生肌化瘀方对糖尿病大鼠皮肤溃疡组织中MMP-3及TIMP-1表达的影响

Effect of Shengji Huayu Recipe on the Expression of MMP-3 and TIMP-1 in Skin Ulcer Tissue of Diabetic Rats

目的探讨生肌化瘀方对糖尿病大鼠皮肤溃疡创面组织中基质金属蛋白酶-3(MMP-3)和基质金属蛋白酶组织抑制剂-1(TIMP-1)表达的影响效应。方法以糖尿病大鼠皮肤溃疡模型为研究对象,采用不同配伍比例的生肌化瘀方(生肌方与化瘀方分别按2∶1、1∶1和1∶2比例组合)进行干预,采用Western blot法检测皮肤溃疡组织中MMP-3蛋白表达,免疫组化法检测TIMP-1蛋白表达。结果在成模各时间点,各组糖尿病大鼠血糖水平差异无统计学意义(P>0.05),而与正常创面组比较显著升高(P<0.01)。创面面积处理前后差值方面,生肌化瘀3号方组、正常创面组均明显优于糖尿病溃疡模型组(P<0.05)。Western blot法检测结果显示:生肌化瘀2号方组MMP-3蛋白表达高于生肌化瘀3号方组(P<0.05)。免疫组化法检测结果显示:生肌化瘀2号方组TIMP-1蛋白的表达低于糖尿病溃疡模型组和生肌化瘀1号方组(P<0.05),生肌化瘀3号方组的表达高于生肌化瘀2号方组(P<0.01)。结论在创面修复早期,采用生肌化瘀3号方生肌方有利于促进创面愈合;在创面愈合晚期,采用生肌化瘀2号方可能有利于抑制病理性瘢痕的形成。

Objective To study the effect of Shengji Huayu Recipe（SHR）on the expression of MMP-3 and TIMP-1 in the skin ulcer tissue of diabetic rats. Methods The skin ulcer model was estab- lished in diabetic mice. Different compatibility proportions of SHR [the ratio of Shengji Recipe （S JR） to Huayu Recipe （HYR） =2： 1, 1：1, and 1：2, respectively] were used to intervene. The expression of MMP- 3 protein in the skin ulcer of diabetic rats was detected by Western blot method,and TIMP-1 protein was detected by immunohistochemical assay. Results At each time point, there was no statistical difference in the blood glucose level among groups （P 〉0.05）. But all of them increased significantly,when com- pared with those of the normal wound group （P 〈0.01 ）. As for the difference between after would area treatment and before would area treatment, better effect was obtained in the SHR No. 3 group and the normal ulcer group than in the diabetic ulcer model group （P 〈0.05）. Results of Western blot showed that the MMP-3 protein expression was higher in the SHR No. 2 group than in the SHR No.3 group （P 〈0.05）. Immunohistochemical results showed that TIMP-1 protein expression was lower in the SHR No. 2 group than in the SHR No.3 group and the diabetic ulcer model group （P 〈0.05）. TIMP-1 protein expression was higherin the SHR No. 3 group than in the SHR No.2 group （P 〈0.01）. Conclusion Using SHR No.3 was conducive to the promotion of wound healing in early wound repair stage, and using SHR No. 2 might beconducive to inhibiting the formation of pathological scar.