扁平苔藓皮损中缺氧诱导因子1α、血管内皮生长因子和蛋白激酶B的表达

Expression of hypoxia-inducible factor 1α, vascular endothelial growth factor and protein kinase B in lichen planus lesions

目的探讨扁平苔藓皮损中缺氧诱导因子1α（HIF—1α）、血管内皮生长因子（VEGF）和蛋白激酶B（P-Akt）的表达与血管形成及凋亡的关系。方法免疫组化法和TUNEL法检测32例扁平苔藓患者皮损和20例脂肪瘤皮肤石蜡标本HIF—1α、VEGF和P—Akt表达和细胞凋亡情况，同时用CD34标记血管内皮细胞，计算微血管密度（MVD）。结果HIF-1α、VEGF和P—Akt在32例扁平苔藓组皮损表皮角质形成细胞中均有不同程度的表达（＋＋-＋＋＋），HIF-1α表达部位为细胞核，VEGF和P-Akt表达部位为细胞质，高于对照组HIF-1α、VEGF和P-Akt（-～＋＋）的表达，两组比较，差异有统计学意义（均P〈0．01）。扁平苔藓组皮损处MVD为（21．27±6．54）个／高倍视野（×200），对照组MVD为（10．26±1．10）个／高倍视野（×200），两组比较，差异有统计学意义（t=5．607，P〈0．01）。扁平苔藓组表皮层角质形成细胞的凋亡指数（72．81％±9．234％）显著高于对照组（28．16％±3．464％），两组比较，差异有统计学意义（t=8．431，P〈0．01）。扁平苔藓皮损中HIF-1α、VEGF和P—Akt的表达水平间均呈正相关（r值分别为0．625，0．453，0．455，均P〈0．01）。HIF-1α、VEGF和P—Akt的表达与MVD均呈正相关（r值分别为0．721，0．646，0．671，均P〈0．01）。结论HIF-1α及其下游靶基因VEGF、P—Akt在扁平苔藓的发病中可能起一定的作用。

Objective To explore relationships of expression of hypoxia-inducible factor-1α （HIF- 1α）, vascular endothelial growth factor （VEGF） and protein kinase B （P-Akt） with angiopoiesis and cell apoptosis. Methods Biopsy specimens were collected from skin lesions of 32 patients with lichen planus and normal skin of 20 patients with lipomyoma, and subjected to paraffin embedding, hnmunohistochemical staining was performed to measure expression of HIF-1α, VEGF and P-Akt, and TUNEL technique was used to detect apoptosis of keratinocytes in these paraffin-embedded tissue sections. Microvessel density （MVD） was assessed by counting CD34-1abeled vascular endothelial cells. Results HIF-1α VEGF and P-Akt were moderately or strongly expressed in lichen planus lesions, but absent or weakly expressed in normal skin of controls, and the expression of HIF- 1α, VEGF and P-Akt was significantly higher in the lichen planus group than in the control group （all P 〈 0.01）. HIF-1α was mainly expressed in nuclei of keratinocytes, while VEGF and P-Akt were expressed in the cytoplasm of keratinocytes. In addition, the lichen planus group showed significantly increased MVD （21.27 ± 6.54 vs. 10.26±1.10 microvessels/highpower （200 × ） field, t = 5.607, P 〈 0.01） and apoptosis rate of keratinocytes （72.81%± 9.234% vs. 28.16%±3.464%, t = 8.431, P 〈 0.01） compared with the eontrol group. Pearson eorrelation analysis showed that there were positive correlations between HIF-1α and VEGF expression, between VEGF and P- Akt expression, and between P-Akt and HIF-1α expression in the lichen planus group （r = 0.625, 0.453, 0.455, respectively, all P 〈 0.01 ）, and expression of HIF-1α, VEGF and P-Akt was all positively correlated with MVD （r = 0.721, 0.646, 0.671, respectively, all P 〈 0.01）. Conclusion HIF-1α and its downstream target genes VEGF and P-Akt may play a certain role in the occurrence of lichen planus.