阻滞血管紧张素Ⅱ1型受体对创面愈合的影响

Effect of blocking angiotensin lI type 1 receptor on wound healing in mouse skin full-thickness injury model

目的观察阻断血管紧张素Ⅱ（AngⅡ）1型受体（ATlR）对创面愈合过程的上皮爬行、肉芽组织形成以及创伤局部生长因子产生的影响，探讨AngⅡ及ATlR影响创伤愈合的分子机制。方法建立小鼠背部全层皮肤缺损创面模型，直径6mm，在创面模型建立同时腹腔给予ATlR阻断剂Losartan（每天20mg／kg），在创面形成后第3、5、7、9、11、13、15天切取创面组织标本，采用苏木素．伊红（HE）染色观察ATlR阻断剂Losartan对创面愈合过程中上皮爬行和肉芽组织生长的影响；采用酶联免疫吸附试验（ELISA）法检测ATIR阻断剂Losartan对与创面愈合密切相关的表皮生长因子（EGF）、血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）产生的影响。结果对照组创面愈合率在伤后第5、7天分别为（63．55±2．57）％、（80．78±4．65）％。Losartan处理组创面愈合率在伤后第5、7天创面愈合率分别为（47．82±4．08）％、（65．05±9．18）％，两组差异有统计学意义（P〈0．05）。在伤后第5、7天对照组创面上皮爬行距离分别为（1．22±0．15）mm、（1．93±0．17）mm，Losartan处理组创面上皮爬行距离分别为（0．75±0．16）mm、（1．49±0．14）mm，两组差异有统计学意义（P〈0．05）。在伤后第5、7天对照组创面肉芽组织的面积分别为（9．37±0．53）mm2、（7．15±0．42）mm2，Losartan处理组创面肉芽组织面积分别为（6．92±0．49）mm2、（4．91±0．35）mm2，两组差异有统计学意义（P〈0．05）。在伤后第5、7天Losartan处理组创面局部EC．F、VEGF、bFGF含量明显低于对照组，两组差异有统计学意义（P〈0．05）。结论AT1R阻断剂抑制了创面的上皮化、肉芽组织的形成和创面局部生长因子的产生，因而延缓了创面愈合的速度。

Objective To observe the effect ofangiotensin Ⅱ （Ang Ⅱ ） type 1 receptor （AT1R） on reepitheliazation, granulation tissue formation and growth factor production during wound healing, and explore the possible mechanism by which Ang Ⅱ influenced wound healing. Methods Two full-thickness skin wounds were created on the dorsum of C57/BL6J mice. Animals were treated with or without AT1R blocker, Losartan at a close of 20 mg/kg daily after wounding. Specimens were taken from the wound of each mouse on the clay 3, 5, 7, 9, 11, 13 and 15 after wounding. Reepitheliazation and granulation tissue formation in wounded skin tissue were evaluated by hematoxylin and eosin （HE） staining. The production of growth factors in wounded tissue during the healing process was detected by using enzyme linked immu- nosorbent assay （ELISA）. Results Treatment with AT1R blocker, Losartan, significantly inhibited the rate of reepithelialization and the thickness of granulation tissue as compared with Untreated group at the day 5 and 7 after wounding. Moreover, peritoneal application of Losartan decreased the production of epidermal growth factor （EGF）, vascular endothelial growth factor （VEGF） and basic fibroblast growth factor （LFGF） in the wounded tissues at the indicated time after wounding. Conclusion These results indicate that AT1R blocker impaired wound healing at least partially via inhibiting growth factors production.