Schreiber Jeffrey, Efron Philip A, Park Julie E, Moldawer Lyle L, Barbul Adrian
Department of Surgery, Sinai Hospital of Baltimore and the Johns Hopkins Medical Institutions, Baltimore, MD 21215, USA.
Surgery. 2005 Nov;138(5):940-6. doi: 10.1016/j.surg.2005.05.020.
The transcription factor nuclear factor-kappaB (NF-kappaB) plays an essential role in inflammation. To date, no studies have investigated the effect of inhibiting NF-kappaB-mediated inflammation on normal cutaneous wound healing. We tested this by locally administering an adenovirus recombinant that constitutively expresses a super-repressor isoform of inhibitory-kappaB (IkappaB) into rats undergoing a well-established model of dorsal wound healing.
Seventy-two Sprague-Dawley rats underwent insertion of a sponge-pump construct into a dorsal subcutaneous pocket. One group of rats received pumps filled with the adenovirus expressing I-kappaB (rAd-Ikappab), a second group received pumps filled with adenovirus expressing green fluorescent protein (GFP) (rAd-gfp), and a third received pumps filled with normal saline (NS). Rats were killed in groups of 6 on days 1, 3, 5 and 7 postoperation. The wound fluid was analyzed for nitrite/nitrate (NOx) and tumor necrosis factor-alpha (TNF-alpha) concentrations. The wound fluid was assayed for hydroxyproline (OHP) content, an index of reparative collagen deposition.
Administration of rAd-Ikappab for 7 days resulted in higher collagen deposition (OHP) compared with the rAd-gfp and NS groups. NOx levels were significantly higher in the rAd-gfp group on day 1 and marginally so on day 5. TNF-alpha quantitation analysis found no significant difference among the 3 groups.
IkappaB expression through an adenoviral vector in the cutaneous wound may improve rodent healing, as shown by increased collagen deposition, through decreased inflammation. This mechanism appears to be TNF-alpha independent. Inhibition of NF-kappaB may reduce inflammation by reducing the local NOx concentrations.
转录因子核因子-κB（NF-κB）在炎症反应中起关键作用。迄今为止，尚无研究探讨抑制NF-κB介导的炎症对正常皮肤伤口愈合的影响。我们通过向建立良好的背部伤口愈合模型大鼠局部注射组成型表达抑制性κB（IkappaB）超抑制异构体的腺病毒重组体来对此进行测试。
72只Sprague-Dawley大鼠在背部皮下囊袋植入海绵泵装置。一组大鼠接受填充有表达I-κB的腺病毒（rAd-Ikappab）的泵，第二组接受填充有表达绿色荧光蛋白（GFP）的腺病毒（rAd-gfp）的泵，第三组接受填充有生理盐水（NS）的泵。术后第1、3、5和7天，每组6只大鼠处死。分析伤口渗出液中的亚硝酸盐/硝酸盐（NOx）和肿瘤坏死因子-α（TNF-α）浓度。检测伤口渗出液中的羟脯氨酸（OHP）含量，这是修复性胶原蛋白沉积的一个指标。
与rAd-gfp组和NS组相比，给予rAd-Ikappab 7天导致更高的胶原蛋白沉积（OHP）。rAd-gfp组第1天的NOx水平显著更高，第5天略有升高。TNF-α定量分析发现3组之间无显著差异。
如通过增加胶原蛋白沉积所示，在皮肤伤口中通过腺病毒载体表达IkappaB可通过减轻炎症来改善啮齿动物的愈合。这种机制似乎不依赖TNF-α。抑制NF-κB可能通过降低局部NOx浓度来减轻炎症。
