血管紧张素Ⅱ受体2型对创面愈合过程中微血管形成的影响  

The effect of angiotensin Ⅱ type 2 receptor on angiogenesis of healing of full-thickness skin loss in mice

作　　者：熊美华[1] 李升红[2] 吴姮君[2] 唐建兵[3] 刘宏伟[2] 程飚[3] 

机构地区：[1]广州军区广州总医院医疗保健科,广东广州510010 [2]广东省暨南大学第一附属医院整形外科,广东广州510630 [3]广州军区广州总医院整形外科,全军热区损伤救治与组织修复重点实验室,广东广州510010

出　　处：《感染．炎症．修复》2013年第4期217-220,I0001,共5页Infection Inflammation Repair

基　　金：全军医学科学技术研究"十一五"计划科技攻关项目(08G027);广州市科技计划项目(2012J4100044)

摘　　要：目的:观察血管紧张素Ⅱ受体2型(AT2R)在创面肉芽组织微血管形成中的作用,探讨其影响新血管形成的可能机制。方法:用打孔器在小鼠背部制成直径6.0 mm全层皮肤缺损创面模型,将24只C57BL/6J小鼠分成两组(n=12):PD123319处理组腹腔注射特异性AT2R阻断剂PD123319(10 mg·kg^(-1)·d^(-1)),对照组腹腔注射等量生理盐水。分别在创面形成后第3、5、7、和14天取创面组织标本,每个时间点3只小鼠。另有6只作为正常对照。采用HE染色观察肉芽组织和新血管形成的情况,应用ELISA法检测创面愈合过程中创面局部组织血管内皮生长因子受体1(VEGFR1)的变化,免疫组织化学方法检测正常小鼠皮肤与创面愈合过程中创面局部组织AT2R的表达情况。结果:正常小鼠皮肤AT2R在整个表皮层均有阳性表达,在真皮层,AT2R在微血管内皮细胞,皮肤附件如毛囊、汗腺、皮脂腺有阳性表达。在小鼠全层皮肤缺损创面愈合过程中,创面局部组织AT2R产生逐渐增加,第7天达到峰值,以后逐渐下降。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)mm^2和(7.15±0.42)mm^2,PD123319处理组创面肉芽组织面积分别为(11.51±0.98)mm^2和(9.32±0.67)mm^2,两组间差异有统计学意义(P<0.05)。PD123319可随时间的延长明显增加肉芽组织中VEGFR1的表达和血管形成的组织学评分,在第7天达到峰值,两组间差异有显著性(P<0.05),然后均逐渐下降。结论:在创面愈合过程中,AT2R可能参与创面的愈合及其后期的塑性改建,并通过调节VEGFR1水平影响肉芽组织中微血管的形成。Objective：To observe the effect of angiotensin II （ Ang II） type 2 receptor （AT2R） on angiogenesis in granulation tissue, and to explore the possible mechanism of AT2R in influencing neovascularization in wound healing. Methods：Full-thickness circular skin defects of 6.0 mm in diameter were created on the dorsum of 24 C57BL/6J mice, and they were divided randomly into two groups（n= 12） . mice of one group were given peritoneal injection of AT2R blocker PD123319 （ 10 mg/kg daily）, and another group treated with normal saline after woun- ding. Another group of six mice served as normal control group. Specimens were harvested from the wounds of each mouse on days 3, 5, 7 and 14 after wounding, Granulation tissue formation and neovascularization in the wounded skin tissues were evaluated after HE staining. The expression of vascular endothelial growth factor receptor 1 （VEGFR 1） in wounded tissues during the healing process was detected by ELISA. The localization and expression of AT2R in normal mouse skin tissue and wound tissue were studied with immunohistochemistry. Results： In normal mouse skin, AT2R was expressed throughout the epidermis, AT2R positive cells were found in microvascular endothelial cell in the dermis, and skin appendages including hair follicles, sweat glands, sebaceous glands. In the process of healing, AT2R was found to be increased gradually in local tissue, reaching the peak on ？th day, and then it gradually declined. Treatment with PD123319 significantly increased the number of neovascularization and the amount of granulation tissue compared with that of control group at 5 days and 7 days after wounding. Area of granulation tissue in the control group was （9.37±0. 53） mxn2 on day 5 on （7. 15±0. 42） mrn2 on day 7 after injury. Granulation tissue area in PD123319 treated group was （11.51±0.98） mm2 and （9.32±0.67） mm2 respectively, and the difference was statistically significant （P〈0.05）. Application of PD123319 increased the expression of

关 键 词：血管紧张素Ⅱ受体 创面愈合 生长因子 血管形成 

分 类 号：R541.75[医药卫生—心血管疾病]