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深Ⅱ度烫伤大鼠创面基质金属蛋白酶-1,2及其抑制剂表达变化机制的探讨

The regulation mechanisms of MMP-1, 2 and TIMP-1,2 on wound healing after partial thickness scald

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【作者】 程飚付小兵顾小曼孙同柱孙晓庆盛志勇

【Author】 CHENG Biao, FU Xiao bing, GU Xiao man, SUN Tong zhu, SUN Xiao qing, SHENG Zhi yong. Key Laboratory of Wound Repair, 304th Hospital, People′s Liberation Army, Beijing 100037, China

【机构】 解放军第三四医院全军创伤修复重点实验室解放军第三四医院全军创伤修复重点实验室 100037北京100037北京

【摘要】 目的 观察深Ⅱ度烫伤创面愈合过程中基质金属蛋白酶 1,2 (MMP 1,2 )与金属蛋白酶组织抑制因子 1,2 (TIMP 1,2 )的表达规律以及其变化机制。 方法  150只Wistar大鼠 3 0 %深Ⅱ度烫伤后随机分为 5组 :(1)正常对照组 (n =6) ;(2 )单纯烫伤组 (n =3 6) ;(3 )激酶激活剂BDM组 (n =3 6) ;(4)蛋白激酶C制剂H7组 (n =3 6) ;(5)c fos抗体组 (n =3 6)。分别于伤后 3、6h和 1、3、7、14d采取创面皮肤标本 ,检测创面组织c fosmRNA与c fos蛋白的表达 ,以及MMP 1,2 /TIMP 1,2相应变化。 结果 伤后 3~ 6h ,c fosmRNA与c fos蛋白的表达明显增多 ,随后逐渐下降。MMP 1,2 /TIMP 1,2的表达滞后于前者 ,在伤后 3~ 7d表达较高 ,MMP 2 /TIMP 2的表达增加显著。使用BDM后 ,烫伤 3~6h组织c fosmRNA与c fos蛋白的表达增加 ,MMP 1,2 /TIMP 1,2的表达也增强。使用H7后 ,c fosmRNA与c fos蛋白的表达被抑制 ,MMP 1,2 /TIMP 1,2的表达随之减弱。c fos抗体中和内源性c fos蛋白表达后 ,MMP 1/TIMP 1,2的表达受抑制 ,MMP 2的变化不明显。 结论 创面愈合过程中 ,MMP 1,2和TIMP 1,2的表达与蛋白激酶信号途径的激活有密切关系 ,c fos调节MMP 1和TIMP 1和TIMP 2的含量 ,完成对愈合的调控。

【Abstract】 Objective To observe the changes of matrix metalloproteinase 1, 2/tissue inhibitor of metalloproteinase 1, 2 (MMP 1, 2 and TIMP 1, 2) in granulationtissue after 30% TBSA deeper partial thickness scald, and explore the regulation mechanism of MMP 2/TIMP 2 during wound healing. Methods 150 male Wistar rats were randomly divided into 5 groups as follows: (1) normal control (n=6); (2) injured control group (n=36): which is subdivided into postburn 3 h, 6 h, 1 d, 3 d, 7 d and 14 d groups, respectively; (3) BDM group (n=36): intravenous injected of 400 mg 2,3 butanedione monoxime in each rat was done after anesthesia;(4) H7 group (n=36): Each rat was intravenous injected of 0 2 mg 1 5 isoquinolinyl sulfony 2 methylpiperazine after anesthesia;(5) anti c fos group (n=36): Each rat was intravenous injected of 5 μg c fos monoclony antibody after anesthesia. The immunohistochemistry staining technique and the reverse transcription polymerase chain reaction (RT PCR) were used for detectting. Results The expression of c fos mRNA and protein was increased from 3 to 6 hours post burn, and then decreased. The expression of MMP 1, 2/TIMP 1, 2 was delayed to 3 days post burn compared with the expression of c fos mRNA and protein. Treatment with BDM induced to raise c fos mRNA and protein expression. The expression of MMP 1, 2/TIMP 1, 2 was also increased accordingly. However, following treatment with H7 inhibited the expression of c fos mRNA and protein, MMP 1, 2/TIMP 1, 2 proteins expression decreased. Exogenous c fos antibody could inhibit endogenous c fos protein expression and the expression of MMP 1/TIMP 1, 2 decreased, but MMP 2 has no notable changes. Conclusions The expression of MMP 1, 2 and TIMP 1, 2 has closely relation protein kinases activated signaling pathways. The expression changes of MMP 1 and TIMP 1/ TIMP 2 depend on c fos expression. Oncogenes play an important role in the change process of wound matrix degradation and remodeling.

【基金】 国家重大基础研究规划资助 (G1 9990 542 0 4 );国家自然科学基金资助 (No .30 1 70 96 6 );国家杰出青年科学基金资助 (No .3952 50 2 4 );博士后基金(中博基 [2 0 0 1 ]No .1 4)
  • 【文献出处】 中华外科杂志 ,Chinese Journal of Surgery , 编辑部邮箱 ,2003年10期
  • 【分类号】R644
  • 【被引频次】6
  • 【下载频次】111
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