高迁移率族蛋白 B1（HMGB1）在创伤愈合中的作用。

Role of high mobility group box 1 (HMGB1) in wound healing.

机构信息

Department of Surgery, Sinai Hospital of Baltimore, Baltimore, Maryland, USA.

出版信息

J Surg Res. 2012 Jul;176(1):343-7. doi: 10.1016/j.jss.2011.06.069. Epub 2011 Jul 29.

DOI:10.1016/j.jss.2011.06.069

PMID:21872885

Abstract

BACKGROUND

HMGB1, a non-histone chromosomal protein, can bind to the receptor for advanced glycation end products (RAGE) and act as an inflammatory mediator. We examined the role of HMGB1 in incisional wound healing and its possible mechanism of action through receptor for advanced glycation end products (RAGE).

METHODS

Male Sprague-Dawley rats undergoing full-thickness incisional wounding with subcutaneous implantation of PVA sponges were given daily injections of ethyl pyruvate (EP) (40 mg/kg, i.p.), a potent inhibitor of HMGB1 release. At 7 d post-wounding, wound breaking strength, sponge collagen content, and wound fluid HMGB1 levels were assessed. In vitro rat dermal or wound-derived fibroblasts were cultured with recombinant HMGB1 or advanced glycation end product (AGE). Some cultures were co-treated with a RAGE-blocking antibody. Fibroblast proliferation and collagen synthesis were assayed.

RESULTS

In vivo treatment with EP significantly decreased wound HMGB1 levels (P < 0.05), which was paralleled by increased wound breaking strength (P < 0.05) and wound collagen content (P < 0.05). In vitro treatment with HMGB1 (100 ng/mL) had no effect on fibroblast proliferation but significantly reduced collagen synthesis (P < 0.05). This effect was abrogated by co-treatment with anti-RAGE antibody. Fibroblasts treated with AGE had lower collagen synthesis (P < 0.01), which was restored by anti-RAGE antibody treatment.

CONCLUSION

HMGB1 impairs fibroblast collagen synthesis. Reducing wound HMGB1 levels lead to increased tensile strength and collagen synthesis. The data suggest that HMGB1 affects collagen synthesis through activation of RAGE.

摘要

背景

高迁移率族蛋白 B1（HMGB1）是一种非组蛋白染色体蛋白，可与晚期糖基化终产物受体（RAGE）结合，作为炎症介质发挥作用。我们通过晚期糖基化终产物受体（RAGE）研究了 HMGB1 在切口愈合中的作用及其可能的作用机制。

方法

接受全层切口创伤并皮下植入 PVA 海绵的雄性 Sprague-Dawley 大鼠每天接受乙基丙酮酸（EP）（40mg/kg，腹腔内注射）注射，这是一种 HMGB1 释放的有效抑制剂。在创伤后 7 天，评估伤口破裂强度、海绵胶原含量和伤口液 HMGB1 水平。用重组 HMGB1 或晚期糖基化终产物（AGE）培养体外大鼠真皮或伤口来源的成纤维细胞。一些培养物与 RAGE 阻断抗体共同处理。测定成纤维细胞增殖和胶原合成。

结果

体内用 EP 治疗显著降低了伤口 HMGB1 水平（P<0.05），同时伤口破裂强度（P<0.05）和伤口胶原含量增加（P<0.05）。体外用 HMGB1（100ng/mL）处理对成纤维细胞增殖没有影响，但显著降低了胶原合成（P<0.05）。该作用可通过与抗 RAGE 抗体共同处理而被消除。用 AGE 处理的成纤维细胞胶原合成减少（P<0.01），用抗 RAGE 抗体处理后可恢复。