Restivo Terry E, Mace Kimberly A, Harken Alden H, Young David M
Department of Surgery, University of California San Francisco-East Bay, Oakland, California, USA.
J Trauma. 2010 Aug;69(2):392-8. doi: 10.1097/TA.0b013e3181e772b0.
CXCL12 is a chemokine involved in postinjury leukocyte chemotaxis, migration, and homing of stem cells. We hypothesized that by increasing the level of the chemokine CXCL12 in wounds of diabetic mice, we would increase stem cell recruitment to the wound and, thus, accelerate time to wound closure.
Eighteen Lepr db-/db- (B6.Cg-m +/+ Leprdb/J; Jackson Labs, Bar Harbor, ME) and their nondiabetic littermates were wounded and treated either with an empty plasmid or a plasmid containing the CXCL12 gene. Wounds were measured approximately every 5 days until they closed completely and were analyzed using planimetry. Wounds were harvested, and relative expression of CXCL12 mRNA was measured using an ABI Prism SDS 7000. To study stem cells affected by this, the plasmid's affect on stem cell recruitment, we used flow cytometry.
The diabetic wounds contain a significantly decreased level of CXCL12 mRNA at day 7 postwounding, and these wounds take 55 days to heal. Application of a CXCL12 plasmid to diabetic wounds significantly increases CXCL12 mRNA at day 7, and these wounds heal in 23 days.
Lack of CXCL12 in diabetic wounds contributes to delayed wound healing and can be reversed via single application of a CXCL12-containing plasmid.
CXCL12是一种趋化因子，参与损伤后白细胞的趋化作用、迁移以及干细胞的归巢。我们推测，通过提高糖尿病小鼠伤口中趋化因子CXCL12的水平，能够增加干细胞向伤口的募集，从而加速伤口愈合时间。
选取18只Lepr db-/db-（B6.Cg-m +/+ Leprdb/J；杰克逊实验室，缅因州巴尔港）小鼠及其非糖尿病同窝仔鼠，对其进行创伤处理，并用空质粒或含CXCL12基因的质粒进行治疗。每隔约5天测量伤口大小，直至伤口完全愈合，并采用面积测量法进行分析。收集伤口组织，使用ABI Prism SDS 7000测定CXCL12 mRNA的相对表达量。为研究受此影响的干细胞以及质粒对干细胞募集的影响，我们采用了流式细胞术。
糖尿病伤口在创伤后第7天CXCL12 mRNA水平显著降低，这些伤口需要55天才能愈合。将CXCL12质粒应用于糖尿病伤口，可使第7天的CXCL12 mRNA显著增加，这些伤口在23天内愈合。
糖尿病伤口中CXCL12的缺乏导致伤口愈合延迟，通过单次应用含CXCL12的质粒可使其逆转。
