背景:最新研究发现,血管紧张素Ⅱ与皮肤纤维化病变的发生和发展有关,然而有关血管紧张素Ⅱ受体在人增生性瘢痕成纤维细胞中的表达及作用鲜见报道.目的:观察血管紧张素Ⅱ 1型受体和2型受体在人增生性瘢痕成纤维细胞中的表达,并探讨它们在成纤维细胞胶原合成中的作用.设计、时间及地点:对比观察,于2006-08/2007-11在解放军广州军区广州总医院医学实验中心完成.对象:取住院患者增生性瘢痕18例,男10例,女8例,年龄19～47岁,将增生性瘢痕标本分为两组,每组各9例.正常皮肤7例,取自增生性瘢痕切除患者的正常皮肤.所有取材部位未经任何治疗,标本经无菌取材后分成2份,其中一份用40 g/L多聚甲醛固定后用于免疫组织化学检测,另一份用于成纤维细胞培养.方法:采用免疫组织化学的方法和放射性配体受体结合测定法观察人增生性瘢痕组织中成纤维细胞血管紧张素Ⅱ 1型受体和2型受体的表达,并用体外细胞培养技术观察2种受体在人增生性瘢痕成纤维细胞胶原合成中的作用.主要观察指标:2种受体在增生性瘢痕组织成纤维细胞中的表达及在人增生性瘢痕成纤维细胞胶原合成中的作用.结果:①在增生性瘢痕的成纤维细胞可见1型受体和2型受体表达,阳性染色信号较强.放射性配体受体结合测定法显示在培养的增生性瘢痕的成纤维细胞有1型受体和2型受体,受体密度分别为(10.69±2.15),(4.9±1.05)fmol/106个细胞.②在培养的人增生性瘢痕成纤维细胞,血管紧张素Ⅱ明显促进成纤维细胞胶原的合成,1 型受体阻断剂Valsartan明显抑制血管紧张素Ⅱ的这种促进作用,2型受体拮抗剂PD123319明显增强血管紧张素Ⅱ的这种作用.结论:在增生性瘢痕的成纤维细胞表达血管紧张素Ⅱ 1型受体和2型受体,血管紧张素Ⅱ通过激活2种受体对成纤维细胞胶原的合成产生相反的作用,血管紧张素Ⅱ产生和受体表达比例的变化可能影响瘢痕的形成和成熟.%BACKGROUND: It has been reported that Angiotensin Ⅱ (Ang Ⅱ) is related to occurrence and development of dermatofibrosis; however, less is explored about the expression and effect of AT1 and AT2 receptors in the fibroblasts of human hypertrophic scar.OBJECTIVE: To observe the expression of Ang Ⅱ type 1 (AT1) and type 2 (AT2) receptors in human hypertrophic scars, and explore their effects on collagen synthesis of fibroblasts.DESIGN, TIME AND SETTING: Randomized control experiment was performed at the Experimental Center, Guangzhou General Hospital of Guangzhou Military Area Command of Chinese PLA between August 2006 and November 2007. PARTICIPANTS: Samples of hypertrophic scare were taken from 18 patients (10 males and 8 females, 19-47 years Old). Seven specimens of normal skin served as control. All of the specimens collected were divided into two parts, one part for immunohistochemical staining after fixated by 4% paraformaldehyde, the other part for culturing fibroblasts.METHODS: The expression of both AT1 and AT2 receptors in fibroblasts of hypertrophic scare was detected with immunohistochemical staining and radioligand receptor binding assay. Collagen synthesis was examined in cultured fibroblasts of hypertrophic scars by measuring [3H]-proline incorporation into collagenous proteins.MAIN OUTCOME MEASURES: The expression of both AT1 and AT2 receptors in human hypertrophic scars; the [3H]-proline incorporation value in cultured fibroblasts.RESULTS: Positive staining signals of both AT1 and AT2 receptors were found in fibroblasts of hypertrophic scars. Similar results were also observed in cultured fibroblasts of hypertrophic scars, expression level of AT1 and AT2 receptors were (10.69±2.15) fmol/106 cells and (4.9±1.05) fmol/106cells, respectively. In cultured fibreblasts, Ang Ⅱ stimulation significantly increased collagen synthesis, which was inhibited by valsartan, an AT1 receptor blocker, but augmented by PD123319, an AT2 receptor antagonist.CONCLUSION: Both AT1 and AT2 receptors were expressee in the fibreblasts of hypertrophic scars, and Ang Ⅱ regulates collagen synthesis in hypertrophic scar fibroblasts through a negative cross-talk between AT1 and AT2 receptors, which might contribute, at least partly to formation and maturation of human hypertrophic scars.
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