APG治疗糖尿病难治性皮肤溃疡对创面肉芽组织中MMP-1、MMP-9及TIMP-1水平的影响  

Dynamic Changes of MMP-1,MMP-9 and TIMP-1 in the Refractory Diabetic Dermal Ulcers Treated by Autologous Platelet-rich Gel

作　　者：何利平[1,2,3] 王椿[1,2] 陈大伟[1,2] 李秀钧[1,2] 冉兴无[1,2] 

机构地区：[1]四川大学华西医院糖尿病足诊治中心,成都610041 [2]四川大学华西医院内分泌代谢科,成都610041 [3]重钢总医院老年科

出　　处：《四川大学学报（医学版）》2012年第5期757-761,共5页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(No.81170776/H0713);四川省科技厅科技支撑项目(2009sz0153)资助

摘　　要：目的探讨自体富血小板凝胶(APG)治疗糖尿病难治性皮肤溃疡过程中,溃疡肉芽组织中基质金属蛋白酶(MMP)-1、-9及基质金属蛋白酶抑制因子-1(TIMP-1)的动态变化。方法 86例糖尿病皮肤溃疡患者随机分为标准治疗组(单用溃疡标准治疗)或APG治疗组(标准治疗基础上加APG治疗)。APG组治疗前和治疗后3、6、9、15d及标准治疗组治疗前和治疗后6、15d时采集创面肉芽组织,其中21例患者完整获取观察各时间点肉芽组织纳入最后分析,APG组12例,标准治疗组9例。用酶联免疫法检测肉芽组织中MMP-1、MMP-9和TIMP-1浓度,同时观察溃疡愈合情况。结果 APG治疗组溃疡面积在各观察时间点较治疗前缩小(P<0.05);该组肉芽组织MMP-1浓度呈现波动变化,在治疗后第15d时降至最低(vs.6d,P<0.05);MMP-9从治疗后第3d起逐渐降低,但各时点与治疗前相比,差异均无统计学意义;TIMP-1在治疗后第3d开始增高,第6d达到最高(P<0.05);MMP-9/TIMP-1比值在治疗后的第6、15d均较治疗前下降(P<0.01)。标准治疗组溃疡面积在治疗后第15d时较治疗前及治疗后第6d缩小(P<0.05);该组肉芽组织MMP-1浓度第6d明显升高(P<0.05),于第15d降低但仍高于APG组(P<0.05);MMP-9浓度第15d时较治疗前降低(P<0.05);TIMP-1的浓度治疗前后差异均无统计学意义;MMP-9/TIMP-1比值第15d较治疗前降低(P<0.05)。MMP-9/TIMP-1比值与溃疡面积大小呈正相关(r=0.353,P<0.05)。结论 APG治疗可降低糖尿病难治性皮肤溃疡肉芽组织中MMPs的浓度,同时提高TIMPs浓度,进而改善局部MMPs-TIMPs平衡;MMP-9/TIMP-1比值是影响糖尿病难治性皮肤溃疡愈合的相关因素。Objective To investigate the dynamic changes of matrix metalloproteinase-1,-9 （MMP-1,MMP- 9） and tissue inhibitor of metalloproteinase-I （TIMP-1） in the refractory diabetic dermal ulcers treated with autologous platelet-rich gel （APG）. Methods 86 patients with nonhealing diabetic dermal ulcers were randomly assigned to two groups treated with standard procedures and APG （standard care plus topic application of autologous platelet-rich gel）. The granulation tissues were collected at d0, d3, d6, d9, and d15 in patients in the APG group and at dO, d6, d15 in patients in the standard care group. The areas of ulcers were measured. The protein levels of MMP-1, MMP-9 and TIMP-1 in the tissues were determined with ELISA. The ratio of MMP-9/TIMP-1 and its relationship with the areas of ulcers were examined. Results The areas of ulcers of patients in the APG group decreased significantely （vs. do, P〈0.05）. The concentrations of MMP-1 in the granulation tissues of patients treated with APG fluctuated and reached the lowest level at d15 （vs. d6, P〈0.05）. The concentrations of MMP-9 in the patients treated with AGP decreased from d3 to d15, but without statistical significance compared with d0 （P〉0.05）. The concentrations of TIMP-1 in the patients treated with AGP increased from d3 and reached the peak at d6 （P〈0.05）. The ratio of MMP-9/TIMP-1 at both d6 and d15 decreased significantly compared with dO （P〈 0.05） in the patients treated with AGP. The areas of ulcers in the patients with standard care decreased significantly at d15 （vs. d6,P〈0.05）. The concentrations of MMP-1 reached the peak at d6 （P〈0.05） and then decreased inthe patients with standard care but was still higher than the patients treated with APG （P 〈 0.05）. The concentrations of MMP-9 decreased significantly at d15 compared with dO in the patients treated with standard care （P〈0. 05）, but the change of TIMP-1 was not significant. The ratio of MMP-9/TIMP-1 in the patients with standard care

关 键 词：自体富血小板凝胶 糖尿病 难治性皮肤溃疡 基质金属蛋白酶 基质金属蛋白酶抑制因子 

分 类 号：R587.2[医药卫生—内分泌] R632.1[医药卫生—内科学]