血管紧张素Ⅱ2型受体阻滞剂对小鼠全层皮肤缺损创面愈合的影响

摘要

目的:观察阻断血管紧张素Ⅱ (Ang Ⅱ)及其2型受体(AT2R)对创面愈合过程的创面愈合率、上皮爬行、肉芽组织形成以及创伤局部生长因子表达的影响,探讨Ang Ⅱ及AT2R影响创伤愈合的机制.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注射给予特异性AT2R阻断剂PD123319(每天10mg/kg),于创面形成后第3、5、7、9、11、13和15天切取创面组织标本,采用HE染色观察PD123319对创面愈合过程中创面愈合率、上皮爬行和肉芽组织生长的影响；采用ELISA法检测PD123319对创面内与创伤愈合密切相关的表皮生长因子(EGF)、血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)表达的影响.结果:对照组在创面形成后第5天和第7天的愈合率分别为(63.55±2.57)％和(80.78 +4.65)％.PD123319处理组在创面形成后第5天和第7天分别为(79.89 +4.56)％和(88.98 +3.83)％,两组差异有统计学意义(P＜0.05).在伤后第5天和第7天,对照组创面上皮爬行距离分别为(1.22±0.15)mmm和(1.93±0.17)mm,PD123319处理组创面上皮爬行距离分别为(1.65±0.12)mm和(2.36 ±0.18) mm,两组差异有统计学意义(P＜0.05).在伤后第5天和第7天对照组创面肉芽组织的面积分别为(9.37±0.53)mm2和(7.15 +0.42)mm2,PD123319处理组创面肉芽组织面积分别为(11.51 +0.98) mm2和(9.32±0.67) mm2,两组差异有统计学意义(P＜0.05).在伤后第5天和第7天,PD123319处理组创面局部EGF、VEGF和bFGF的含量明显高于对照组,差异有统计学意义(P＜0.05).结论:AT2R阻滞剂PD123319能够促进创面愈合.PD123319促进创面愈合可能与其促进创面内上皮爬行、肉芽组织形成及EGF、VEGF、bFGF等生长因子的表达有关.%AIM:To observe the effect of angiotensin Ⅱ (Ang Ⅱ) and its type 2 receptor (AT2R) on re-epi-thelialization,granulation tissue formation and growth factor production during wound healing,and to explore the possible mechanism by which Ang Ⅱ and AT2R influence wound healing.METHODS:Two full-thickness skin wounds were created on the dorsum of C57BL/6J mice.The animals were treated with or without AT2R blocker PD123319 at a dose of 10mg/kg daily after wounding.Specimens were taken from the wound of each mouse on days 3,5,7,9,11,13 and 15 after wounding.Re-epithelialization and granulation tissue formation in the wounded skin tissues were evaluated by HE staining.The production of growth factors,epidermal growth factor (EGF),vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in wounded tissues during the healing process was detected by ELISA.RESULTS:Treatment with PD123319 significantly increased the rate of re-epithelialization and the area of granulation tissue compared with control group at 5 d and 7 d after wounding.Moreover,peritoneal application of PD123319 increased the production of EGF,VEGF and bFGF in the wounded tissues at the indicated time points after wounding.CONCLUSION:AT2R blocker PD123319 accelerates wound healing via promoting re-epithelialization,granulation tissue formation and growth factor production.