CGRP在糖尿病足神经与骨膜中的表达及其对破骨细胞分化及金属蛋白酶表达的影响

【摘要】〓目的〓研究降钙素基因相关肽(CGRP)在糖尿病足神经与骨膜中的表达及其对破骨细胞分化及金属蛋白酶(MMPs)表达的影响。方法〓取糖尿病足截肢病人与车祸导致截肢病人组织作CGRP免疫组化,以了解其在糖尿病足周围神经与跟骨骨膜中的表达。用CGRP处理RAW264.7培养体系,了解其对破骨细胞分化及金属蛋白酶表达的影响。结果〓糖尿病足周围神经纤维与骨膜组织中CGRP表达下降,CGRP可抑制RAW264.7细胞向破骨细胞分化及抑制,MMP-3,MMP-9的表达。结论〓糖尿病周围神经病变导致的CGRP水平的下降,可使破骨细胞的活化与MMPs的表达失去调节,与异常的骨破坏和难治性溃疡有着密切的关系,在糖尿病足的发病机制中起着重要作用。

The expression of CGRP in nerve fiber and periosteum of diabetic foot and its effects on osteoclasts differentiation and MMPs expression

Objective To detect the expression of calcitonin gene-related peptide （CGRP） in nerve fiber and periosteum of diabetic foot and its effects on osteoclasts differentiation and Metal Matrix Proteinases （MMPs） expression. Methods Immunohistochemical staining was utilized to detect the expression of CGRP in nerve fibers and periosteum of diabetic foot patients and traumatic amputees （as controls）. RAW 264.7 cells were treated with CGRP to study its effects on osteoclasts differentiation and MMPs expression.TRAP staining was used to determine osteoclasts and western-blot was utilized to detect the expression of MMP-2, MMP-3 and MMP-9. Results The expression of CGRP in nerve fibers and periosteum was deceased in Diabetic foot patients.CGRP inhibited the differentiation of osteoclasts and decreases the expression of MMP-3 and MMP-9. Conclusion The decreased CGRP in diabetic foot can result to MMPs over-expression of osteoclasts due to activation,leading to bone destruction and refractory foot ulceration and may play an important role in the pathogenesis of diabetic foot.