Inhibition of tissue transglutaminase and ɛ (γ‐glutamyl) lysine cross‐linking in human hypertrophic scar
Inhibition of tissue transglutaminase and ɛ (γ‐glutamyl) lysine cross‐linking in human hypertrophic scar
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DOI：
10.1046/j.1524-475x.1996.40105.x
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发表时间：
1996-01
影响因子：
2.9
通讯作者：
K. Dolynchuk
中科院分区：
文献类型：
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作者：
K. Dolynchuk
用抗组织转氨酶单克隆抗体进行免疫组织化学染色，研究人皮肤伤口的低温切片。该酶在急性创伤和慢性增生性瘢痕中发现，但在正常成熟瘢痕中没有发现。由于组织转氨酶负责异肽交联的形成，因此使用两阶段高效液相色谱分析来定量各种类型伤口组织产生的γ-谷氨酰赖氨酸交联。18例损伤后6个月至10年的增生性瘢痕患者接受了一项双盲试验，在非封闭性敷料（Biofill）下使用腐胺50 mmol/L共晶溶剂治疗2个月。对于相同或不同瘢痕的对照部分，同时应用假溶剂和非封闭性敷料。2个月后，在活检或择期翻修手术时采集两处瘢痕。在均质化和彻底蛋白水解后，使用高效液相色谱分析研究酶。治疗的结果是异肽交联形成水平从未治疗瘢痕中的0.018 ± .006 nmol/µmol氨基酸显著降低至治疗组中的0.008 ± .001 nmol/µmol氨基酸（p < 0.05）。治疗瘢痕中的异肽交联含量几乎与正常成熟瘢痕中的含量一样低（0.003 ± 0.001 nmol/µmol氨基酸）。这些结果表明，在腐胺治疗增生性瘢痕期间，组织转氨酶活性引起的交联形成受到抑制。这些结果支持局部腐胺在治疗增生性瘢痕形成中的可能治疗用途。
Immunohistochemical staining with monoclonal antibody to tissue transglutaminase was used to study cryostat sections of human skin wounds. The enzyme was found in acute wounds and chronic hypertrophic scars but not in normal mature scars. Because tissue transglutaminase is responsible for the formation of isopeptide cross‐links, a two‐stage high‐performance liquid chromatographic analysis was used to quantitate the ɛ (γ‐glutamyl) lysine cross‐link produced by various types of wound tissues. Eighteen patients with hypertrophic scars between 6 months' and 10 years' duration after injury underwent a double‐blind trial with putrescine 50 mmol/L in a eutectic vehicle for 2 months under nonocclusive dressings (Biofill). For the control portion of the same or different scar, sham vehicle and non‐occlusive dressing were simultaneously applied. Both scars were harvested at biopsy or elective revision surgery 2 months later. After homo‐genization and exhaustive proteolysis, digests were studied with the use of high‐performance liquid chromatography analysis. The results of treatment were a significant decrease in the levels of isopeptide cross‐link formation from 0.018 ± .006 nmol/µmol amino acids in untreated scars to 0.008 ± .001 nmol/µmol amino acid in the treated group (p < 0.05). The isopeptide cross‐link content in treated scars was nearly as low as that in normal mature scars (0.003 ± 0.001 nmol/µmol amino acid). These results show that cross‐link formation by tissue transglutaminase activity is inhibited during treatment of hypertrophic scar by putrescine. These results support the possible therapeutic use of topical putrescine in the treatment of hypertrophic scar formation.