Effects of combined radiation and burn injury on the renin-angiotensin system.

Effects of combined radiation and burn injury on the renin-angiotensin system.
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DOI:
10.1111/j.1524-475x.2012.00867.x
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发表时间:
2013-01
期刊:
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
影响因子:
--
通讯作者:
Rodgers KE
Rodgers KE
中科院分区:
其他
文献类型:
--
作者:
Jadhav SS;Sharma N;Meeks CJ;Mordwinkin NM;Espinoza TB;Roda NR;DiZerega GS;Hill CK;Louie SG;Rodgers KE

文献摘要

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肾素血管紧张素系统(RAS)在伤口修复中发挥重要作用;然而,对于热和辐射加烧伤(CRBI)组合反应中的 RAS 表达知之甚少。本研究的目的是检验以下假设:热损伤会改变 RAS 成分的表达,而 CRBI 会延迟 RAS 的这种上调。将未受伤小鼠的皮肤与受到局部热损伤或 CRBI(损伤部位)的小鼠进行比较。分析皮肤中 RAS 成分的基因和蛋白质表达。热损伤后 RAS 各种成分的表达最初增加。然而,在较高 CRBI 组中,AT1b(血管收缩,促增殖)AT2(血管舒张,分化)和 Mas(血管舒张,抗炎)基因表达最初下降。这与成纤维细胞和角质形成细胞中 AT1、AT2 和 MAS 蛋白表达的延迟和减少相对应。 RAS 受体阳性成纤维细胞和角质形成细胞的减少与胶原沉积和角质形成细胞浸润到受伤区域的减少相关,导致 CRBI 后上皮再形成的延迟。这些数据支持这样的假设:在辐射暴露后观察到的受试者中观察到的伤口愈合延迟可能部分是由于 RAS 表达减少所致。
The renin angiotensin system (RAS) plays an important role in wound repair; however, little is known pertaining to RAS expression in response to thermal and the combination of radiation plus burn injury (CRBI). The purpose of this study was to test the hypothesis that thermal injury modifies expression of RAS components and CRBI delayed this up-regulation of RAS. Skin from uninjured mice was compared to mice receiving local thermal injury or CRBI (injury site). Skin was analyzed for gene and protein expression of RAS components. There was an initial increase in the expression of various components of RAS following thermal injury. However, in the higher CRBI group there is an initial decrease in AT1b (vasoconstriction, pro-proliferative) AT2 (vasodilation, differentiation) and Mas (vasodilation, anti-inflammatory) gene expression. This corresponded with a delay and decrease in AT1, AT2 and MAS protein expression in fibroblasts and keratinocytes. The reduction in RAS receptor positive fibroblasts and keratinocytes correlated with a reduction in collagen deposition and keratinocyte infiltration into the wounded area resulting in a delay of re-epithelialization following CRBI. These data support the hypothesis that delayed wound healing observed in subjects following radiation exposure may be in part due to decreased expression of RAS.