and rats in the other three groups were injected with the same amount of normal saline, once a week. Four weeks later, ischemia reperfusion models were established by 9 hours of ischemia followed by 12 hours of reperfusion. Before reperfusion, the Verapamil group was injected with Verapamil. At 7 days after surgery, the contents of malondialdehyde （MDA）, superoxide dismutase （SOD） and endothelium 1 （ET-1） in targeted flaps were measured, and histomorphological examination of the targeted flaps was performed. RESULTS AND CONCLUSION： Compared with the model group, the content of MDA and ET-1 in the pVAX1-ADM group abdominal flaps was decreased by 38.50% （P 0.01） and 54.73% （P 0.01） respectively, and activity of SOD was increased by 50.67% （P 0.05）. Compared with the model group, only a few inflammatory cells infiltrated and interstitial edema decreased significantly in the flaps in the PVAX1-ADM group. These findings suggest that adrenomedullin eukaryotic expression vector PVAX1-ADM exhibits protective effects on skin flap ischemia reperfusion injury, and the underlying mechanism is related to reduction in lipid peroxidation and inflammatory cell infiltration.