血管紧张素Ⅱ受体在增生性瘢痕成纤维细胞增殖中的作用

目的观察血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)Ⅰ型(angiotensinⅡtype1,AT1)和Ⅱ型(angiotensinⅡtype2,AT2)受体在人增生性瘢痕成纤维细胞增殖中的作用。方法体外培养人增生性瘢痕成纤维细胞,用免疫组织化学方法检测正常皮肤和增生性瘢痕组织标本AngⅡ受体的表达,用逆转录-多聚酶链式反应(RT-PCR)和放射性配体受体结合测定法检测增生性瘢痕成纤维细胞AngⅡ受体的表达,用3H-TdR的掺入法检测AngⅡ对成纤维细胞增殖的影响。结果增生性瘢痕组织的成纤维细胞可见AT1和AT2受体表达,阳性染色信号较正常皮肤增强。放射性配体受体结合测定法显示在培养的增生性瘢痕成纤维细胞AT1和AT2受体密度分别为(10.69±2.15)fmol/106个细胞,(4.9±1.05)fmol/106个细胞。RT-PCR结果显示培养的人增生性瘢痕成纤维细胞表达AT1和AT2受体。在培养的人增生性瘢痕成纤维细胞,AngⅡ明显促进成纤维细胞3H-TdR的掺入率,AT1受体阻断剂Valsartan明显抑制AngⅡ的这种促进作用,AT2受体拮抗剂PD123319明显增强AngⅡ的这种作用。结论增生性瘢痕成纤维细胞表达AT1和AT2受体,AngⅡ通过激活AT1和AT2受体对成纤维细胞的增殖产生调节作用,AngⅡ产生异常和受体表达比例失衡可能导致瘢痕的过度增生和瘢痕疙瘩的形成。

Role of angiotensin Ⅱ receptors in proliferation of fibroblast derived from human hypertrophic scars

OBJECTIVE: The present study was undertaken to observe the expression of angiotensin II (Ang II) type 1 (AT1) and type 2 (AT2) receptors in human hypertrophic scars, and explore their role in the proliferation of fibroblasts in human hypertrophic scars. METHODS: The expression of both ATL and AT2 receptors in fibroblasts of hypertrophic scars was detected with immunohistochemical staining. Radioligand receptor binding assay and RT-PCR were used to determined expression level of AT1 and AT2 receptors in cultured fibroblasts derived from hypertrophic scars. DNA synthesis was examined in cultured fibroblasts of hypertrophic scars by measuring 3H]-TdR incorporation into fibroblasts. RESULTS: Positive staining signals of both AT1 and AT2 receptors were found in fibroblasts of hypertrophic scars. Expression level of AT1 and AT2 receptors were (10.69 +/- 2.15) fmol/10(6) cells, (4.9 +/- 1.05) fmol/10(6) cells respectively in cultured fibroblasts derived from hypertrophic scars. RT-PCR showed the similar results. In cultured fibroblasts, Ang II stimulation significantly increased DNA synthesis (P < 0.05 vs negative control), which was inhibited by valsartan, an AT1 receptor blocker, but augmented by PD123319, an AT2 receptor antagonist. Valsartan or PD123319 alone did not influence the proliferation of fibroblasts derived from hypertrophic scars. CONCLUSIONS: Both AT1 and AT2 receptors were expressed in the fibroblasts of hypertrophic scars, and Ang II regulates DNA 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. The present study provides new insight into pathogenesis of hypertrophic scars.