血管紧张素Ⅱ受体在人不稳定性瘢痕溃疡中的表达

Expression of angiotensin Ⅱ receptors in dermal ulcer of human unstable scars

目的:观察血管紧张素Ⅱ1型受体和2型受体在人正常皮肤、不稳定性瘢痕和溃疡中的表达特征与规律,探讨其与不稳定性瘢痕溃疡形成的关系。方法:选择2004-09/2005-06解放军广州军区广州总医院整形外科收治不稳定性瘢痕所致溃疡患者7例。取溃疡中心、溃疡边缘、周边的不稳定瘢痕及正常皮肤组织标本,经无菌取材后分成两份,其中1份经体积分数为0.1的中性甲醛固定后,用于光镜形态学观察。另1份经40g/L多聚甲醛固定后采用免疫组织化学方法检测血管紧张素Ⅱ1型和2型受体在不稳定性瘢痕溃疡和正常皮肤组织中的表达和分布熏并采用HPIAS-1000高清晰度彩色病理图文报告管理系统对血管紧张素Ⅱ1型和2型受体在观察部位的表达进行定量分析,每张切片随机选5个高倍镜视野(×400),测定每个视野下阳性反应的平均吸光度。结果:①在正常皮肤中,血管紧张素Ⅱ1型和2型受体主要分布于表皮角质形成细胞、真皮毛细血管、皮肤附件包括毛囊和汗腺。②在不稳定性瘢痕内表皮细胞血管紧张素Ⅱ1型和2型受体均有强阳性表达,成纤维细胞和微血管内皮细胞亦可见较强阳性染色;在溃疡边缘血管紧张素Ⅱ1型受体阳性染色信号在爬行的上皮缘较弱,血管紧张素Ⅱ2型受体表达持续增强。在溃疡中心的肉芽组织微血管内皮细胞及成纤维细胞中,尽管血管紧张素Ⅱ1型受体有表达,但阳性反应较弱;血管紧张素Ⅱ2型受体的阳性染色信号仍较强。③血管紧张素Ⅱ1型受体蛋白的平均吸光度(A)在不稳定性瘢痕条件下升高,在溃疡条件下下降穴正常皮肤、不稳定性瘢痕、溃疡边缘、溃疡中心分别为0.1829±0.0212,0.6894±0.0752,0.2132±0.0896,0.1978±0.0215,P<0.05雪。血管紧张素Ⅱ2型受体在正常皮肤中仅有较弱的阳性表达,不稳定性瘢痕、溃疡边缘、溃疡中心表达明显高于正常穴分别为0.1293±0.0117,0.5698±0.0649,0.6945±0.0968,0.4732±0.0527,P<0.05雪。结论:血管紧张素Ⅱ受体1型和2型在不稳定性瘢痕溃疡组织中表达和分布的不同变化规律提示,血管紧张素Ⅱ可能通过血管紧张素Ⅱ1型和2型受体参与不稳定性瘢痕溃疡的形成,进一步研究血管紧张素Ⅱ在这个过程中的作用及其受体血管紧张素Ⅱ1型和2型介导的信号传递通路将有助于理解不稳定性瘢痕发生溃疡和溃疡发生后难以愈合的机制。

AIM： To observe the expression and distribution of angiotensin H （Ang Ⅱ ） type 1 （AT1） and type 2 （AT2） receptors in human normal skin, unstable scars and chronic dermal ulcers, and explore the relation with the formation of unstable scars ulcers. METHODS：From September 2004 to June 2005, seven inpatients with ulcer resulting from unstable scars in Department of Plastic Surgery, Guangzhou General Hospital of Guangzhou Military Area Command of Chinese PLA were selected for the present study. The samples of normal skin, unstable hypertrophic scars and chronic ulcer were got and divided into two parts： one part was used for observing the morphological characteristics after being fixed with neutral formaldehyde of the volume fraction of 0.1, other one was used for detecting the expression of both AT1 and AT2 receptors in unstable scar ulcer and normal skin tissue with method after being fixed with 40 g/L citromint. HPIAS-1000 high power color imaging analysis system was used for determining the intensity of the expression of beth AT1 and AT2 receptors. Five high-power views （x400） of each section were selected randomly for calculating the abserbance （A） of positive reaction. RESULTS： ①In normal skin, the expression of beth AT1 and AT2 receptors was mainly located in epidermal keratinocytes, dermal vessel walls, and hair follicles as well as sweat glands. ②In unstable scars and chronic ulcer, both AT1 and AT2 receptors showed positive expression in epidermic cells, and also in fibroblasts and endothelial cell of microvessel. AT1 receptor expression was weaker in chronic ulcer, while AT2 receptor greatly expressed in chronic ulcer. In the endothelial cells and fibroblasts of microvessel of granulation tissue of ulcer center, although there was expression of AT1, but positive reaction was weak. Positive staining of AT2 receptor was strong. ③ Mean A of AT1 receptor protein increased in unstable scar, and decreased in ulcer [It was 0.182 9±0.021 2,0.689 4±0.075 2,0.213 2±0.089 6,0.197 8±0.021 5 ,P 〈 0.05, in normal skin, unstable scar, and the periphery and center of chronic ulcer, respectively].There was weak positive expression of AT2 receptor in normal skin, and the expressions in unstable scar, and the periphery an.d center of chronic ulcer were higher significantly than that of normal [It was 0,129 3±0.011 7, 0.569 8 ±0.064 9,0.694 5±0.096 8,0.473 2±0.052 7,P 〈 0.05, respectively]. CONCLUSION： The different changes of expression and distribution of AT1 and AT2 in unstable scar and ulcer indicate that Ang Ⅱ can join the formation of unstable scar and ulcer by AT1 and AT2 reeeptors. Further studying the role and signaling mechanisms of both AT1 and AT2 receptors might assist in improving clinical management of wound.