缺氧诱导因子-1α与血管内皮生长因子及其受体2在大鼠3期压力性损伤皮肤组织中的表达及意义*

doi:10.12047/j.cjap.5730.2019.043

摘要/Abstract

摘要： 目的:分析缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)和血管内皮生长因子受体2(KDR)在不同受压时间点大鼠压力性损伤局部皮肤组织中的表达及相互关系,探讨3期压力性损伤慢性难愈的可能机制。方法:将40只SD雄性大鼠随机分为正常对照组、受压3 d、5 d、7 d、 9 d组( n=8 ),使用磁铁压迫法建立3期压力性损伤动物模型。HE染色观察皮肤组织形态;免疫组化法检测VEGF表达,Western blot 检测皮肤组织HIF-1α、VEGF、KDR蛋白表达;对数据行单因素方差分析、LSD检验。结果:①HE结果显示,与正常对照组相比,受压组大鼠表皮逐渐增厚,血管数量不断减少,胶原排列紊乱,炎症细胞浸润增加。②免疫组化结果显示:受压3 d组大鼠皮肤组织中VEGF蛋白表达量较正常对照组明显增高(P＜0.01);受压5 d、7 d和 9 d组大鼠皮肤组织中VEGF蛋白表达量均明显低于正常对照组(P＜0.05)。WB结果和免疫组化结果一致。③WB结果显示:受压3 d、5 d和7 d组大鼠皮肤组织中HIF-1α表达量均明显高于正常对照组(P＜0.01 或 P＜0.05);4组受压组大鼠皮肤组织KDR蛋白表达量均低于正常对照组(P＜0.05或P＜0.01)。结论:HIF-1α介导的VEGF和KDR蛋白表达减少引起组织血管生成减少可能是3期压力性损伤慢性难愈的重要原因之一。

关键词: 缺氧诱导因子-1α, 血管内皮生长因子, 血管内皮生长因子受体2, 大鼠, 压力性损伤

Abstract: Objective: To analyze the expression and relationship of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR) in local skin tissues of pressure injury and investigate the possible mechanism of stage 3 pressure injury refractory wound.Methods: Forty male SD rats were randomly divided into normal control group, compressed 3 d, 5 d, 7 d, and 9 d groups. Stage 3 pressure injury animal model were established by magnet compression. The morphology of skin was observed by HE staining. The expression of VEGF was detected by immunohistochemistry. The expression levels of HIF-1α, VEGF and KDR protein in skin tissue were detected by Western blot. One-way analysis of variance and LSD test were performed on the data. Results: ①The HE results showed that compared with the normal control group, the epidermis of the compressed group was gradually thickened, the number of blood vessels was decreased, the collagen arrangement disordered and inflammatory cells infiltration were increased. ②Immunohistochemical results showed that the expression of VEGF protein in the 3 d group was significantly higher than that in the normal control group (P＜0.01). The expression of VEGF protein in the skin tissue of 5 d, 7 d and 9 d groups was lower than that in normal control group (P＜0.05). WB results were consistent with immunohistochemistry results. ③WB results showed that the expression of HIF-1α in the skin tissues of the rats in 3 d, 5 d and 7 d groups was higher than that in the normal control group (P＜0.01 or P＜0.05). The expression of KDR protein was lower than that of the normal control group (P＜0.05 or P＜0.01). Conclusion: HIF-1α mediated reduction of VEGF and KDR protein expression and decreased tissue angiogenesis may be one of the important causes of chronic dysfunction of stage 3 pressure injury.

Key words: hypoxia-inducible factor-1α, vascular endothelial growth factor, vascular endothelial growth factor receptor 2, rats, pressure injury

王晓慧, 陈孝萍, 王红萍, 潘莹莹, 姜丽萍. 缺氧诱导因子-1α与血管内皮生长因子及其受体2在大鼠3期压力性损伤皮肤组织中的表达及意义^*[J]. 中国应用生理学杂志, 2019, 35(3): 199-203.

WANG Xiao-hui, CHEN Xiao-ping, WANG Hong-ping, PAN Ying-ying, JIANG Li-ping. Expression and significance of hypoxia-inducible factor-1α and vascular endothelial growth factor and receptor 2 in stage 3 pressure injury of rats[J]. CJAP, 2019, 35(3): 199-203.

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缺氧诱导因子-1α与血管内皮生长因子及其受体2在大鼠3期压力性损伤皮肤组织中的表达及意义^*

Expression and significance of hypoxia-inducible factor-1α and vascular endothelial growth factor and receptor 2 in stage 3 pressure injury of rats

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