创面修复中PDGFβ受体拮抗剂对周细胞血管生成的影响  

The effect of PDGFRβ antagonist on regulating the angiogenesis of pericytes in wound healing

作　　者：孙慧勤[1] 肖生强[1] 杨涛[1] 郝娜[2] 郭徳玉 周青[1] 粟永萍[1] 冉新泽[1] 

机构地区：[1]第三军医大学预防医学院全军复合伤研究所,创伤,烧伤与复合伤国家重点实验室,重庆市纳米医药工程技术研究中心,重庆400038 [2]第三军医大学护理学院基础护理学教研室,重庆400038 [3]第三军医大学西南医院病理学研究所,重庆400038

出　　处：《成都医学院学报》2012年第1期6-10,21,共6页Journal of Chengdu Medical College

基　　金：全军十一五医药卫生科研基金(No:06H030);创伤;烧伤与复合伤国家重点实验室开放基金(2006年度A类);国家自然科学基金(No:30971141)

摘　　要：目的研究PDGFRβ受体拮抗剂-甲磺酸伊马替尼(imatinib mesylate,75mg/kg)阻断PDGFβ受体通路对周细胞的调控在创面修复特别是肉芽组织血管生成中的作用。方法采用大体观测、组织学及免疫组化结合形态定量分析方法,研究PDGFβ受体阻断后创面愈合情况,并着重观测早期1～10d肉芽组织血管生成过程中微血管形态、密度,周细胞标记指数状况,分析周细胞变化与血管生成、创面愈合之间的关系以及与创面修复改变的联系与规律。结果对照组创面10d左右愈合,12d完全愈合,而甲磺酸伊马替尼组愈合时间延长多至14d,17d完全愈合,与对照相比延迟4～5d;创面残留面积伤后1d起与对照组比较存在差异(P<0.05)并见于主要观测点。致伤后创面修复组织病理变化呈现炎症、肉芽组织增生和瘢痕形成改变,其中的血管生成及周细胞主要见于肉芽组织增生期(3～10d),以5、7d为明显;周细胞标记指数与微血管密度呈正相关,但甲磺酸伊马替尼组较对照组微血管密度、周细胞标记指数则明显降低(P<0.05),且微血管管腔较大,以肉芽组织较丰富的5、7d时为明显,并与周细胞标记指数相关。此外甲磺酸伊马替尼组肉芽组织内还呈现细胞(主要是成纤维细胞为主的梭形细胞)数目、形成的胶原纤维较对照组减少等变化。结论 PDGFβ及其受体通路在创面修复中具有重要作用,其中对周细胞的作用可能影响血管生成及胶原形成等过程延迟创面修复,提示周细胞是血管生成中的重要组分之一,而PDGFβ受体通路对周细胞具有特异的调控作用。Objective To understand the effect of PDGFI3 receptor pathway on the regulation of pericyte angiogenesis in wound healing,especially in the formation of granulation tissue. Methods The model of cutaneous wound of mouse was created by making full-thickness skin excision,and the PDGFRI3 receptor was blocked by the specific antagonist（imatinib mesylate, 75mg/kg i. p. ）. The area of residual wound and the time of wound healing, histological morphology,mean density of microvessel（MVD）as well as the labeling index of pericytes in microvessels were measured by quantification of histological, immunohistochemical and morphological assesses. Results The healing time of the Imatinib mesylate group was obviously delayed for 4 to 5 days compared with the control,and Imatinib mesylate treatment induced a significant greater of residual area of wound since day 1 （P〈0.05）. Various pathological changes in wound repair were demonstrated in all of the three phases of wound healing：hemostasis and inflammation,granulation tissue formation and remodeling. The angiogenesis and pericytes were manifested in the phase of granulation tissue proliferation（3-10 days）,especially at day 5 and 7. The labeling index of pericytes（MPN） was positively correlated with MVD, but compared with the control group, the MVD and MPN of the Imatinib mesylate group was decreased（P〈0.05） ,and accompanied with wider vessel lumen. The number of spindle ceils and deposited collagen fibrils in the granulation tissue in Imatinib treated mice were decreased at the same time. Conclusions Blocking PDGF~ receptor pathway resulted in delayed wound healing with decreased perieytes and microvessels,suggesting that pericyte was play a significance role in angiogenesis mediated by PDGFβ/PDGFRβ pathway.

关 键 词：周细胞 血管生成 PDGFβ受体通路 创面修复 

分 类 号：R602[医药卫生—外科学]