驻极体联合5-氟尿嘧啶对瘢痕形成中TGF-β/MMPs通道的影响  

Effect of electret combined with 5-fluorouracil on TGF-β/MMPs pathway during scar formation

作　　者：郭鑫 涂晔 苑旺 梁媛媛 江键 崔黎丽[4] GUO Xin;TU Ye;YUAN Wang;LIANG Yuanyuan;JIANG Jian;CUI Lili(Department of Physics and Mathematics,Faculty of Health Service,the Second Military Medical University,Shanghai 200433,China;Shanghai East Hospital,Shanghai 200120,China;General Hospital of Northern Theater,Shenyang 110000,China;Department of Inorganic Chemistry,School of Pharmacy,the Second Military Medical University,Shanghai 200433,China)

机构地区：[1]海军军医大学卫生勤务学系数理教研室,上海200433 [2]上海东方医院,上海200120 [3]北部战区总医院,辽宁沈阳110000 [4]海军军医大学药学院无机化学教研室,上海200433

出　　处：《中国医学物理学杂志》2020年第9期1193-1197,共5页Chinese Journal of Medical Physics

基　　金：国家自然科学基金(51477175);上海市卫计委青年科学基金(20164Y0051)。

摘　　要：目的:研究驻极体联合5-氟尿嘧啶(5-Fu)对瘢痕生长的抑制作用及其相关的作用机制。方法:将驻极体贴剂、5-Fu贴剂、驻极体联合5-Fu贴剂分别作用于大鼠创伤创面愈合的瘢痕形成过程,通过对创面组织瘢痕增生指数、显微结构以及组织中TGF-β、MMP1、TIMP1和MMP2含量情况的检测,研究驻极体以及驻极体与5-Fu联合对瘢痕形成的抑制作用及作用机制。结果:(1)驻极体、5-Fu以及驻极体联合5-Fu贴剂均能有效抑制瘢痕的形成和生长。三者分别作用创面4周后,瘢痕增生指数依次是对照组的85.8%、85.1%和64.9%(P<0.05)。(2)驻极体、5-Fu以及驻极体与5-Fu联合均能影响瘢痕形成中的TGF-β/MMPs通路。表现为三者均能抑制TGF-β的表达,上调MMP1的表达,增加MMP1/TIMP1比例,下调MMP2表达。并且作用效果为驻极体联合5-Fu>5-Fu>驻极体。结论:与5-Fu一样,驻极体也能抑制瘢痕组织的生长,且两者具有协同作用;它们的作用机制与瘢痕组织内TGF-β、MMP1、TIMP1和MMP2的表达有关;驻极体与5-Fu联用后,在相同治疗效果的基础上,可减少5-Fu的剂量,降低它的毒副作用。Objective To investigate the inhibiting effect of electret combined with 5-fluorouracil(5-Fu)on scar formation and discuss the related mechanisms.Methods Different patches,including electret,5-Fu,and electret combined with 5-Fu,were separately applied to the wound in mice,participating in the formation of hypertrophic scar.The scar hyperplasia index and microstructure of wound tissues and the expressions of TGF-β,MMP1,TIMP1 andMMP2 in tissues were detected for studying the inhibiting effect of electret combined with 5-Fu on scar formation and discussing the related mechanisms.Results(1)The formation and growth of scar were effectively inhibited by electret,5-Fu,and electret combined with 5-Fu,separately.After 4 weeks of treatments by different patches,the scar hyperplasia index was decreased to 85.8%,85.1% and 64.9% of that in control group,respectively(P<0.05).(2)All the treatments(electret,5-Fu,and electret combined with 5-Fu)had effects on TGF-β/MMPs pathway during scar formation.In treatment groups,TGF-βexpression was inhibited;and MMP1 expression was up-regulated;and MMP1/TIMP1 ratio was increased;whereas MMP2 was down-regulated.The effect of electret combined 5-Fu group was better than that of 5-Fu,followed by electret.Conclusion Like 5-Fu,electret can inhibit the growth of scar,and they have a synergistic effect.The mechanism may be related to the expressions of TGF-β,MMP1,TIMP1 and MMP2.The electret combined with 5-Fu is expected to improve the bioavailability of 5-Fu(reduce 5-Fu dose and decrease its toxic effects)on the basis of achieving the same therapeutic effect.

关 键 词：增生性瘢痕 5-氟尿嘧啶 驻极体 转化生长因子-Β 基质金属蛋白酶 

分 类 号：R318[医药卫生—生物医学工程] R34[医药卫生—基础医学]