吡咯喹啉醌对Bmi-1基因缺失引起小鼠皮肤早衰的保护作用
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湖南省教育厅青年科学研究项目(14B141)


Protective effect of pyrroloquinoline quinone on premature aging of skin in Bmi-1 knockout mice
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    摘要:

    目的:研究吡咯喹啉醌(pyrroloquinoline quinone,PQQ)是否通过抑制氧化应激发挥对Bmi-1缺失小鼠引起皮肤早衰的治疗作用。方法:将同窝的Bmi-1杂合子(Bmi-1+/-)雌雄小鼠进行配对,取7周龄正常饮食野生型(wild type,WT)小鼠10只,正常饮食Bmi-1基因敲除(Bmi-1 knock out,BKO)小鼠10只,以及正常饮食添加PQQ 的BKO小鼠(PQQ+BKO)10只,利用HE染色、组织化学、免疫组织化学及流式细胞仪检测等方法进行相关实验。结果:与BKO组小鼠比较,PQQ+BKO组小鼠整体表型部分纠正,毛色光滑,体重增加,生存期明显延长;PQQ+BKO组小鼠皮肤厚度[(142.65±0.25)μm]与BKO组小鼠[(78.45±0.35)μm]相比,差异有统计学意义(P<0.01);PQQ+BKO组小鼠皮肤总胶原阳性面积百分比[(25.64±0.28)%]与BKO组小鼠[(14.87±0.47)%]相比,差异有统计学意义(P<0.01);PQQ+BKO组小鼠皮肤PCNA阳性细胞百分比[(18.54±0.37)%]与BKO组小鼠[(5.85±0.64)%]相比,差异有统计学意义(P<0.01);PQQ+BKO组小鼠皮肤纤维化阳性面积百分比[(48.64±0.28)%]与BKO组小鼠[(87.64±0.46)%]相比,差异有统计学意义(P<0.01); PQQ+BKO组小鼠皮肤的ROS水平(298.17±0.25)较BKO组小鼠(427.80±0.63)显著下降(P<0.01)。结论:PQQ通过增加皮肤胶原蛋白、促进皮肤细胞增殖、减少皮肤组织纤维化、清除氧自由基ROS水平等对Bmi-1缺失所致皮肤早衰发挥保护作用。

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    Objective:To investigate whether pyrroloquinoline quinone(PQQ) plays a treatment role in premature aging of skin in Bmi1-/- mice by inhibiting oxidative stress. Methods:We paired with littermates Bmi-1+/- between male and female mice,and selected the mice at the age of 7 weeks:wild type mice and normal diet (10 mice),Bmi1-/- mice and normal diet (10 mice),Bmi1-/- mice and add PQQ diet (10 mice). HE staining,histochemistry,immunohistochemistry,and flow cytometry were peformed. Results:Compared with BKO mice,PQQ partially rescued total body phenotype,made hair of skin smooth,increased body weight and prolonged survival time. Compared skin thickness of PQQ+BKO mice [(142.65±0.25)μm] to BKO mice [(78.45±0.35)μm],the difference was statistically significant (P<0.01). The percentage of total collagen positive area of skin in the PQQ+BKO group [(25.64±0.28)%] was significantly different from that in the BKO group [(14.87±0.47)%,P<0.01]. The percentage of skin PCNA positive cells in the PQQ+BKO group [(18.54±0.37)%] was significantly different from that in the BKO group [(5.85±0.64)%,P<0.01]. The positive area of skin fibrosis in the PQQ+BKO group [(48.64±0.28)%] was significantly different from that in the BKO group [(87.64±0.46)%,P<0.01]. Compared with BKO mice (427.80±0.63),the levels of ROS in the skin of the PQQ+BKO group (298.17±0.25) were significantly decreased,and the difference was statistically significant(P<0.01). Conclusion:The results of these studies indicated that PQQ played a role in protecting premature aging of skin induced by Bmi-1 defection through multiple aspects,such as promoting skin cell proliferation,reducing skin tissue fibrosis,scavenging ROS levels of oxygen free radical.

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黄元清,苗登顺,陈 宁.吡咯喹啉醌对Bmi-1基因缺失引起小鼠皮肤早衰的保护作用[J].南京医科大学学报(自然科学版),2017,(6):691-696

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  • 收稿日期:2016-09-21
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  • 在线发布日期: 2017-06-30
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