Hairless基因敲除小鼠发生炎性衰老的可能机制

The possible mechanism of inflammatory aging in Hairless gene knockout mice

目的探讨Hairless基因敲除形成的无毛小鼠发生早期衰老的可能机制。方法分别选用雄性野生型C57/BL6J小鼠和雄性Hairless基因敲除无毛小鼠,每组小鼠为12只,均为6月龄。通过小鼠皮肤形态观察,苏木素-伊红(HE)染色观察皮肤组织病理学特征,水迷宫行为学实验和力竭跑步实验分别检测两组学习记忆能力和运动能力的变化,酶联免疫吸附试验(ELISA)检测血清中白细胞介素(IL)-6、IL-1β、肿瘤坏死因子(TNF)-α水平及背部皮肤中超氧化物歧化酶(SOD)和丙二醛(MDA)表达水平,实时荧光定量-聚合酶链反应(qRT-PCR)检测皮肤组织中弹性蛋白原(tropoelastin)和纤维蛋白(fibrillin)-1基因mRNA表达水平。结果与野生型小鼠相比,无毛小鼠皮肤褶皱明显,皮肤组织中有炎性细胞浸润,且胶原纤维基因表达水平显著下调,血清中炎性因子明显升高,其学习记忆能力和力竭运动能力变弱。结论Hairless基因敲除形成的无毛小鼠在皮肤、学习记忆能力和运动能力方面均发生衰退,其机制可能与炎症有关。

Objective To explore the possible mechanism of early aging in hairless mice formed by Hairless gene knockout.Methods Male wild-type C57/BL6J mice and male Hairless gene knockout hairless mice were selected,respectively.There were 12 mice in each group,all of which were 6 months old.The skin morphology was observed and histopathological characteristic was observed by hematoxylin-eosin(HE)staining.Water maze behavioral experiment and exhaustive running experiment were used to detect the changes of learning and memory ability and motor ability of the two groups,respectively.The levels of interleukin(IL)-6,IL-1βand tumor necrosis factor(TNF)-αin serum and the expression levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in back skin were detected by enzyme-linked immunosorbent assay(ELISA).Real-time fluorescence quantification-polymerase chain reaction(qRT-PCR)was used to detect the mRNA expression levels of tropoelastin and fibrillin-1 genes in skin tissues.Results Compared with wild-type mice,hairless mice had obvious skin folds,inflammatory cell infiltration in skin tissue,the expression level of collagen fiber gene was significantly down-regulated,inflammatory factors in serum was significantly increased,its learning and memory ability and exhaustive exercise ability were weakened.Conclusions The skin,learning and memory ability and motor ability of hairless gene knockout hairless mice were all decreased and its mechanism might be related to inflammation.